European Journal of Medicinal Chemistry 58 (2012) 418e430

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European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech

Original article

Synthesis and antiproliferative activity of helonioside A, 30 ,40 ,60 -tri-Oferuloylsucrose, lapathoside C and their analogs
Parthasarathi Panda a, Manjuvani Appalashetti a, Meenubharathi Natarajan b, Chan-Park Mary a,
Subbu S. Venkatraman b, Zaher M.A. Judeh a, *
a
b

School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, N1.2-B1-14, Singapore 637459, Singapore
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, N4.1-02-06, Singapore 639798, Singapore

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 5 August 2012
Received in revised form
17 October 2012
Accepted 18 October 2012
Available online 27 October 2012

The first total synthesis of natural phenylpropanoid sucrose esters (PSEs) helonioside A 1, 30 ,40 ,60 -tri-Oferuloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSE analogs has been successfully
accomplished in a short and simple synthetic route. A selected set of 17 synthesized PSEs were evaluated
for the antiproliferative activity against human cervical epithelioid carcinoma (HeLa) cell lines using MTS
assay method. Eleven (11) compounds showed significant antiproliferative activity with their IC50values
ranging from 0.16 to 6.01 mM. The structureeactivity-relationship studies revealed that the antiproliferative activity is influenced by the lipophilicity and number of feruloyl substituents on these
compounds. The preliminary screening indicated that these compounds are potentially very valuable
source for new lead chemotherapeutics.
Ó 2012 Elsevier Masson SAS. All rights reserved.

Keywords:
Helonioside A, 30 ,40 ,60 -tri-O-feruloylsucrose
Lapathoside C
Phenylpropanoid sucrose esters
Antiproliferative activity
Isopropylidene acetal
Regioselective acylation
Sucrose esters
HeLa cells

1. Introduction
O-feruloylsucroses belong to an important class of phenylpropanoid sucrose esters (PSEs) and are found in various medicinal
plants with promising biological activities [1]. For example, helonioside A 1 (i.e. 30 ,60 -di-O-feruloylsucrose) (Fig. 1) was isolated
from the extracts of various liliaceous plants of Heloniopsis orientalis
[2], Smilax glabra [3], Smilax china [4], Trillium kamtschaticum [5],
Paris polyphylla var. yunnanensis [6,7], Smilacaceous plants of Smilax
bracteata [8] and Polygonaceous plants of Polygonum perfoliatum [9],
Bistorta manshuriensis [10] and Rumex dentatus [11]. The whole plant
P. polyphylla var. yunnanensis (Liliaceae) has been used in traditional
Chinese medicine to treat lung, liver and laryngeal carcinoma [6,12].
The extracts of H. orientalis displayed potent cytotoxicity against
lung carcinoma cell lines (A549) with IC50 value of 4.6 mg/mL and
colon carcinoma cell lines (Col2) with IC50 of 4.5 mg/mL [13]. The S.
china crude extracts were found to have antimutagenic activities
while its tuber showed significant cytotoxicity against various tumor

* Corresponding author. Tel.: þ65 6790 6738; fax: þ65 6794 7553.
E-mail address: zaher@ntu.edu.sg (Z.M.A. Judeh).
0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.ejmech.2012.10.034

cell lines [4,14]. Yan et al. reported that helonioside A 1 exhibited
cytotoxic effects in a dose-dependent manner against mice lung
adenocarcinoma cell line (LA 795) [6,7]. Helonioside A 1 also displayed potent antioxidant activity against stable DPPH-free radical
at a concentration of 0.02 mM [5]. 30 ,40 ,60 -tri-O-feruloylsucrose 2
(Fig. 1) was isolated from the ethanol extracts of the rhizomes and
roots of Smilax riparia [15]. Lapathoside C 3 (i.e. 6-mono-O-feruloyl30 ,60 -di-O-coumaroylsucrose) (Fig. 1) was isolated from the various
Polygonaceous plant species such as Polygonum lapathifolium [16],
Polygonum sachalinensis [17] and Polygonum cuspidatum [18]. The
Smilax genus of Liliaceous Plants and Polygonum genus of the Polygonaceous plants and their extracts are widely used in traditional
and folk medicines for the treatment of various disorders and
diseases such as cancer, tumors, jaundice, coughs, carbuncles,
dysentery ... etc. [1].
The entire published research in the area of PSEs focusses on the
extraction, characterization and biological screening of these
compounds [1,19e22]. With the exception of two reports [23,24],
the synthesis of this large class of compounds (about 150 natural
PSEs have been reported to date) has not been reported. In one of
these reports, our group has successfully demonstrated the
synthesis of lapathoside D and its analogs and reported their

for 3 days (Scheme 1). Herein.t.25].40 . 2. both as white solids. lapathoside C 3 and their analogs was attempted by regio. the di-acylated product 8 was found to be the major reaction product (44% yield) while the tri-acylated product 9 was obtained in 26% yield.6-di-O-isopropylidene sucrose 4 [24.60 tri-O-feruloylsucrose 2.3 mol equiv of p-acetoxyferuloyl chloride 5 (Scheme 1).25] was reacted with 1. In continuation to our on-going research efforts for developing practical and viable synthetic routes and exploring the potential of various PSEs as anticancer drug lead compounds [24]. 30 .2 mol instead of 1.2 mol equiv of p-acetoxyferuloyl chloride 5 at r. In order to prepare the tri-acylated compounds.and chemoselective acylation of di-O-isopropylidene 4 with p-acetoxyferuloyl chloride 5.1 equiv of p-acetoxyferuloyl chloride 5 [26] at r. helonioside A 1.4 mol equiv of Scheme 1. compound 6 was obtained as the major product in 31% yield along with compounds 8 (11% yield) and 9 (12% yield) as white solids. Structure of helonioside A 1. 30 .60 -tri-O-feruloylsucrose 2 and lapathoside C 3. Likewise. Attempts to increase the yield by varying the reaction conditions (time.40 . 2. 30 .60 -tri-O-feruloylsucrose 2.40 . reaction between 4. Clearly this result indicated that the use of 2.10 :4.1. Results and discussion 2.60 -tri-O-feruloylsucrose 2 and their analogs At the outset. we became interested in the synthesis of helonioside A 1. we report the first total syntheses of helonioside A 1. higher temperature) were not successful.P. di-O-isopropylidene sucrose 4 was reacted with 3. when di-O-isopropylidene sucrose 4 [24.1. . 30 .40 .60 -tri-O-feruloylsucrose 2. lapathoside C 3 and their analogs. Reaction of di-O-isopropylidene sucrose 4 with 2. Regio. antiproliferative activities [24].and chemoselective acylation of the versatile substrate 2.1. / European Journal of Medicinal Chemistry 58 (2012) 418e430 419 Fig. Panda et al. We also report on their antiproliferative activities against human cervical epithelioid carcinoma (HeLa) cell lines and examine the structural features that contribute to better activities. Interestingly. 30 .40 . Preparation of helonioside A 1. (Scheme 1) afforded compound 8 as the major product (30% yield) along with compound 6 in 3% yield.1 mol selectively gave the di-acylated product 8 over the monoacylated product 6. 1. lapathoside C 3 and their unnatural analogs. Chemistry The synthesis of the target compounds.t.

the HR-MS spectrum of compound 15 displayed m/z 973.6.40 .1 ppm (4  2 (CH3)2C) and 99. Next. 2 and 14.20e1. H-1100 for the COCH3).1. respectively. helonioside A 1. Furthermore.16 ppm.53 ppm (4 s. we can have the choice to prepare the mono-. di-. compounds 11e13 revealed the absence of the characteristic signals for the two isopropylidene moieties usually observed in the 1H NMR spectra at d 1.4e170.60 -tetraO-feruloylsucrose 14 were successfully obtained as white solids in 68%.40 .1 equiv) gave compound 18 (36% yield) along with compound 19 (7% yield) both as white solid (Scheme 2).and tetra-acylated compounds.7] (See Supporting information).26e2. (2) with the correct number of mole equiv of p-acetoxyferuloyl chloride 5. 30 . The typical value of the chemical shift of the anomeric (H-1) protons for compounds 11e13 shifted downfield at d 5. Preparation of lapathoside C and its analogs We have previously reported the successful synthesis of 30 . At this point. These results indicated: (1) the reactivity of the OH groups are in the order of 60 -OH > 30 -OH > 40 -OH > 3-OH. [26] demonstrated the successful deacetylation of a similar sugar. using piperidine-95% ethanol in good yield. The analysis data for 30 . The 1H and 13C NMR spectra of compound 15 revealed that the disappearance of the characteristic signals for the acetyl moieties at d 2. represented by the characteristic proton signals at d 2. Gladly. 65% and 76% yield. The HR-MS of helonioside A 1 showed m/z 717. 2) was confirmed by comparison to the data reported for the isolated natural product [2.2. The 1H and 13C NMR spectra of compounds 1. and (3) analogs (or unnatural O-feruloylsucroses) can easily be prepared by controlling the number and position of p-acetoxyferuloyl chloride 5.9 ppm (C-1100 for COCH3) and also carbonyl carbons at d 168.5e20. 2. In the same fashion. the structure of helonioside A 1 (Fig.420 P.2478 [M þ Na]þ (calcd 893. we presume that the structure of the isolated natural product needs further confirmation (See Supporting information). Successful deacetylation of the phenyl rings of compounds 11e 13 would afford the final compounds helonioside A 1.30 . The success of removal of the acetyl protecting group from the feruloyl moiety selectively is due to the fact that the ferulic ester bond is stronger than an acetate ester bond. respectively (Scheme 1).40 . Fig.6e101.29]. 12H. reaction between compound 16 and p-acetoxyferuloyl chloride 5 (1.60 -tri-Oferuloylsucrose 2 and the analog 14.2475 for C42H46O20Na).6. In comparison to the NMR spectra of compounds 8e10. deacetylation of compound 9 gave the conformationally restricted PSE 15 in 71% yield as white solid (Scheme 1). Furthermore.60 -tri-O-feruloylsucrose 2 suggested the molecular formula C42H46O20 based on the molecular ion peak at m/z 893. Hatfield et al. [26] deacetylation conditions. 30 . 2 (CH3)2C) and in the 13C NMR spectra at d 19.50 ppm compared to the same for compounds 8e10 at d 6. allowing the differentiation between the two acyl groups [27]. H-1100 for the COCH3) and acetyl ester carbon signals at d 20. The HR-MS of the 30 .40 . The crude products were purified by recrystallization from EtOAc or column chromatography (CH2Cl2/EtOAc) to afford compounds 11e13. compounds 8e10 were subjected separately to acetal deprotection using 60% aq. tri. d 20. 9H. when compounds 11e13 were subjected separately to the Hatfield et al. 2.60 -tri-O-feruloylsucrose 2 (Figs. CD3OD). . gave the expected tetra-acylated derivative 10 in 44% yield along with the tri-acylated product 9 (35% yield). / European Journal of Medicinal Chemistry 58 (2012) 418e430 p-acetoxyferuloyl chloride 5 and di-O-isopropylidene sucrose 4 (Scheme 1).5 ppm (C-1000 for COCH3).3078 [M þ Na]þ (calcd 973. the methyl5-O-acetylferuloyl-a-L-arabinofuranoside.1984 [M þ Na]þ (calcd 717.32 ppm (s. Panda et al.2001 for C32H38O17Na). Furthermore. Consequently.8 ppm (2 (CH3)2C). The IR spectrum of compound 15 further indicated the successful deprotection where peaks corresponding to the acetyl ester carbonyl group of compound 9 at 1766 cm1 have disappeared.60 -tri-O-feruloylsucrose 2 and 3.8 ppm (C-1000 for COCH3). This compound was intentionally synthesized to investigate the effect of free phenolic hydroxyl groups and the presence of additional feruloyl substituents on the antiprofilative activities.3101 for C48H54O20Na). as white solids in good yields ranging from 67% to 89% (Scheme 1).7 ppm (C1100 for COCH3) and at d 168.34 ppm (s. 1H NMR spectrum of helonioside A 1 (300 MHz.40 . 3 and 4) did not completely match with literature data especially in the sucrose unit [15]. AcOH [24]. 3H. 1764 cm1 for compounds 11e13 were missing in the spectra of compounds 1. 2 and 14 indicated the loss of the characteristic signals for the acetyl moieties on the phenyl ring.7 and 168.60 -diO-acetoxycinnamoyl sucrose 16 [24] and envisioned it to be an ideal starting substrate for the planned synthesis of lapathoside C 3 considering that the primary hydroxyl group (6-OH) of compound 16 is more reactive than the rest of the hydroxyl groups [28. the IR peaks corresponding to the acetyl ester carbonyl group at ca.0e29. 168.

respectively. Various analogs can be prepared in a similar fashion. 22 and 24 in 75%. 21. Likewise.5 ppm (C-1000 for COCH3). Compound 18 would be used to prepare lapathoside C 3 at a later stage.27] (1.1 ppm (C-1100 for COCH3) and d 168. as white solids.P. 1765e1768 cm1 observed in the starting compounds 18e20 and 23. the deacetylation was performed using pyrrolidine [27] (Scheme 2) which successfully gave compounds 3. CD3OD).23e2.6e21. Based on the spectroscopic data and also by comparison to the reported literature data for the isolated natural lapathoside C [16] (See Supporting information).30 ppm (s. 3. Thus.2283 [M þ Na]þ (calcd 833.3 equiv) afforded compound 20 in just 12% yield (Scheme 2). / European Journal of Medicinal Chemistry 58 (2012) 418e430 421 Fig. Unfortunately. d 20. 71% and 35% yield.e. 3H. reaction between compound 18 and p-acetoxycinnamoyl chloride 17 gave compound 23 as white solid in 27% yield (Scheme 2). the structure of compound 3 was assigned to be lapathoside C 3 (i. CD3OD). 22 and 24 indicated the absence of the characteristic signals for the acetyl moieties at d 2. the Hatfield deacetylation method [26] did not work on compounds 18e20 and 23 since the starting materials were recovered unchanged. 1H NMR spectrum of 30 .60 -di-Ocoumaroylsucrose). Panda et al.60 -tri-O-feruloylsucrose 2 (300 MHz. 1H NMR spectrum of lapathoside C 3 (300 MHz. Fig. 6-mono-O-feruloyl-30 . The IR spectra of these compounds were devoid of peaks corresponding to the acetyl ester carbonyl groups at ca. The 1H and 13C NMR spectra of compounds 3. 21.2263 for C40H42O18Na). Therefore. . The HR-MS of compound 3 showed m/z 833. H1100 for the COCH3). reaction between sucrose 16 and p-acetoxycinnamoyl chloride 17 [24. 4. 47%.40 .8e 169.

Table 2). Replacing one of the coumaroyl substituents at C3 of 24 with a feruloyl group as in 21 improved the IC50 value from 3.22 mM) (entries 9 & 6. of acid chloride 5 Time (d) Product Yield (%) Total yield (%) 1 1.01.62 mM) > 10 (IC50 ¼ 3. 1. introduction of more feruloyl groups seems to have positive effect on the activity. Rigid compounds having di-O-isopropylidene groups with their phenolic OH protected with an acetyl group 8. Table 3). compared to their flexible deprotected OH counterparts 1. a tri-O-feruloyl sucrose. 0. Preparation of lapathoside C 3 and its analogs. Table 2). this compound did not show any antiproliferative activity up to 100 mM concentration (entry 3.2. Table 2).60 -tri-O-feruloylsucrose 2.40 . respectively (entries 5 & 6. after cleavage of the acetyl and di-O-isopropylidene groups of compound 9 to give compound 2. Instead. / European Journal of Medicinal Chemistry 58 (2012) 418e430 Scheme 2. Increased lipophilicity of molecules was reported to be responsible for enhanced cytotoxicity [30]. Compound 21 (entry 5. Helonioside A 1 (Table 2.3 2 4 4. the positional effect of the feruloyl group on the sucrose core seems to have a great effect. The trend of the antiproliferative activity of 30 .70 mM) > 15 (IC50 ¼ 4. Additionally.70.16 mM) > 12 (IC50 ¼ 1. entry 1) and its analog compound 11 in which the phenolic groups are acetylated (Table 2. The presence of free feruloyl derivatives is: 14 (IC50 ¼ 1.67 mM (entry 7 vs 5.and chemoselective acylation of di-O-isopropylidene sucrose 4 with p-acetoxyferuloyl chloride 5. 30 . From the above results. Acetylation of 3 to give compound 18 did not improve the IC50 value (entry 1 vs 2. 5 vs 2 and 6 vs 9.67 mM. Antiproliferative activities The antiproliferative activities of natural PSEs helonioside A 1. It was anticipated that compound 6 with a mono phenylpropanoid group would show weak activity. 9 and 10 showed significant antiproliferative activities with their IC50 values of 6. entry 7) did not show any appreciable antiproliferative activity upto 100 mM concentration.12 to 1. Therefore. lapathoside C 3 as well as selected analogs 6. In this case. Table 3).1 3 2. Panda et al. Table 3) showed superior activity compared to its acetylated product 19 (entry 3.22 mM. The IC50 values of these compounds along with the standard drug camptothecin (CPT) are shown in Tables 1 and 2. Table 3). 2 and 14 (entries 4 vs 1.2 5 3 3. 15. Table 2). tetra-feruloyl PSE 14 and “mixed” PSEs 21 having a combination of coumaroyl and feruloyl units exhibited almost similar antiproliferative activity with their IC50 values of 1. Table 3).4 4 31 11 12 3 30 44 26 35 44 54 2 6 7 8 6 8 8 9 9 10 33 70 79 3.422 P.62 mM (entry 9. acetylation of the phenolic groups seems to be ineffective in enhancing the antiprolifrative activity. it is clear that the completely acetylated di-O-isopropylidene variants like compound 9 have superior activity while deacetonide (di-Oisopropylidene-free) 12 or deacetylated product 15 showed lower activities. showed improved antiprolifrative activity with an IC50 value of 22. Table 2). 2. Compound 2. the activity of the obtained product was dramatically reduced due to probable differences in the lipophilicity of these compounds (entries 2 & 5. Table 2). Entry Equiv. Tetra-phenylpropanoid sucrose esters analogs 18e22 and 24 (entries 3e7.40 . respectively.35 mM (entry 2. 18e22 and 24 were evaluated against HeLa cells using our previously reported method [24].20 mM) > 2 (IC50 ¼ 22. Table 3 and entry 9. Hence. 8e12. Table 3) showed better antiproliferative activities compared to the tri-phenylpropanoid sucrose esters analogs 3 and 18 (entries 1 and 2. 14. We suspect that substituents at the C60 position play no major role in the antiproliferative activity. Table 2) whereas tetra-O-feruloyl sucrose 14 exhibited greater antiprolifrative activity with an IC50 value of 1.16 and Table 1 Regio.35 mM). .60 -tri-O-feruloylsucrose analogs are: 9 (IC50 ¼ 0. The tetra-coumaroyl PSE 22.62 and 1.

141. H-600 ). brine (25 mL) and then dried over anhyd.51 (m.64 (d. (CH3)2C).25 g) yield.50 (m.1. respectively. 1766.6-di-O-isopropylidene sucrose 4.1. 1H. Experimental 4. Additionally.16 g) and 12% (0. H-30 . found: 663.2259. 858. H-500 . 2941.2 (C-100 ). MgSO4.4 (C-4). 2H. for the first time. 1417. The solution was then cooled to 0  C in an ice bath.2.40 a IC50 (mM): the concentration that induces 50% growth inhibition compared with untreated control cells and were calculated from three independent experiments. 111. General procedure. 2. the reaction between di-O-isopropylidene 4 (1. H-800 ).4 (C-400 ). 1H. Conclusions We successfully synthesized. 79.12 CPT 0.9 Hz.2 (2 (CH3)2C).0 (C-30 ).0 (C-1). 63. 1372. synthesized according to the reported procedures [24]. The EtOAc solution was evaporated under reduced pressure to give yellow syrup that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc as eluent to afford compounds 6e10. 2. 4.20 CPT 0. The IC50 values of compounds 2. Acylation of di-O-isopropylidene 4 with p-acetoxyferuloyl chloride 5 4.12 (EtOAc/CH2Cl2 3:2).and chemoselective acylation of di-O-isopropylidene sucrose 4.P. 55.01 9 0. FT-IR (KBr) nmax: 3452. 151. 1013. 123. 79. CDCl3) d (ppm): 19. 3H. 1511.8 (C-5). 1127. In summary. 2H.7 g. 167.22 [M þ Na]þ.57 22.01 mM compared with CPT (IC50 ¼ 0.22 11 >100 12 1.00e7. H-50 ). 943.10 :4.40 mM). J ¼ 1.1. Analytical data for 7: Table 4 IC50 values of selected synthesized PSEs 2. 3H.10 :4. 77.9 (C-800 ). H-10 a). The resulting reaction mixture was poured into vigorously stirred icewater (100 mL) and the precipitated white solid was obtained by vacuum filtration. 1712. eOCH3).8 (C-1000 ). H-5.1.5 (C300 ).3 (C-6).1.67 22 1.1. until the reaction was completed (TLC analysis (EtOAc/hexanes 3:1)).61 18 >100 19 3. H-60 b).1 0 :4.51 (2 s. skin cancer etc in search for new lead anticancer drug candidates. 1260.6-di-O-isopropylidene sucrose 7. 718. 3. 168.8 Hz. 30 . 66.t. 6 0 -mono-O-acetoxyferuloyl-2.14 20 1. 102. 1157. we can conclude that: (1) di-O-isopropylidene group proved to be essential for enhancing the cytotoxicity while acetyl and methoxy groups had much lower effects.6 mmol) in dry pyridine (10 mL) for 3 days afforded compound 6 as a white solid (0. The combined organic layers were then successively washed with 5% NaHCO3 (50 mL). 8 and 14 were selected for evaluation of the cytotoxicity at two different time intervals of drug exposure by MTS assay (Table 4) in order to examine time-dependent cytotoxicity.35 6 >100 8 6.19 (br d. H40 . 7.9 (C-60 ). 29.62 15 4. 6.3. J ¼ 15. 1H NMR (300 MHz.92 7. 1636. 103. 13C NMR (75. and (4) The PSEs examined also revealed timedependent antiproliferative activities.3 (C-3). Entry 1 2 3 4 5 6 7 8 9 10 15 Cpd IC50a 1 >100 2 22.48 MHz.1. 1199.85 (s.0 (C-900 ).40 . 24. Chemistry 2.2268. Our present results provide great motivation for the synthesis of other natural and unnatural PSEs and explore their applications and mechanism of action against various human cancer cell lines such as colon cancer. 3. 133.5 (C-40 ).9 Hz. 2993. H-6b). 7.40 . 4. 121. / European Journal of Medicinal Chemistry 58 (2012) 418e430 423 Table 2 In vitro cytotoxicity (IC50 (mM)) of selected feruloyl PSEs against HeLa cells at 48 h of exposure. H-10 b. 3. (3) Lipophilicity of the examined PSEs seems to influence the cytotoxicity in MTS model [30].0 g. compounds 2. 12H.1. H6a). 8 and 14 along with CPT at 24 h and 48 h of exposure. These compounds revealed time-dependent antiproliferative activities. H-4).62 0. 3.07 27. Analytical data for 6: Rf ¼ 0. p-Acetoxyferuloyl chloride 5 was then added slowly at the same temperature and the reaction was left to stir while warming to r. 1H.73 (m. 4. 1H.16 to 6. The MTS results revealed that 11 out of the 17 examined PSEs displayed significant antiproliferative activity against HeLa cells at 48 h drug exposure with their IC50values ranging from 0.2. H-1). trans-p-feruloyl units: 20. 3H.2.19 (m.01 1. 4.70 24 3. 1H. H-2.7 (C-20 ). 2H.47 g. 65. No Compound 1 2 3 4 2 8 14 CPT IC50 (mM) 24 h 48 h 55.90 1.45. H-1100 ). lung carcinoma. HR-MS: m/z [M þ Na]þ calcd for C30H40O15Na: 663. 3H.60 (m. 91.6-di-O-isopropylidene sucrose 6 and 30 -mono-O-acetoxyferuloyl-2. H-60 a). 1.7 (C-700 ).35 6. 1H. 30 . 73.4 (C-500 ). J ¼ 15. Entry 1 2 3 4 5 6 7 8 Cpd IC50a 3 12.23 (m. 69. H200 .60 -tri-O-feruloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSEs analogs using regio. 1601.41 (d. trans-p-feruloyl units: 2.3 (C-200 ). LC-MS (ESI): m/z 663. 1069. The results also indicated time-dependent antiproliferative activities. 73. H-700 ). (2) Substituents at the C60 position are not essential for antiproliferative activity.2 (C-600 ). 25.7 (C-50 ). the natural PSEs helonioside A 1. 3. p-Acetoxyferuloyl chloride 5 was synthesized according to the reported literature [26] (see Supporting information).7 (C-1100 ).86 21 1. 4. the position and nature of phenylpropanoid unit had a little effect on the antiproliferative activity of PSEs.40 a IC50 (mM): the concentration that induces 50% growth inhibition compared with untreated control cells and were calculated from three independent experiments.9 (eOCH3).t.1 (4 (CH3)2C). Panda et al. 3.60 -di-O-acetoxycinnamoyl sucrose 16 and p-acetoxycinnamoyl chloride 17 were Table 3 In vitro cytotoxicity (IC50 (mM)) of selected lapathoside C and its analogs PSEs against HeLa cells at 48 h of exposure.1.32 (1s.16 10 3. Lipophilicity which is influenced by the presence/absence of di-O-isopropylidene group and the number of the phenylpropanoid units on the sucrose core directly influence the antiproliferative activities. 4. The reactivities of the free OH groups of di-O-isopropylidene sucrose 4 towards acylation using p-acetoxyferuloyl chloride 5 were found to be in the order of 60 -OH > 30 -OH > 40 -OH > 3-OH. H-3). 62.4 mmol) and p-acetoxyferuloyl chloride 5 (0.5 (C-10 ). 117.70 14 1. 651 cm1. breast cancer. 31% yield) along with compounds 7 and 8 in 11% (0.30 (m. 144. 1H. Di-O-isopropylidene 4 was dissolved in dry pyridine under a nitrogen atmosphere. 8 and 14 were enhanced as the time of exposure increased from 24 h to 48 h. The precipitates were redissolved in EtOAc (25 mL) and washed once with 1 N HCl (50 mL). CDCl3) d (ppm): 1. mp: 147e 150  C.05 (m.9 (C-2). Following the general procedure. Stirring was continued at r. Herein. 4. 100.93 (m. 6. The synthetic methodology used is wide in scope and applicable to wide range of PSEs.

6. 151. 72. 25.4 (C-500 ). 133. 4.70 (m.6 (C-300 ). H-40 ). R2: 20.6 (C-1100 ).6-di-O-isopropylidene sucrose 10. 7.3 (C-100 ).70 (m.4 (C-300 ). J ¼ 12. 23.0. 1417. eOCH3). 63.62 (m. H-500 . 1766. 858. 3H. 1.4 (C-4). 2.03 (m. 151.0 (C-30 ).61 (d. H-800 ). 121.3 (C-3). Following the general procedure.34 (s. eOCH3). R2: 20. 91. eOCH3). 142. 2H. 168. 4.15 and 7. 56. 5. eOCH3). 3H. 1198.7 (C-900 ). 1H.5 (C-400 ). 141.68 (m.2 (C-900 ). 3.8 (C-1000 ).1 0 :4. 1467. H-600 ). 111. 6.1. 1327. 7. H-60 a).0 (C-300 ). 7. 70.35 [M þ Na]þ. 116. J ¼ 7.57 (d.7 (C-1100 ).9 (eOCH3).9 Hz. 123.05 (1s. H-700 ). trans-pferuloyl units: R1: 20. 77. 7. 81.7 (C-30 ).3 (C-50 ). 1067.3 (C-10 ). trans-p-feruloyl units: 2.63 (m.3 Hz. 55. J ¼ 15. HR-MS: m/z [M þ Na]þ calcd for C66H70O27Na: 1317. 3. 28.9 (C-4). 1069.1 (C-6).2839.4 (C400 ). 44% yield) along with compound 9 in 35% (0.9 Hz. 3H.9 (eOCH3). 4.2 (C-200 ). H-4.7 (C-1100 ). CDCl3) d (ppm): 1. 1332. 168. 856. 1601. eOCH3). 151. 1590.20e7.42 (m.34 g.4 Hz. 1H.1. 1H. 5. 3H.7.28e7. 3. 1. 6. 1199. 1371. 1H. R4: 20.8 (C-800 ).48 (d.7 (C-1000 ). 3 0 . 111. 1637. 25. 1H. H-600 ). the reaction between di-O-isopropylidene 4 (1. R3: 20.3. H-700 ).5 (2 (CH3)2C).48 (C-20 ). H-800 ). 3.2 (C-3). H-200 . H-10 a. J ¼ 15.7 (C-1100 ). 151.7 (C-900 ). 121. H-1100 ). 66. 1H. 3H. 77. 84.34 (s. 1H NMR (300 MHz. H-700 ). trans-p-feruloyl units: R1: 20.33 (2 m.30. 168. 1. (CH3)2C).63 (m. H-700 ). 7.7 (C-1100 ). 64. Following the general procedure. 3H. 1601 1510. H-800 ).2 (C-600 ).28e7. H-6b).3 (C-700 ).3 (C-100 ). 1H. H-10 a.52 (d. 3.02e7.8 (2 (CH3)2C). 168. 165. H-600 ).1. 70. 132. CDCl3) d (ppm): 19.6-di-O-isopropylidene sucrose 8. J ¼ 15. J ¼ 15.33 (2 m.3 (C-400 ). 90.93 (s.92 (s. 29.1. H60 a). H-800 ). 7.22 (m.84 (m. 1010. 144. 168. AcOH was heated at 80  C until the reaction was completed.7 Hz.6 (C-700 ).8 Hz. the reaction between di-O-isopropylidene 4 (1.9 Hz. H700 ). J ¼ 5.64 (m.03 (d.6 (C-1100 ). 1069. 1H. 1H. 1418. 151. 1H NMR (300 MHz.05 g) yield. 1H NMR (300 MHz. 1H.4 (C-200 ).6 Hz. eOCH3).0 g.4 (C-100 ).28e7. 4. LC-MS (ESI): m/z 1317. 3. eOCH3).3 (C-900 ). 1H. 2H. 26% yield) along with compound 8 in 44% (0. 1H.28e7.4 (C-400 ). R3: 2. 2H. 104. 2993.9 (eOCH3).3 (C-100 ). 80. 2H.9 Hz. found: 881.6 (C-1000 ). H-1). 61.3 (C-200 ). H-2. H4). 77. 73.9 g) yield.8 (C-300 ). H-500 .0 (C-900 ).92 (d. 1198. 91. 146. Following the general procedure. 947.1.4 (C-300 ). 63. 944.53 (4 s.8 (C-1000 ).1 Hz. 1467.79 (m. 111. mp: 109e110  C.10 :4.7 (C-1). 1. 91.0 (eOCH3).44. H-10 a). R3: 20. H-3. J ¼ 15. H-6a).02e7. H-800 ). J ¼ 15. 1419. H-60 a.3997.34 (s. 3H. 151. 3. 71.7 (C-700 ). 141. J ¼ 15.3401. 62. 3H. 121. 4. trans-p-feruloyl units: R1: 20. 1H.02e7. 121.87 (m.35 [M þ Na]þ. 132.7 (C-1100 ). 1H. H-3.03e7. 1H.2 (C-600 ). 1H. 4. 13C NMR (75.8 (C-5). 3. 4.9 (C-800 ).3 (C-500 ).2 (C-6). 10. 76.08 (d.8 (C-2). 3H. 80. 1H NMR (300 MHz. J ¼ 15.6 (C-30 ).3 g. 3H.02e7. 141.22 (d. 2H. H-5).4 (C-40 ). 111. 7. 1H. 1032. 56. 99.45. 123. 1033. 1511. 123. 1125. 144.3 Hz. 1333. 146.2255. 726. H-200 . 24. 2H. 3.1.3.4 (C-600 ). H-500 . 2. H-200 . J ¼ 15. 4. H-10 a. H-800 ). 166.3 (C-5). 117.9 Hz.77 (d. 133. 1716. 2942. 62.4 (C-600 ). H-1100 ). 6.9 Hz. 5. 80. H-700 ).9 Hz.7 (C-900 ). 1198.8 (2 (CH3)2C). 7. H-600 ). 3. 7.22 (m. LC-MS (ESI): m/z 663. FT-IR (KBr) nmax: 2994. J ¼ 3. 101.3 (C-100 ). 141. 7.1 (C-700 ).7 (C-500 ).92 (s.4 mmol) and p-acetoxyferuloyl chloride 5 (2.4 (C-600 ). 63.53 (m. FT-IR (KBr) nmax: 3629. 2H. H-6b. H-6b). Acetal deprotection of the diacetonoides 8e10 4. 56. H-6b). 3.38 (m.33 (s.6 (C-700 ). 796. HR-MS: m/z [M þ Na]þ calcd for C54H60O23Na: 1099. 6. 55. 3. 145. H-600 ). 66. H-10 b). H-4). 2H.50 (d. trans-p-feruloyl units: R1: 2.21 (EtOAc/CH2Cl2 3:2). 3. 168. 141.74 (m. 3H.53 (3 s.7 (C-2). H-6a). 1H. 122. 141. 1259. 133. 167. J ¼ 15. 24. 7.9 (C-300 ).1. H-30 ). 3. 133.42 (d. H-5). H-1). 65.20e 7. 4.9 (C-100 ). H-200 ). 29.9. CDCl3) d (ppm): 19. 3H. found: 663. 1601. 151.0 g. 7. 2993. R2: 20.0 (C-3).5 (C-10 ). H-1100 ). 832.88 (s.46 (m. 1H. FT-IR (KBr) nmax: 3507. 1H.3 (C-40 ). 122. 1H. CDCl3) d (ppm): 19.38 (d. 116. 166.1.9 Hz. 1372. 7. 117.3418.8 (C-900 ).5. 6.87 (s. R2: 2.8 (C-700 ).0 Hz.40.424 P. H-40 ). 7. 123.1637. CDCl3) d (ppm): 19. 151. 72. 3. J ¼ 15. 166.4 (C-400 ).9 Hz.61 (EtOAc/CH2Cl2 3:2). 13C NMR (75.6 Hz. H-3. 144.10 (m.09 (d. 3H.3 (C-200 ).1 (4 (CH3)2C). H-700 ).88 (EtOAc/CH2Cl2 3:2).4 (C-400 ).8 (C-60 ). 1H.1 (C-500 ). J ¼ 15. 111. J ¼ 15. 1. 7.02e 7. 13C NMR (75.7 (C-1000 ).91 (s. 1H. H-60 b).13 (d.33 (s.22 (m.9 (C-5).15 and 7.41.0 (eOCH3). Panda et al. 3H.86 (s. 6. 144.48 MHz.1 (C-6). 1H. 167.3 Hz. trans-p-feruloyl units: 20. mp: 130e132  C. 3.2 mmol) in dry pyridine (10 mL) for 5 days gave compound 8 as a white solid (0. 1767. 1371. 2. 650 cm1. 4. 3H. 102.1 (C-500 ). 55.8 (C-300 ). 1H. H-4). Analytical data for 8: Rf ¼ 0.19 (d.1.77 (d. H-6a).9. 6.8 (C-800 ).4 (C-300 ).33 (s.4 (C-200 ). H-1100 ).25 (d. 111.48 MHz. 3H. H-50 .76 (m. HR-MS: m/z [M þ Na]þ calcd for C42H50O19Na: 881.0 (C-60 ). 165.89 (s.3 Hz. 1H.8 (C-4). 25. 1H.3 Hz. H-30 ). 655 cm1.40.66 (d.9 Hz.9 Hz.51.5 (C-400 ).03e 7. 1H. eOCH3).0 g. 144. (CH3)2C). 855. J ¼ 15. 6. 7. 99. J ¼ 3. 4. 4.0 (eOCH3).69 (d.4. H-1).9 (C-2). 1721. A solution of di-O-isopropylidene feruloyl derivatives 8e10 in 60% aq. J ¼ 3. 3H. R2: 2.7 (C-900 ).79 (d. 3H. H-600 ). J ¼ 5. 1011. 1H. R4: 2.1.9 (C-100 ).0 (C-50 ). 123. H-500 .02e7. 7. 3. H-500 .0 (4 (CH3)2C). H-500 .93 (d. H-500 ). found: 1317. 3.94 (m. R3: 2. 116. 1H. H-500 . 73.6 (C-900 ). 1H. H-10 b).87 (m. 122. 1766. 1716. 1H.5 (C-400 ).6 Hz.2 (C-200 ). H-200 .2.8 (C-1000 ). H-50 ). 116. H-800 ). 1H.6-di-O-isopropylidene sucrose 9. 168. (CH3)2C).51 (m. 146.33 (2 m.4 (C-700 ).42 (d. 29. 1033. R2: 2. LC-MS (ESI): m/z 1099. 121. 4. 5. H-200 ).6 0 -tri-O-acetoxyferuloyl-2.86 (s.4. 132. 1H.60 (br dd. 3H.7 g. 3. J ¼ 15. 62. 727. 3 0 . 7.9 (C-300 ).8 (4 (CH3)2C). 4.89 g) yield.1.2 (C-10 ). 25. 1070. 7. H-10 b. 1.9 (C-5). 1015. trans-p-feruloyl units: R1: 2. 2H.8 (C-2).65 (m. FT-IR (KBr) nmax: 3486. H-800 ). 3H. 1H.4 0 . 944.4 mmol) and p-acetoxyferuloyl chloride 5 (1. 1012. General procedure.20 (2 m. 116.33 (s. H-60 b). 105.9 Hz.20. 70. HR-MS: m/z [M þ Na]þ calcd for C30H40O15Na: 663.12. 168. 2993.20 (2 m. 13C NMR (75.6 0 -di-O-acetoxyferuloyl-2.0. 1.08 (d.0 (eOCH3).9 (C-800 ). 3H.35 [M þ Na]þ.40 (d.33.2 (C-200 ). 2H.73 (EtOAc/CH2Cl2 3:2).53 (3 s.9 Hz.4 mmol) in dry pyridine (10 mL) for 4 days afforded compound 10 as a white solid (1. 837. 1. 4. 3. 6. (CH3)2C). 132. 61.3 (C-200 ).4 (C-40 ). 4H.15 (d. 1H. H-1100 ).0 (C-500 ). 168. 1. CDCl3) d (ppm): 1. H-60 b).0 (eOCH3). H-1100 ). H-5.2 (C-800 ). H-700 ). 906. The reaction was monitored by TLC . H-1100 ). 4. 2H.3 (C-600 ).9 Hz. 3H. 2H.9 Hz. 2936.3 (C-400 ).6 (C-1100 ).58 (m. 56. 1123. 121. mp: 135e138  C.0 (C-6). H-50 .67 g.10 :4.0 (C-20 ).2 (C-200 ).68 (d. 6. 1156. H-3. 1H. H-6a. 2H. 71. 3.0 (C-1). 2942.4 (C-50 ).40 . 123.9 (C-800 ). 1032. 141. 111.9 Hz.9 (C-1).3 (C-30 ).38 (d. 3H.6 (C-300 ).5 (C-500 ). 1765.4. trans-feruloyl units: R1: 2. 3. mp: 133e135  C. 5.5.15 and 7.3 (C-900 ). J ¼ 12. H-700 ). J ¼ 6. 903.33 (s. H-2). / European Journal of Medicinal Chemistry 58 (2012) 418e430 Rf ¼ 0.52e4. H-2).9 (C-60 ). 3. 151.61 (m.6 (C-1100 ).43 (d. 65. 99. 4. 3H. 1H. 1H. H-50 . found: 1099.77 (m. 7.13 (m. H-600 ). H-30 ).96 (m.48 MHz. 121.4 (C-400 ). 3. H-60 a). 904. H-1100 ).1 (eOCH3).43 (d. H-200 .2 (C-500 ).6 (C-700 ).2860.0 (2 (CH3)2C).5 (C-40 ). H-1100 ). 1153.15 and 7. 70. 104.2 (C-600 ).4 (C-700 ). Analytical data for 10: Rf ¼ 0.2259.66 (d. 103.0 (4 (CH3)2C). 166. H40 ).7 (C-60 ).9 (C-100 ). 1H.9 (eOCH3).8 (C-100 ). 1373. J ¼ 12. J ¼ 15. 7.1. 650 cm1.5 (C-4). 1638. 7. 56.1 (C-50 ). 64.9 Hz. 65. 168. 4. 1467.9.6 (C-1100 ). H-600 ). 1H. H-200 . 1259. 7. 99. H-700 ). Analytical data for 9: Rf ¼ 0. J ¼ 15. 1259. H-800 ).3980. 12H.13 (m. 123. 3H. 3.1. 1638. H-500 .7 (C-1000 ).8 Hz. 2H. CDCl3) d (ppm): 1.33 (2 m. 3. 101. 7. eOCH3). 12H. LC-MS (ESI): m/z 881.4 (C-1).12. 1H. 117. 66. 3. 2H. H-600 ). H-2). J ¼ 15. 7.41.4 (C-600 ).8 (C-1000 ).4 (C-700 ).4 (C-500 ).4 (C-200 ). 3H. H-1). 165.49 (4 s. 81.16e7. 1H. CDCl3) d (ppm): 1.0 (C-600 ).9 (C-800 ). 1332. 3H. 1.8 (C-1000 ). 649 cm1. 6. 12H.66 (d. J ¼ 3. 1H. 3. H-5). 56.2. 123. J ¼ 7.5 (C-500 ). H-200 . H-10 b). J ¼ 15.0 g. 30% yield) along with compound 6 in 3% (0. the reaction between di-O-isopropylidene 4 (1.5 (C-800 ).8 (C-20 ). 1721. 1H. 1H. H-600 ).21 (d.8 (C-1000 ). 55. 1260. 1H. 6.5 (C-20 ).24 [M þ Na]þ. 146.9 Hz.88 (m.9 (C-3).9 (C-100 ).4 mmol) and p-acetoxyferuloyl chloride 5 (2. 946. 2942. H-500 . H-30 ).5 (C-800 ). 101. 1H. 7. 111.6 g. 12H.33 (s.1. 123. H-1100 ). 858. 133. 71. 6. 5. H-40 ). H-800 ). 77. 72. 112. 151.88 (s. 73.3 (C-600 ).8 (C-800 ). eOCH3). 24. 116.30 .9 Hz. 118.48 MHz.8 mmol) in dry pyridine (10 mL) for 2 days furnished compound 9 as a white solid (0. 1155. J ¼ 15.9 (C-10 ). 141. 3H. 165. 111. H-60 b). H-500 . 123.07 (m.6. 141. 1124. J ¼ 8.60 -tetra-O-acetoxyferuloyl-2. 1510. 132. 1421.9 Hz.

2941. H-600 ). 118.61 (m. 1159. H-4). 1H.30 (s.60 -di-O-acetoxyferuloylsucrose 11.22 (dd. J ¼ 15.6 Hz.9 (C-1100 ). LC-MS (ESI): m/z 1237. 1638.2 (C-1). eOCH3).69 (m. 167.8 Hz. 6.8 (C-50 ).4. 3H. J ¼ 8.4 (C-30 ). 168. 123. 1H.2 Hz. 151.2. H50 ).00e7.90 g.4 (C-500 ). H-50 ). H-800 ). 93. 133. 1H.3 Hz. 9. 147. CD3OD) d (ppm): 3. 141.10 (m.6 (C-10 ).2 (C-2).2 (C-200 ). 0.0 (C-700 ).2. The products 11e13 were obtained from recrystallization in EtOAc and/or by column chromatography using a gradient of CH2Cl2/EtOAc as eluent. H-1100 ).4 (C-800 ). eOCH3). 1H. 3H.2 Hz. trans-p-feruloyl units: R1: 2.7 mmol) was reacted with 60% aq. 146. 6. 1123. 2H. 30 . 3H. H-1100 ).63 (d.5 (C-40 ).61 (d. 1. H-10 a. 1H.7 (C-900 ). 3H.35 (d. H-700 ). trans-p-feruloyl units: d ¼ R1: 20. 1032.4 (C-700 ). H-50 ). 1H.00e7. 6. 5. 7.72 (d.1 Hz.69 (d. H-800 ). 7.6 Hz. 4. 152.2792. 7.3 (C-200 ). 3H. 78. 143.4 mmol) with 60% aq. H-6a).0 (C-200 ). 9. 64. H-200 .4 (C-1000 ).53e4. H1). H-1100 ).83 (s. 124.9 (C-400 ). 1124. 168. 1H. H-200 ).31 (s. 1H. whereupon the solution turned yellow. 1H NMR (300 MHz. H700 ).53 (d. 1601. 1H.5 (C-30 ). 7.1. 6.2 Hz. J ¼ 1.27 (s. 6. H-200 .3 (C-40 ). trans-p-feruloyl units: R1: 2. 118. 121. H-3). J ¼ 2.2. 841. H-1100 ). 848.1 g. 3H.5 Hz.45 g. 168.3 (C-800 ). 3H.0 (C-400 ).1 (C-2). FT-IR (KBr) nmax: 3411.5 (C-6). 3. 1H.8 (C-200 ). 7.29 (s.01 (m. 1H. 1060. H-1100 ).40 g.5 (C-1100 ). FT-IR (KBr) nmax: 3482. 7.48 MHz. 145. mp: 128e130  C. Following the 4. 1330. H-600 ). 1012.82e5. 1H. 3H.2 (C-10 ). 3H.3 mmol) was treated with 60% aq.28 [M þ Na]þ. 7.6 (C-500 ).2 (C-200 ).9 Hz.4 Hz. 1261. J ¼ 15. 2.74 (s.4 Hz. 1H. 1467. J ¼ 5. H-1100 ). 5. 2963. 1762.76 (d.61 (dd.7 (C-1100 ). 30 .3 Hz. H-60 b. 3. H-60 a.3. H-30 ). H-5).09 (m. 73.6 g. Analytical data for 11: Rf ¼ 0.5 (C-200 ). 143.4 (C-10 ). 1720.4 Hz. 1H. 74. 166. H-3).25 (m. 153.8 (C-1000 ). 13C NMR (75. trans-p-feruloyl units: R1: 20. 1300. 170. H-6b). 3. 1H.8 (C-100 ). 1371. J ¼ 8. H-30 ). 4. 121. 151. The mixture was quenched with AcOH and was evaporated to a syrup.70 (m. H-2. 7. General procedure. eOCH3). H-4).71 (app t. 121. 1519. 1637.64 (d.5 (C-20 ).20e7. 3. 1510. eOCH3). 7. H-6a).44 (dd. H-500 .9 (C-400 ).9 (C-50 ).4 (C-500 ).32 (s. 132.2 (C-700 ).1 (C-20 ).0 (C-40 . 650 cm1. 122.40e3. Recrystallization of the crude product in EtOAc gave compound 11 as a white solid (0.45 (d. mp: 154e 156  C.9 Hz. H-5). LC-MS (ESI): m/z 1019.13 (dd. H-500 ).5 (C-1100 ).19 (d. 7. 1510. 3.88 (m. 117. 4. 141.87 (m. H-200 ). Analytical data for 13: Rf ¼ 0. H-60 a).48 MHz. J ¼ 15. 1030.6 (C-800 ).0 mL. 118. 6. 1H. H-700 ). 2H.7 (C-1100 ).3 (C-600 ).61 (m. 1218. H-6b. 1199. 836.7 (C-800 ). J ¼ 3. H-10 a).7 Hz.56 (d.6 (eOCH3). 1H NMR (300 MHz. H-1). 1H. 92. 6.8 Hz. 2H. 1220. R2: 2. 170.1. 4.4 (C-400 ). 1764.83 (s. J ¼ 3. Column chromatographic purification using a gradient of CH2Cl2/EtOAc as eluent afforded compound 12 as a white solid (0. H-6b. 113. 113. H-500 . 1632. 167. 2938.00e7. 14 and 15 as a white solid. Deacetylation of compounds 9. 151. a solution of compound 8 (1.6 (C-5). 1H.6 (C-900 ). J ¼ 1. 112. 2H.67 (m. R3: 2. After dissolving the starting material completely. J ¼ 9.5 Hz. 5. 124. 1151.82 (s.9 Hz. AcOH (66 mL) at 80  C for 20 min. H500 ). a suspension of compound 11 (0.25 [M þ Na]þ.0 (C-3). R2: 20.2 (C-600 ). Following the general procedure.93e7. 1057. 105.50 g.5 (C-1100 ). 71. 1H. 1371.86 (s. H-800 ).1.60 -tri-O-acetoxyferuloylsucrose general procedure.49 (EtOAc/MeOH 9:1).4 (C-1000 ). H-700 ). CD3OD) d (ppm): 3.1 Hz.40 . 69. 12.9 Hz. 2H. HR-MS: m/z [M þ Na]þ calcd for C48H52O23Na: 1019. 4. mp: 128e 130  C. 1H.3.2 (C-300 ). J ¼ 15.7 (C-900 ). trans-p-feruloyl units: R1: 2. 71. 1H. 143.9 (eOCH3). 134.85 (s.09 (m. H-700 ).2 (C-700 ). J ¼ 7.84 (s. 691. Analytical data for 12: Rf ¼ 0.84 (m. 788. 166. found: 801. H-6a).49 (EtOAc/MeOH 9:1). 6.07 (d.47 (d. 1325. J ¼ 3. R4: 2.00e7.1 (C-300 ).7 (C-1100 ). 792. 73. 903. 170.22 (dd. 3. 64.20e7.5 (eOCH3). 3. e OCH3). 7.78 (s. 56.2 (C-700 ).39 (d.7 (C-100 ). 116. 2H. H-4). 75. 81.5 (C-1000 ).94 (m.3 (C-600 ). 1713.5 (C-500 ). 73. 1454. HR-MS: m/z [M þ Na]þ calcd for C60H62O27Na: 1237. found: 1237.0 (eOCH3). 1H. H-40 ).9 Hz.8 g.3. 112. 797. 4. 1H. 3. H-600 ).7 (C-200 ).93e7. 3. 6.5 (C-900 ).57 (d.5 (C-5). 5. 945. R2: 20. 3.99e4. 3.4 (C-200 ). 1H. H-800 ).2. 1 H NMR (300 MHz. 425 147. 1420. found: 1019.87 (EtOAc/MeOH 9:1).3 g.3 (C-400 ).1. 143. 152. 56.1. To a separate suspension of acetoxyferuloyl compounds 9.8 Hz. 111.2. 118.30 .20e7. 2H. 13C NMR (75. 11. 146.6 (C-300 ).50 (m. H-600 ). 1H NMR (300 MHz. H-800 ). 2H.52 (m. 55.39 (m.12 (m. HR-MS: m/z [M þ Na]þ calcd for C36H42O19Na: 801. 146.26 (s. 7. 1418. H-3). 3.6 (C-700 ). 122.5 (C-800 ). 7.86 (s. R2: 2.7 (C-1000 ). 70. The solvent was evaporated under diminished pressure to furnish deacetylated products 1.2 Hz. 822. R4: 20. 56. H-500 . H-40 ).4 (C-1000 ). The reaction solution was then evaporated to dryness under reduced pressure by codistillation with toluene (3  100 mL).9 (C-500 ). 1H. 1H. 7. 3.1. 4. e OCH3).2235.48 MHz. 168. 7. H-1100 ).9 Hz. Analytical data for 1: Rf ¼ 0. H-700 ). 1465. The reaction was monitored by TLC analysis (EtOAc/MeOH 9:1). 111. 1H.10.6 (C-1). 122.61e4.9 (C-800 ).4 (C900 ).5 (C-4). CDCl3) d (ppm): 3.2774. 1H. 1H. H-600 ).4 Hz. 141. J ¼ 13. 1371. 79. AcOH (49 mL) at 80  C for 20 min. 3. 66. H-600 ). 1H. 1H. 1194.5 (C-60 ). 1). 4. treatment of a solution of compound 10 (0.9 mmol) in 95% EtOH (47 mL) was treated with piperidine (335. 122. 7.80 (m. 65.3 (C-600 ). H-700 ). H-500 .23 [M þ Na]þ.7 (C-300 ).6 Hz. 1H. 7.5 (C-500 ). 55.6 Hz. mp: 127e129  C. J ¼ 15. H-500 . J ¼ 15.9 Hz. 55. 7.9 Hz. 2H. 13C NMR (75. 4.40 . 134. J ¼ 4. 4. 1260.9 (C-1100 ). 1031. 134.3371. 3H.0 (C-100 ). 78. 30 . 5. 832. 64. 696 cm1.19 (d. H-10 b). J ¼ 15. 1H. H-2). 123.4 mmol) for 3 h to afford compound 1 as a white solid (0. 151. H-600 ).58 (d. 3H. 3. CD3OD) d (ppm): 3.8 (C-20 ). J ¼ 7. 105. H-600 ).5 (C-400 ). 124. J ¼ 15. 1H. 79. 141. 11e13 in 95% EtOH. J ¼ 8. 167. H-500 .6 (C-4). 170. 3. H-200 ). trans-p-feruloyl units: R1: 20.1 (C-30 ). CD3OD) d (ppm): 62. 124.9 (eOCH3). 3H. 6. 76. 93. 117.9 Hz.2213.49 (d.0 (C-100 ). 1H. J ¼ 15. 89% yield). H-5). H-3). H-800 ). 3H.56 (EtOAc/MeOH 9:1).60 -tetra-O-acetoxyferuloylsucrose 13. H-500 ).1 (C-400 ).78 (d. H-2).47e4. 2H. 11e13 4. 170. 4. 105. 3. 3H.46e3.65 (m.1 (C300 ). 6.16e 4. 1H. 2938.25 (m. J ¼ 7. R2: 2. 121. 3. H-1100 ). a solution of compound 9 (0. 5. H-800 ).9 (C-400 ).6 (C-2). H-200 ).1. 1H.6 (C-5).2 (C-900 ). 123. piperidine was added.4 Hz. 56. 1420. It was subjected to silica gel column chromatography using a gradient of CH2Cl2/EtOAc/MeOH as eluent. J ¼ 16. 4.2 Hz. H-30 . C-3). 1H. 3H. 995.4 (C-800 ). H-10 b.0 (C-300 ).9 (C-100 ). 134.9 Hz. 7. 3.7 (C-1100 ). H-60 b). 3. 0. 2930.7 (C-1000 ).07 (d. 8.42 (d. Panda et al. 3H.3373. 168.9 Hz. 1601. CD3OD) d (ppm): 62. 77. 165.3 (C-600 ).93e7. 6.67 (dd.68 (d. J ¼ 15. 165. H-40 ).4 (C-200 ).2 (C-600 ).8 (C-300 ). 7.59 (d. 1031. 1H. 1H. H-200 .3 (C-50 ).5 (C-60 ). H60 b). 56.8 Hz. 145.0 (C-3).9 (eOCH3). 133. J ¼ 15. 1008.P. J ¼ 9.4 (C-100 ).0 (C-900 ). 1H. 74. H-1100 ). 1H. 146. J ¼ 15. 1H. 1508. 122. 1706.3 (C-600 ).22 (m.09 (m. 6. J ¼ 16. 65. AcOH (32 mL) at 80  C for 35 min followed by column chromatographic purification using a gradient of CH2Cl2/ EtOAc as eluent yielded compound 13 as a white solid (0. 3. H-10 a.84 (d. 87% yield). 1431.60 -di-O-feruloylsucrose (helonioside A.27 (s.57 (d. 3H.7 g.39 (d. FT-IR (KBr) nmax: 3417. 1H.46 (m. 1H.26 (s. 1260.2 (C-4). H-200 ).5 (C-1). R2: 20. 996. 3H. J ¼ 15. H-10 b. 168. J ¼ 8.51 (m. R3: 2. . 649 cm1. 1H.4 (C-1000 ). 8.3 (C-600 ).8 (C-60 ). 1125. Following the general procedure. 938. 1154.0 (C-700 ). 7.35 (d. 4. 124.53 (d. H-800 ). 1H.0 Hz. 650 cm1.7 (C-900 ). 118.6 Hz. 77.6 (eOCH3). 116. H-700 ).73 (m. J ¼ 13. 1691.9 (C-300 ). 77. 3. 1273.3 (C-600 ). J ¼ 16. 1635. 7. 1H.56 (m.47 (app t. 134.9 Hz. the reaction was allowed to continue until the disappearance of the starting material. H-700 ). H-1). 7. FT-IR (KBr) nmax: 3425.5 (C-1000 ).25 (2 m.26 (s. 68% yield). 3H. 3H.24 (br s. 56. 2H. 2H. eOCH3). 5.8 Hz. 123.10 (m.82 (m. 132. 2H.0 (C-700 ).1 (C-300 ). 7. H-800 ). 1H.6 (eOCH3). H-200 ). 1601.4 (C-800 ). 938. R3: 20. H-2. e OCH3). 147. 1H. 3. 904. H-60 a). J ¼ 15. H-10 a.08 (m. 4. 1H. H-600 ). 112. J ¼ 16.4 Hz.8 (C-900 ). 3H.3. H-10 b).4 (C-500 ). 75. 1717.4 (C-400 ). 704.7 (C-6). R3: 20. 112. 0. 1155. 0. LC-MS (ESI): m/z 801. 1765.62 (m. 1H. 1H.09 (m. 1379. Following the general procedure. 7. 152. 67% yield). 1332. H-200 ).8 (C-100 ).9 Hz.6 (C-700 ).9 Hz.1 (C-800 ).59 (d.34 (br s. 5.3 (C-6). CDCl3) d (ppm): 62.8 (C-100 ). 3H.6 (eOCH3).5 (C-500 ).5 (C-100 ). 3. 1H. 143. 111. 1H.6 (C-500 ). H-4). / European Journal of Medicinal Chemistry 58 (2012) 418e430 (EtOAc/CH2Cl2 3:2). eOCH3). 153. 7.

6. 1H.4 (C-900 ). 74.0 mL. 0. 1.10 :4.30 .4.52 (m. Spectral data of helonioside A 1 was the same as reported for the isolated natural product [2.62 (m. 168. trans-p-feruloyl units: R1: 3. 2969. 3H.5 (C-700 ). 1H.9 (C-5). J ¼ 15. 846.3.9 (C-800 ). 603 cm1. 77.4 (C-600 ).4 g. 168. H-800 ).03e4. 1H. 7.4 (C-800 ). 73.9 (C-700 ).6 (C-100 ). 4.6 Hz. 6.94 (m.29 (d. J ¼ 8. 1H. 7. 111. 13 C NMR (75. J ¼ 1. H-50 ). H-5).87 (m. 1H. 168. 150. 1065. 8. 1715. pAcetoxyferuloyl chloride 5 (0.83 (s. C-3).74 (m. H-700 ).7 (C-400 ). 6.48 MHz. 124.08 (m. LC-MS (ESI): m/z 973. 1H. 6.3 Hz. 111. H10 b. H-800 ).3 (C-600 ).7 (C60 ).9 (eOCH3). 1H. 1631. 6. 1H.82 (d. H-40 ). J ¼ 15.9 Hz. 126.1 Hz. 1H. Preparation of 6-mono-O-acetoxyferuloyl-30 .0 (C-500 ). 7.1.23 [M þ Na]þ. 1H NMR (300 MHz. 8. H-500 ). J ¼ 15. 1H.60 -di-O-acetoxycinnamoyl sucrose 16 (1. 1H. 150. J ¼ 3. 2H. J ¼ 15. 6.4 (C-500 ).6 (C-800 ). Analytical data for 14: Rf ¼ 0. H-5).71 (d. H-30 ).5 (C-700 ).90 (s. a suspension of compound 9 (0. 2H. H-200 . 7. H-200 ). 1H. H-200 ). J ¼ 1.9 Hz. J ¼ 3.8. 6.6 -tri-O-feruloyl sucrose 2. 1H.2 (C-30 ). R2: 3. 4. 146. 1H. H-800 ).24 (d. Stirring was continued until the reaction was completed as indicated by TLC analysis (EtOAc/hexanes 3:1). J ¼ 15.6 (C-500 ). 147.9 Hz.2 (C-4). 24. H-4).6 (C-400 ).9 (4 (CH3)2C). 1H. 150.45 (app t. 0. 5. 6.46 (d.6 (eOCH3). R2: 56.7 (C-200 ). 145. H-60 b. 1158. H-700 ).71 (d.60 -tetra-O-feruloyl sucrose 14. J ¼ 7. H-800 ).5 Hz. 1457.6 (C-1).08 (m. 1H.48 MHz.1 Hz. 1H.7 (C-100 ). 65. 79.81 (d. mp: 145e147  C. 147. 70.2 g. CD3OD) d (ppm): 62. 6. 1H. 150.3 (C-700 ). H-10 b. H-600 ). 150.7 (C-1). J ¼ 15. 71. H-600 ). 93. 1699. 1708. 101.7 (C-100 ). J ¼ 15.1 (C-800 ). 69.9 (C-900 ). FT-IR (KBr) nmax: 3423. LC-MS (ESI): m/z 717. 6. J ¼ 15.57 (m. H-200 . 819. H-60 b).9 Hz.1 (C-900 ).72 (s.6 (C-400 ). FT-IR (KBr) nmax: 3067. 5H. found: 893. H-600 ). H-600 ). 1H. J ¼ 8.08 (m. H-6a).4 (C-400 ). eOCH3). H-500 . 1383. H-600 ). H-800 ). 148. trans-p-feruloyl units: R1: 3.4 (C-300 ). J ¼ 15. H-500 . 1H.t. H-40 ). 4. H-700 ). 7. 845.4 (C-4).9 (C-400 ). 124.1 Hz.59 (br s.4 (C-100 ). 148.5 (eOCH3). eOCH3).34 (d.45 (dd. 1H. 1H. HR-MS: m/z [M þ Na]þ calcd for C48H54O20Na: 973.65e3.72 (d. H-500 ).8 (C-20 ). 655. H-6a).17 (br s.8 (C-100 ).31. 30 .3 (C-600 ). 3.9 (C-500 ).6-di-O-acetoxyferuloyl-30 .1 (C-3. H600 ). 6. 146. 1H.9 (C-300 ). 114. R3: 56. H-200 ). H-500 .90 (s. 5. 64. 3H.50 (d.1. H-6b.2 Hz. 1H. mp: 123e125  C. 73. 1. J ¼ 15. H-60 b. 105.2 (C-900 ). 4.44 (d.7 (C-400 ). 1H. 2H.2 (C-2). 149.75 (m.8 (C-500 ). 1. H-3).8 (C-4).4 (C-600 ).3 (C-4).6 (C-800 ). found: 1069.1 (C-900 ). 124.2475. HR-MS: m/z [M þ Na]þ calcd for C42H46O20Na: 893. 168. H-600 ). 4.8 (C-200 ). 1H.7 (C-900 ). C-40 ). trans-p-feruloyl units: R1: 56. 1372. 63. H-800 ).4 Hz.2926. 2. The precipitate was redissolved in EtOAc (25 mL) and . trans-p-feruloyl units: R1: 55.08 (m. 112.4 (C-600 ). 1H. 93. 30 .3 (C-700 ). 147. 7.95e7. 1465.37 (d. eOCH3). 126.2 (C-600 ). 1H.5 (C-100 ). 12H.1.7 (C-60 ). H-30 . 169.5 Hz. 2H. 149. 3.47 (m.2 (C-300 ). 1272. 3H. R2: 56. 116. 1H.83e7. 1H NMR (300 MHz.41 (d. 168. 115. H-60 a). 76% yield). 116. H-500 ).6 (C-100 ).07 (m.58e4. 6. a suspension of compound 13 (0. 1003.46e4. (CH3)2C). R4: 3.2 mmol) in 95% EtOH (16 mL) was reacted with piperidine (150. Panda et al. 2H. 3.4 (C-700 ). CD3OD) d (ppm): 3. R3: 3. 1271. 1H.3 (C-10 ).8 Hz. 3H. 105. 1.9 (C-100 ). 168. J ¼ 15. J ¼ 15.2 g.1. R3: 56. 6. H-2.50 (m. H-1). J ¼ 15. 0. 1157. C-40 ). 1H.16 (m.48 MHz.8 (C-10 ).37.4 (C-5). 2940. 166.82 (d. eOCH3).20 g.3 (C-600 ).2 (C-3). 1H. 3H.9 Hz. R2: 3.1 Hz. H-700 ). 2H. 124. 4. H-40 ). LC-MS (ESI): m/z 1069. 7. 1H. 113. 124. 0. 1. 166.0 (C-6).1. H-6a). 149. 127.4 Hz. found: 973.80 (m. 1H. 127.8 mmol) for 4 h to give compound 15 as a white solid (0. 2H.4 (C-1). 14.5 (C-100 ).41 (d. H-600 ).0 (C-3).8 (C-300 ).6-di-O-isopropylidene sucrose 15.8 (C-300 ).7 (C-400 ). 816. 6.1 (C-200 ). J ¼ 15. 6. 99. H-60 a). 7. 1595.1 (C-200 ).7 Hz. 0.4 g. 116. H-500 ). 6.8 Hz. 815 cm1. H-10 a). CD3OD) d (ppm): 62. 6. Following the general procedure. 6.05 (m. 4. J ¼ 8.15 g. H-500 ). J ¼ 3.26 (d. 3. R3: 56. 1H. R4: 56. mp: 99e101  C. 66. 7.08 (m.0 (C-600 ). 7. 6. 64. eOCH3). 113.5 Hz.3 mmol) in 95% EtOH (23 mL) was treated with piperidine (176. 1H.59 (d. 111.9 (C-500 ).54 (d. 113. / European Journal of Medicinal Chemistry 58 (2012) 418e430 3. 64.4.76 (s. 1H NMR (300 MHz. 148. 5. 115. H-60 a). 111. 1H. 79.10 (dd.9 (C-800 ).1 Hz.9 Hz.6 (C-200 ). 7. H-2). H-3).5. Synthesis of lapathoside C and its analogous 4. 149.2 (C-900 ). 1H. H-800 ).7 (C-200 ). eOCH3). H-50 .4 (C-200 ).8 (C-900 ).4 (eOCH3). 5. Analytical data for 2: Rf ¼ 0. H-200 .9 Hz. 2H. 78. 114. 3H. 1H. H-700 ). 4. H-40 ).3 (C-300 ).76 (d. 6.5 (eOCH3). 109.0 mL.5 (C-500 ).3078. 7. H-4. 5. H-700 ).9 Hz.8 Hz. 167.27 [M þ Na]þ.21 [M þ Na]þ.9 Hz.1 g.45 (d. 4. 146. 1H. 3. 1H. 856.0 (C-40 . 127. Analytical data for 15: Rf ¼ 0.80 (dd.2 mL. 1H. 1H.81 (s. 2939.7 (C-400 ). 149.7 (C-400 ). R2: 3. trans-p-feruloyl units: R1: 3. 4. J ¼ 7. H-1).3 g.4 mmol) in 95% EtOH (28 mL) was treated with piperidine (232. 3H. 2H.14 (dd. H-700 ). H-60 a). 1594.5 (C-100 ). J ¼ 15.0 (C-800 ).95e7. 150.27 (EtOAc/ hexanes 3:1). 7.5 (eOCH3). 147. R3: 3.1 g.88 (m. 5.7 (C-400 ). 71% yield). J ¼ 15.9 Hz. Following the general procedure.40 .29 (m. 3H. 4. R2: 56.9 Hz.7 (C-20 ). J ¼ 8. H-800 ).60 -tri-O-feruloyl-2.95e7.5 (C-200 ).60 -di-O-acetoxycinnamoylsucrose 18 and 3. 1H.1 (C-30 . 149. H-500 ). 0.2 (C-300 ). H-500 ).9 (C-50 ). 114. 3H. 5. 66. HR-MS: m/z [M þ Na]þ calcd for C52H54O23Na: 1069. 6.74 (d.5 (C-400 ). 127. trans-p-feruloyl units: R1: 56. H-1). 6.4 (C-300 ).40 . CDCl3) d (ppm): 1. 1653.4 (C-800 ). 74.8 (2 (CH3)2C).426 P.1.2 g.62 (m. Following the general procedure. 148.3 (C-30 ). 116. 1H. 1430. H-200 ). H-200 . H-800 ). 111. a suspension of compound 12 (0. 91. 1593. H-5).4 (C-300 ). 75. 112. 1154.3 (C-900 ). H-4.57 (m.81 (m.87 (s.60 (d. H-800 ). 4.1 Hz. 4.16 (m.8 (eOCH3). trans-p-feruloyl units: R1: 56.4 (C-700 ). 127.0 mL.3 mmol) for 4 h to afford compound 2 [15] as a white solid (0. 74. 2H. 65. 724. 6. 1271. J ¼ 1. H-600 ).48 MHz. 942. 109. 123. J ¼ 9. 150. 1516.6]. 3H.0 (C-6).4 (C-6). 75. 6. After 24 h. 1431.29 (m.73 (m.4 (C-300 ). 114.5 (C-500 ). 73. 1211.2 (C-700 ). 4. H-6b). 7.66 (d.9 (C-100 ).8 (C-200 ). eOCH3). 1031. 1H.4 (C-200 ). H-800 ). 114. 146. H-600 ). eOCH3). H-200 . 147. 1452.2001. 1H. 1715. 1H. 28.08 (m. 1517.9 Hz.2 (C-700 ).60 -di-O-acetoxycinnamoylsucrose 19. 2H. H-50 ).2 (C-60 ). 3. 1515.0.6 (C-100 ). 4. R2: 55. 7. 127. H-2. 169. H-700 ). H-30 ). CD3OD) d (ppm): 3. 703. 1H.9 (C-60 ). 147.6 Hz. 116. 1H.9 Hz. 116. 4. 7.9 (C-800 ).8 (C-20 ).96 (m. 3H. 127. 6.2 (C-900 ).1 (C-1). 1.5 (C-600 ).9 Hz. J ¼ 5.8 (C-800 ).74 (m. J ¼ 1. H1).94 (m. H-200 . 65.49 (m. J ¼ 4.74 (m. 78. R3: 3.59 (d. 124.9 (C-50 ).57 (d. 2H. 1H.16 (m. J ¼ 15.79 (d. 7. trans-p-feruloyl units: R1: 3.77 (s.3 (C-600 ).4.83e7.9 (C-800 ). 2991.9 Hz. 148. 115.4 mmol) were added.25 [M þ Na]þ.6 (C-5). H-30 . J ¼ 15. 1034. H-6a).6 (C-200 ). C-30 . J ¼ 8.6 Hz. 13C NMR (75.4 . J ¼ 15. 5. 104. 105.2 (C-10 ).5 (C-500 ). 7.46 (EtOAc/MeOH 9:1).4 Hz. 114.5 (C-500 ).35 (br d.22 g.54 (d.9 Hz.14 (m. H-6b).1 Hz. 4. 1H.51 (d.3. H-200 .1 (C-20 ). 1H.5 mmol) for 4 h to afford compound 14 as a white solid (0.5 (eOCH3).28 (br d. 1H. CD3OD) d (ppm): 62.4 (C-600 ).2 (C-700 ). 109.92 (s.1. 11. H-10 a. 3H. 65% yield). LC-MS (ESI): m/z 893.1 g.2478. 2H.18e4. 6.86 (m. 1. 1H.8 (C-900 ). 1H.73 (EtOAc/MeOH 9:1). e OCH3). 25. 77. 1H.0 (C-400 ).9 Hz.83e7. 5. 603 cm1. H-700 ).3 Hz. 3.2 (C-300 ). 149. 1H.42 (d. eOCH3). 1H. H-700 ). 150.23 (m.8 (C-2). 81. 13C NMR (75.3. H-700 ).2 (C-2). 146.8 (C-200 ). FT-IR (KBr) nmax: 3355. 1. 116. 149. 124. CDCl3) d (ppm): 19. H-600 ). H-3. 2H. 93.58 (d. 6.1984. 3H. found: 717. 6.8 (C-50 ). 112. 124. H-6b). 7. eOCH3). H-500 ). 116. J ¼ 15.8 (C-5).5.8 (C-700 ). 3H.4 (C-300 ).7 (C-6). H-10 a. 2964. H-50 ).7 (C-2). 3. J ¼ 15. 114.49 (3 s.70 (d.5 (C-700 ). 1H. the resulting mixture was poured into vigorously stirred icewater (100 mL) and the white solid precipitated was obtained by filtration. 13 C NMR (75.5 (C-500 ). 6. J ¼ 1. 62. H-800 ). 127. H-60 b.3 (C-50 ). 2H. 77. 124. 114. 1032. 150.5 (eOCH3). H-500 ).87 (s. 3. H-5). H-600 ). 123.1 (C-40 ). H-700 ). The solution was then cooled to 0  C in an ice bath.0 (C-800 ).5 mmol) was dissolved in dry CH2Cl2 (21 mL) to which 4 Å molecular sieves powder and dry pyridine (1.4 (e OCH3).1. HR-MS: m/z [M þ Na]þ calcd for C32H38O17Na: 717.08 (br d.9 Hz.3 (C-900 ). 7. 992. 114. 6. 1H. J ¼ 8.24 (d. 166.3.1 (C-600 ). 111. 127. 126.64 (m. 77.95 (m.5 (C-500 ). 1431.5 Hz. H-10 b).9 Hz. 3 . 1H. 71.2948. R2: 3. 0 0 0 4.9 Hz. 149. 3H.6 mmol) was then added slowly at the same temperature and the reaction was left to stir while warming to r. 1H. 147.3101.0 (eOCH3).20 (d. 3H. 124. J ¼ 15. 1H.84 (s. 1632. 72.02 (m.90 (m. e OCH3). 77.9 Hz. 116.59 (d. 7. J ¼ 8.9 Hz. H-200 .88 (s.4 (eOCH3).5 (C-10 ).

146.48 (m. 7.00e7.9 Hz. 2H. 145.3 (C-10 ). LC-MS (ESI): m/z 1177. 6. H-500 ). H-300 . trans-p-coumaroyl units: R2: 21.53e7. H-40 ).94 (d. 1559. 5. H-2.46 (m. H-1). R2: 2. 1123.82 (m. C-600 ).47 (d. HR-MS: m/z [M þ Na]þ calcd for C40H42O18Na: 833. 2363.52 (d.4 (C-900 ). 1767. 127.5 Hz.3 (C-900 ). R3: 21. H-50 ).23 (s.24 (d. H60 b. 1457. H-600 ).6-di-O-feruloyl-30 . e OCH3). The appropriate fractions were concentrated under diminished pressure to a residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc/MeOH afforded compounds 3 and 21.1 (C-100 ). H-200 .65e3. The starting material typically dissolved within 15 min and the reaction was allowed to continue until the disappearance of the starting material as indicated by TLC analysis (EtOAc). 4.29 (d. 117.7 Hz.9 Hz. 141. 1H. H-200 .3 (C-400 ). 2956.6 (C-1100 ).42 (d.75 (d. 1H.74 (m. 4. 2340. H-800 ). 7.2 Hz. 149. 129. 2H. J ¼ 15.6-di-O-feruloyl-30 .50 (m. 2926. 167. H-700 ). 5. 1457.5 (C-600 ). J ¼ 16. H-800 ).6 (C-700 ). mp: 125e127  C. C-500 ). 1602.28 (s. H-1100 ).5 (C-500 ).82 (m. 121. 64.1 (C-300 . H-300 . eOCH3). CD3OD) d (ppm): 3. H-800 ).5 Hz. eOCH3). 131.56 (m.3 (C-400 ). mp: 135e138  C.6 (C-300 ). 75% yield). 1321. 80.4 (C-400 ). H-4). 55. H-60 a). 2H. 2852.88 (s. 5H.28 (s.4 (C-10 ).5 (C-200 .48 MHz. 117. H-200 .55 (m. 168. H6b. 3.1 (C-100 ). 1H. 7. 1H. R4: 2.60 -di-O-coumaroylsucrose 3 and 3. J ¼ 16. 6. 595 cm1.65 (m.8 (C-20 ). 1604.7 (C-1100 ). 1H. 4. J ¼ 16.82 (m.48 MHz. J ¼ 16. 1H. 1637. 6. J ¼ 16. 116. H-600 ).41 (dd.5 (C-700 ). H-800 ).30 (s.5 (C-1). MgSO4.6 (C-800 ).4 (C-800 ). 47% yield).9 (C-200 . H-40 .53e7.28 (m. 3H.5 (C-200 ). H-4). 6. J ¼ 5. 1H.8 (C-60 ). trans-p-coumaroyl units: R1: 2. found: 833. 104.54 (m. 1032.2 Hz. trans-p-feruloyl units: R3: 3.4 (C-200 ). 64. 65. 141.2 g.54e7.98e7. 152.24e 4.4 (C-40 ). 64. 1059.50 g.5 (C-1000 ). 169. 1H NMR (300 MHz. 1713. H-200 .29 (d. LC-MS (ESI): m/z 959. 7.1 (C-1100 ). 3. 1H. C-500 ).2 (C-700 ).9 Hz. 946. H-3). H-500 ).32 (m.2.6 (C-3). 1015.98e 7. 1170. 4. H-500 ). J ¼ 15. J ¼ 15. 169. 1061.26 (d.8 (C-200 .73 (d. H-700 ).3 (C-800 ). H-700 ). 3H. H-600 ). 72. 168. 1H. 1540. 111. 74. The aqueous layer was extracted with EtOAc (25 mL). 2H.7 (C-700 ). 116.5 (C-20 ).1 (C-1100 ). 133. 7. H-5). 6. 2H.67e 4.74e6.4 (C-5).34 (d. H-5.4 (C-800 ). 1031. 0. H-2). 1011. H-300 . 1H. H-700 ). H-700 ). H-1100 ). 7. 111.54 (m.7 Hz.3159.62 (d. 1508. 3423. H-800 ). 169.1. 1H. 1H. 122.64 (m. J ¼ 8. 2H. H-300 . J ¼ 15. 0.11 (m. 7. 151.52 (d. 6.2 (C-200 . 1H.0 mL.4 (C-800 ). 1H. 7.4 (C-800 ).9 Hz.1 g. 1635. 2H. J ¼ 7. 116. trans-p-coumaroyl units: R2: 114. H-6a.46 (d. 4.62 (d. a suspension of compound 19 (0. trans-p-feruloyl units: R1: 20.9 (C-900 ). 5.5 (C-800 ). 4. 2H. 1H. J ¼ 15. 123.1. 1H. 831.2283.16 (m.2.1 (C-100 ). J ¼ 1.47e7. 122.02 (d. 1455.4 Hz. 1H. Following the general procedure.74 (m. Pyrrolidine were added to a suspension of compounds 18 and 19 in 95% EtOH. H-4).1 (C-4). 2H.29 (m. 1H.5 (C-6). 70.74 (m. FT-IR (KBr) nmax: 3483. 1H. H-5). H-30 ). 4. it caused the solution to turn yellow.4 (C-200 .56 (d. 2925.9 Hz.4 (C-400 ). 1H NMR (300 MHz. 2H. H-600 ). 1H. J ¼ 8.79 (d. 4. 92. 3. H-700 ).1 (C-700 ). 909. 1H. 64. H-6a. 1700. 69. H-1100 ).54e7. H-50 ). 1710. H-30 ). 7.75e 6. 1374. 836.2 (C-900 ). 116.8 (C-800 ). H-2). 1419.0 mL.6 mmol) for 3 h to afford compound 21 as a white solid (0.81 (s. 150. 1H. 7.6 (C-100 ).0 (C-5). J ¼ 9.9 mmol) for 90 min to furnish lapathoside C 3 as a white solid (0. 147.84 (s. 121. 2H. Analytical data for 21: Rf ¼ 0. 7.9 (C-1000 ). 7.6 (C-1). 91. 74. 3. 6. 168. 1602. C-600 ).1. J ¼ 15.16 (m. 2H.74e6. H-500 ). J ¼ 15. 1. 1H. General procedure. 4.8 (C-100 ). C-600 ). 1H. trans-p-feruloyl units: R3: 20.65 (d.2 Hz.42 (br s.1 Hz. 1169.39 (d. 7. 7. 2340. 1203. H-200 . 117.30 (d. 6. 1517. 2H.2 (C-900 ). 76. 1H. 123. 166.09 (m. 1H NMR (300 MHz. 4.74e6. H-800 ). 1H NMR (300 MHz. 6. 1457. 1260. 2H. 1H.34 (dd. 6. 152.60 -di-O-coumaroylsucrose 21 4. Spectral data of lapathoside C 3 was the same as reported for the isolated natural product [16]. FT-IR (KBr) nmax: 3363. 1282.0 Hz. 13C NMR (75. 1766.9 (C-3). 1H. 1164.2 mmol) in 95% EtOH (10 mL) was treated with pyrrolidine (155. 4. 7. J ¼ 16. H-700 ).8 (C-30 ). 91.30 (s.5 (C-30 ). 2340. 1636. 3. 3H. H-1). H-700 ).41 (d.60 -di-O-coumaroylsucrose 21.3 (C-4).4 (C-400 ). 1H. 1H. 1261. H-800 ).0 (C-30 ).2 (C-300 . J ¼ 8. 147. 71. Following the general procedure. 1056.6 (C-10 ). Consequently. H-600 ). 131. H-600 ). 7.9 Hz. H-200 ).4 (C-200 . H-3).2 Hz.12 g) yield. H-1100 ).4. 111. 2H. FT-IR (KBr) nmax: 3447.9 Hz. 131.52e4.4. 124. 146. 932.01 (dd.1 g. 131.57 (br s. H-50 ). 4.9 Hz. 1H. 1H. H-50 ). 6. J ¼ 9. purified by PTLC afforded compound 18 as a white solid (0. trans-pferuloyl units: R1: 56. 1. 1H.4. 7.9 (C-900 ). H-200 ).9 (eOCH3). 1H. 3H. 79.1 (C-1100 ). 7. 2H. J ¼ 16. J ¼ 15. H-200 . 3. 1H. 1H. 168. 151.2 (C-1000 ).81 (s.9 Hz.13 [M þ Na]þ. C-500 ). trans-p-coumaroyl units: R1: 21. 1H. 1087. 36% yield) along with compound 19 in 7% (0.7 (C-100 ). 2362. H-40 ). H-200 . H-700 ). 997.2 (C-400 ).9 (C-1). 152.33 (m. 116. H-10 b.24 (m. H-800 ).3 (C-700 ). 161. 1328. 2363.24e4. 1H. 5. 7.2 Hz. J ¼ 15.46e4. 167.8 (C-1000 ). 1508. H-1100 ).11 (EtOAc/hexanes 3:1). 1337. 666 cm1. H-800 ). 427 4. R3: 114. 146. H-1. J ¼ 15. 121.65 (m. 1H.4.60 (m. 1445. 0. 3. R3: 6. 3H.54e7. R2: 21. 1206. H-60 b). 3H.62 (m. Analytical data for 19: Rf ¼ 0. 6. 168. C-600 ).65 (m.8 (C-1000 ). 2H. H-1). transp-coumaroyl units: R2: 2. trans-p-coumaroyl units: R1: 6. 4. 152. 668 cm1.16 (m. 2H.14 [M þ Na]þ.2. H-500 ). 131.3159.8 Hz. 3H. CD3OD) d (ppm): 3. C-60 ). 167. H-600 ).65 (m. 5.1 (C-1000 ). 1H. H-800 ). 1H.59 (m.1. H-500 . 122. 1266.9 (eOCH3). The EtOAc solution was concentrated to residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc as eluent and further. C-500 ).6 (C-700 ). 1H. 127. H-500 ). trans-p-feruloyl units: R1: 2. . 1371. 1H. trans-p-feruloyl units: R1: 3.28 (s.3.2. 2H. 2855.P. 3H. 4.74 (EtOAc/ MeOH 9:1). 1H. 2924. 81.0 (C-40 ). 1371.82 (m. H-300 .0 Hz. C-600 ).49 (d.9 (C-100 ). 168.8 (C-6. 1H. H-600 ). 0. H-300 . 3. H-6b.9 Hz. H-500 ).1 (C-4).5 (C-700 ).18 (m.5 (C-20 ). CDCl3): d (ppm): 3. H-200 . H-6b).48 (d. H60 b.68 (m. H-700 ). H-4).5 (C-300 ).65 (m. 3.4 (C400 ). 3.64 (m. 6. R4: 3. CD3OD) d (ppm): 65. 129. / European Journal of Medicinal Chemistry 58 (2012) 418e430 washed with 1 N HCl (2  50 mL). 1H. 129. H-600 ).09 (m. 5. 3H. 2H.2 Hz. HR-MS: m/z [M þ Na]þ calcd for C46H48O21Na: 959.47e7. brine (25 mL) and then dried over anhyd. 79. H-600 ). 834. H-3). 3). J ¼ 8.64 (m. 1H. H-60 b. 122. H-500 ).1 (C-300 . 1H. 71. 2H. 133.71 (m.8 (C-300 . 1H.2 Hz. H-60 a).75e 6. 1H. 946. 55. trans-p-feruloyl units: R3: 2. 1H. C-500 ). 2925. 5. H-500 ). 6. 73.04 g. 72. 831.3 (C-300 ). H-600 ).7 (C-6). CDCl3) d (ppm): 63.6 (C-300 ).9 (C-50 ).15e4. 9. 144. 7.06 (EtOAc/hexanes 3:1). H-5). 129.9 Hz. HR-MS: m/z [M þ Na]þ calcd for C58H58O25Na: 1177. H-200 .36 (d. 104. H-700 ). 169. 1165. 144. 55.2 Hz. found: 1177. 1H. H-60 a). 5. H-500 . 4. 1H. 6. H-6a).6 (C-50 ). 1323.3 (C-900 ). H-300 . 2852. LC-MS (ESI): m/z 833.11 [M þ Na]þ.2549. 3H. R2: 6. H-500 ). 80.3 (C-5). 80. 3H. H-700 ). 6.1 (C-100 ).9 Hz.54 (m. CDCl3) d (ppm): 64. 3H.2 Hz. C-500 ). H-1100 ).4 (C-200 ).5 (C-60 ). H-60 a).98e7.7 (C-800 ). H-10 b). 7. 167.57e5. H-10 a).2 (C-400 ).16 (m.51 (d.00e7. 6. 145. H-10 a.25 (m. mp: 114e116  C.3 (C500 ).43 (d. H-800 ).8 (C-900 ). 794.1 (C-2). 3.48 MHz.4 (C-900 ). 1H.2 Hz. 1H.21 (m. 161. This mixture was directly added to a column of strongly acidic ion-exchange resin [Amberlite IRA-120 (Hþ) washed and packed in 95% EtOH.55 (EtOAc/MeOH 9:1).53 (m. 1467. H-10 b.82 (m. 1419. J ¼ 16. 987. H-600 ).1.9 Hz. H-1100 ).8 (C-300 . J ¼ 15. 74. mp: 108e110  C. FT-IR (KBr) nmax: 3457.6 (C-100 ). H-40 .13 g. CDCl3) d (ppm): 3. 7.18 (dd. H-800 ).82 (m.7 Hz. H-6b. 73. 1698. 649. 3421. 133. 3H. 4H. 7. 169. 6.8 (C-700 ).5 (C-500 ). The combined organic layers were then successively washed with 5% NaHCO3 (2  50 mL). H-600 .32 (m. eOCH3).53 (m. 115. C-600 ). 1517.9 (eOCH3).1 (C-50 ). trans-p-coumaroyl units: R2: 6. H-3). H-2. 7. a suspension of compound 18 (0.7 (C-2). 3H.2580. 6. H-10 a). 2H.5 (C-200 ). 3H.53e7.7 (C-1100 ). 111. 117. eOCH3). 71.75e6. J ¼ 8. 145. H-800 ). 1277.4 (eOCH3). 2H.1 (C-1000 ).98e7. 1128.1 (C-700 ). 151.4 Hz. found: 959.2.40 (d. Preparation of 6-mono-O-feruloyl-30 . 2H.40 (d.9 (C-900 ).84 (s. H-500 ). H-200 . 123. Analytical data for 3: Rf ¼ 0. 141. H-300 . 912. 3. 1.1 (C-1100 ). 754. 127. 1H. 3H.00e7. Panda et al. 4.2 (C-600 ). 1636. J ¼ 7.6 (C-500 ).09 (m. H-30 ).60 -di-O-coumaroylsucrose (lapathoside C. 104.2 (C-600 ).1 mmol) in 95% EtOH (5 mL) was reacted with pyrrolidine (130. R3: 2.4 (C-800 ). 6-mono-O-feruloyl-30 .1 (C-100 ). 13 C NMR (75.2263.6 (C400 ).1 g. 652 cm1. Analytical data for 18: Rf ¼ 0. 131. 166.26 (s.21 (br s.1 (C-300 . 5.35 (m. 7.5 (C-400 ).8 (C-3). 1H. 7. H-6a). H-10 b. 4.7 (C-40 ). R4: 20. 3H. H-30 ).2 (C-600 ). 70. 75. H-700 ). 1H.77 (s.60 (m.2 Hz. 7. H-10 a. 4. 9. 13C NMR (75. 7. 6. J ¼ 16. H-200 . 116.55 (m.6 (C-2).

0 (C-1). J ¼ 9.4. 6. 6.05 (d.3 (C-400 ). 1058.30 . 162. The solution was cooled to 0  C in an ice bath and p-acetoxycinnamoyl chloride (17.2 g. H-700 ). 649 cm1. 2H. J ¼ 15.6 (C-2). 3. 105.1 (C-300 .t.29 (d. J ¼ 15. The combined organic layers were then successively washed with 5% NaHCO3 (2  50 mL) and brine (25 mL) and then dried over anhyd.8 (C-200 ).5 (C-60 ). 7.6 (C-6). J ¼ 15. trans-p-coumaroyl units: R1: 2. The solvent was concentrated to residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc as eluent followed by PTLC furnished compound 23 as a white solid (0. 144. 124. 5. H-700 ). 169. 15. H-700 ). 147. 1704. 117. Preparation of 6-mono-O-acetoxyferuloyl-3.4. LC-MS (ESI): m/z 1117. 1H.1 (C-900 ). Analytical data for 20: Rf ¼ 0. 1H. MgSO4. 7. 1207.27 (dd. 7.9 Hz.1. 169. 2H. H-1100 ). 1H.38e7. Preparation of 3.3 g. C-600 ). 149. H-200 . 131. 1H.27 (s. 72.1. 129. 0.1.8 (C-700 ).6 (C-50 ).51 (d. 3H. H-800 ). H-1). 92. CDCl3) d (ppm): 63.4 (C-300 ). The appropriate fractions were concentrated under diminished pressure to a residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc/MeOH to furnish compound 22 as a white solid (0. 2H.48 MHz. H-6a. H-800 ). 3.9 (C-100 ). 1540.81 (m. H-200 .4 (C-30 ). trans-p-coumaroyl units: R1: 6.6 (C-800 ). 5. C-600 ). 7. H-50 . HR-MS: m/z [M þ Na]þ calcd for C48H46O19Na: 949. 76. CDCl3) d (ppm): 3. 116. 1H. 1457. The starting material typically dissolved within 15 min and the reaction was allowed to continue for 15 min.6 (C-400 ).3 (C-100 ). 13C NMR (75. CD3OD) d (ppm): 65.70 (m.48 (d.2 (C-400 ). 117. CD3OD) d (ppm): 3. 1060. H-800 ). 7. 836.44 (d. H-10 a.9 Hz. 71. Analytical data for 23: Rf ¼ 0. 129.8 Hz. 169. H-30 ).0 (C-4). 1H. 77. J ¼ 15.9 Hz.57 (m. 1559.8 Hz. 1169.14e4. 1H. 122. H-5. 1507.12 g.0 (C-700 ).7 (C-900 ). R2: 2. The combined organic layers were then successively washed with 5% NaHCO3 (2  50 mL) and brine (25 mL) and then dried over anhyd. H-10 b). H-60 b).61 (m. H-500 ).8 (C-800 ).9 Hz. 6. 1H.30 .9 Hz.9 (C-800 ).54e7. 132. R4: 2.2948. C-500 ).6 (C-50 ).3 (C-900 ).12 [M þ Na]þ.4 (C-200 . 4. 2340. 127. 65. J ¼ 15. H500 ).62e4. 7. 131.8 (C-800 ).54e7.1 (C-1100 ). 2. 946.46 (m.35 mmol) was added slowly at the same temperature and the reaction mixture was left to stir while warming to r. R3: 21.27 (s.8 (C-900 ).6 Hz.73e6. 169.48 (d. 7.6. 7. 124. 6.46 (m. 30 . 72. 7. 144. 1H. 1441. 162. 1718.4.40 (d.7 (C-800 ). 169.54e7. 81. 1H. J ¼ 6. H-60 b. H-600 ). 1H. FT-IR (KBr) nmax: 3428. H-30 ).43 (EtOAc/hexanes 3:1). 2H. 116. 122.4 (C-400 ).2526. 1004.44e7.3 (C-3).2737. C-500 ). 1371.38 (m. 2H.5 (eOCH3).5 (C-300 ). R3: 6.2 mL. 2957. The precipitate was redissolved in EtOAc (25 mL) and washed with 1 N HCl (2  50 mL).5 (C-400 ). 1H. J ¼ 1.76 (EtOAc/MeOH 9:1).30 (m.4 (C-100 ). R3: 2. 4. 74.78 (m.9 (C-200 . 1H. 117. 147. 7.0 mL) and pyrrolidine (70. 2H.9 Hz.0 mL.60 -tri-O-coumaroylsucrose 24 4. 0. 0. 93.1 g.9 (C-40 ). 2H.81 (m. H-700 ). R4: 21.27 (s.6 (C-700 ). Panda et al. R4: 115. 7. C-500 ). 4. 80. C-600 ). 6. 6.4 (C-5). H-500 ). mp: 113e115  C. mp: 149e 151  C. H-50 ). C-600 ).2 (C-700 ). 5.5 (C-400 ). 169. FT-IR (KBr) nmax: 3415. C-500 ).65 (m. 1700.66 (m.33 (app t.3 mmol) were added.76 (d. R2: 21.9 (C-300 . H-300 .03 g. 1H. 77. The aqueous layer was extracted with EtOAc (25 mL). 1H.9 Hz.60 -di-O-acetoxycinnamoyl sucrose 16 (1. H-300 .68 (m.05 (d. 117.4 (C-700 ).5 (C-40 ). 1559.81 (m. H-60 a). 2363. 1322. 7. Preparation of 3. 80.0 Hz. 146. found: 1009. 147. The EtOAc solution was concentrated to residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc as eluent followed by PTLC afforded compound 20 as a white solid (0.9 Hz. 0. 1H. H-6a).7 (C-400 ). 169.60 -tetra-O-coumaroylsucrose 22 4. 2H. 2H. H-200 . 4. 2H. 92.62 (d. 2922. 1635.18 (dd. 1H. 1H.7 (C-60 ). 3H.8 (C-100 ).2 (C-1000 ). H-600 ). 4. 7.6 (C-900 ). 2337.38e7. 127. 152.08 g.3 (C-800 ).66 (m.60 -tetra-O-coumaroylsucrose 22.0 (C-3). H-300 .5 (C-5). 64.2.6. H-10 a).5 (C-200 . 1636. 2H.9 Hz. H-700 ). H-60 a).53 (m.t. 864. H-700 ).4 (C-200 . 131.6. 12% yield).2 Hz. H-800 ). 13C NMR (75. H-500 ). 152.73e6. 7. H-300 . the starting material was completely disappeared as indicated by TLC (EtOAc/hexanes 3:1). 2H. H-2. 72. C-500 ).9 (C-700 ). 1369.5 (C-400 ). 70.1 (C-1100 ).1 (C-600 ). H-2). H-40 .4 mmol) was dissolved in dry CH2Cl2 (7 mL) to which 4 Å molecular sieves powder followed by dry pyridine (0. 3.3 mL.8 (C-400 ). 7.4 g. 1H.1 (C-100 ).7 (C-100 ). C-600 ). 115. 1283. 116. J ¼ 9. 4.82 (d.8 (C-5).1 g.50e4.81 (m.40 (d. 169.9 Hz.8 (C-6). R3: 115. 1H. 115.8 (C-200 ).0 (C-800 ). 1266. Compound 20 (0.76 (d. H-300 . 7.4 (C-100 ). 117. 3H.6 (C-300 . 162. 146. J ¼ 15. 152. C-600 ).3 (C-700 ).54e 7. 65. H-800 ). 1H. Synthesis of 3.4 (C-700 ). 168.4.2 (C-1000 ). 6. LC-MS (ESI): m/z 1009. H-1). 105. eOCH3). H-800 ).5 (C-800 ).7 (C-100 ).59 (m. 79. 6.43 (EtOAc/hexanes 3:1).5 (C-4). 27% yield). 1H. 129.57 (d. J ¼ 7. 4.60 -tri-Oacetoxycinnamoylsucrose 23. 1604.57 (m.34 (d. 145. H-1100 ). 1. C-600 ).4 (C-300 . 152. R4: 6. 2850. H-200 . 74.2 (C-1000 ). 7.3 Hz. H-200 . 167.4 (C-900 ).64 (m. 4H.15 [M þ Na]þ. 3H. 1602.5 (C-20 ).0 (C-700 ). R2: 115.4 (C-700 ). H-500 ). Compound 18 (0.1 (C-1100 ). trans-p-coumaroyl units: R1: 114. H-700 ). / European Journal of Medicinal Chemistry 58 (2012) 418e430 3H. H-300 .9 (C-300 . 169. 64. H-6b.66 (m. H-600 ). 7.8 (C-6).2 (C-100 ). 127. . 111. H700 ). The resulting mixture was poured into vigorously stirred ice-water (100 mL) and a white solid precipitated was obtained after decantation and filtration.6 (C-200 . 1H. C-500 ). H-6b).49 (m.2 Hz.4 (C-400 ). 111.8 Hz. 70.4 (C-20 ). 1327. H-5).5 mmol) was dissolved in dry CH2Cl2 (21 mL) to which 4 Å molecular sieves powder and dry pyridine (1. 792. 1. 1H. FT-IR (KBr) nmax: 3475. 117. H-500 ). H-500 ). 7. 2H.6 (C-600 ). 1.54e7. 6. 150. 2923.1 (C-1100 ).8 (C-4). R2: 6. Synthesis of 6-mono-O-feruloyl-3. 1H.62 (m. C-500 ). 6. H-200 ). 131. 7.05 g.2740. 167. H-1100 ).5 Hz. 169.74e6. 71% yield). 127. 2934. Stirring was continued for 24 h.3 (C-800 ). 1H NMR (300 MHz. H-700 ).1 (C-300 .4 (C-900 ). H-500 ). found: 1117. 147. 2362.73e6.9 (C-900 ). C-600 ). 122.27 (s. 169. 1009. trans-p-feruloyl units: R3: 56.5 g. R4: 56.3. H-3).2918.5 (eOCH3).8 (C-700 ).2 (C-50 ). 2H. C-500 ).0 (C-2). 1516.9 (C-10 ).6 (C-800 ).8 mmol) was added. 4. 81.7 (C-60 ). H-600 ).14 [M þ Na]þ.6 (C-500 ). H-600 ). 1H. H-4). H4). 1H. 147. found: 949.73 (m. Stirring was continued until the disappearance of the starting material as indicated by TLC (EtOAc/ hexanes 3:1). HR-MS: m/z [M þ Na]þ calcd for C56H54O23Na: 1117.1. LC-MS (ESI): m/z 949.2 (C-400 ).1.6 (C-20 ). the resulting mixture was poured into vigorously stirred ice-water (100 mL) and a white solid precipitated was obtained after decantation and filtration. 65. 7. 104. C-500 ). 3. 1765. 127.0 (C-900 ). H-3).4. 116. CD3OD) d (ppm): 65.05 (d. 79. 69. 1H.0 (C-30 ).66 (m.1 (C-800 ).5 (C-800 ). 150. H-600 ). Analytical data for 22: Rf ¼ 0. 65. 131.3.7 (C-10 ).4 (C-700 ).9 Hz.48 MHz.3 (C-900 ).19 (m. 7. 2H. The precipitate was redissolved in EtOAc (25 mL) and washed with 1 N HCl (2  50 mL). 0. 131.7 (C-200 . 7. 1H NMR (300 MHz. 9.05 mmol) was suspended in 95% EtOH (4. 4. J ¼ 3. 166. H-200 . 1H. H600 ).20 g.1 (C-200 .3. H-500 ). J ¼ 15. 1169. C-500 ). 148.1 (C-300 .4. H-600 ).2 (C-1000 ). 0.60 -tetra-O-acetoxycinnamoylsucrose 20.30 . mp: 113e115  C.38 (d. H-800 ). H-600 ). The aqueous layer was extracted with EtOAc (25 mL). C-600 ).05 (d. H-1100 ). 127. J ¼ 15. H-40 .30 .4 (C-500 ). 2340. 4. 1H. 129.07 (dd. C-600 ).49 (m. 2H.1 (C-300 . 2H.5 (C-300 . 161.30 .7 (C-40 ).44e7. 127. 116. 122. 1768. MgSO4.9 Hz.3 Hz. 161.3 (C-10 ). trans-p-coumaroyl units: R1: 114. J ¼ 16. 0. The mixture was directly added to a column of strongly acidic ion-exchange resin [Amberlite IRA-120 (Hþ) washed and packed in 95% EtOH].56 (br s.60 (m.3 (C-200 . 71. J ¼ 7. 2H.73e6. J ¼ 15.9 (C-900 ).2494. 2H. 13C NMR (75. H-300 . 162.3 (C-100 ). 131. H-300 . 5.49 (m.68 (m. 168.9 (C-200 . trans-p-coumaroyl units: R1: 21.46 (m.2 (C-30 ). 127. 831 cm1. 149. 74.48 MHz.2 (C-1). Reaction was monitored by TLC analysis (EtOAc). 7.38e7. 117.38 (d. 5.44e7. 911.7 (C-1). H-800 ).9 mmol) was added (which caused the solution to turn yellow).2 (C-900 ).4.6 (C-2). J ¼ 15. 1H.0 mmol) was added slowly at the same temperature and the reaction mixture was left to stir while warming to r. R2: 114. After this time. 1H. H-10 b). 5. 1H.4 (C-300 .1. After 24 h.9 (C-100 ). 1H. J ¼ 9.7 (C-200 .2 (C-400 ).5 (C-3).1. 2H. 131. 1419. 147. 70.8 (C-100 ).428 P. H-200 . HR-MS: m/z [M þ Na]þ calcd for C50H50O21Na: 1009. 3H.26 (m. H-200 . The solution was then cooled to 0  C in an ice bath and then p-acetoxycinnamoyl chloride 17 (0. 2362. H-800 ). 3. 131.

61 (m. H-600 . Shao.7 (C-900 ). 1054. 5 (2009) 615e620. 116. Hostettmann. 649 cm1. Biochem. H700 ).J.50e7. Appendix A. Y. and Polygonum sachalinensis F. 1540.9 (C-800 ). 80. T. 1320.8 (C-800 ). Hsu. H-500 ).9 Hz. 131.27 (m.69 (m. 117. 2H. H-700 ). L. H-30 ). C600 ). 1H. Schmidt ex Maxim (Polygonaceae). 839. 3H. 3H. Steroidal glycosides and aromatic compounds from Smilax riparia. 152. 6. G.4 (C-5). 6.57e7.9 (C-100 ).T.L. C. Ye. 4. Lee.1 (C-1000 ). Takamura.2 (C-600 ). J ¼ 15. 151.13 [M þ Na]þ. 0.78 (m. Nat.9 Hz. 5.9 (C-1). 6.4 (C-200 ).C. 116. S. 1765. 71.76 (EtOAc/MeOH 9:1). HR-MS: m/z [M þ Na]þ calcd for C49H48O20Na: 979.2 (C-800 ). 152. Chin. 111. W. 5H. 987. 129.5 (C-30 ). Larson.5 (C-400 ). 104. H800 ). 1H. J ¼ 15. Lee. H-500 ).30 .C. 1H NMR (300 MHz. Med. C-500 ). 169.9 Hz.48 MHz. Gao. 7.6 (C-10 ). M. J ¼ 6. Pharm. The mixture was added directly to a column of strongly acidic ionexchange resin [Amberlite IRA-120 (Hþ) washed and packed in 95% EtOH]. 123. Steroidal saponins from Smilax china and their anti-inflammatory activities. [10] K. X. 104.25 (m.0 (C-100 ). H-800 ).J. Jinfu. the starting material was completely disappeared as indicated by TLC analysis (EtOAc). Antiproliferative activity of selected PSEs against HeLa cells Antiproliferative activities of the selected PSEs against HeLa cell lines were evaluated using MTS assay method [24] at 24 and 48 h of drug exposure (For the details see the Supporting information). 121. 3.43 (m. Fan. H. 2H. 131. Jun.5 (C-20 ). Z. 1H. H-300 . H-700 ).1 (C-1100 ).5 (C-60 ).83e6.8 (C-900 ). K. Ono. 6. 1H. E. 7. 74. H-800 ). J ¼ 15. Antioxidant phenylpropanoid glycosides from Smilax bracteata. Nohara. 1205. H-6a). Appl.91 (m. H-2).3 (C-900 ).6 (C-400 ). Pharm. Han. 8 (2002) 170e172.29 (s. A. T.6 (C-50 ).R. 3H.67 (m. Acknowledgements This research was supported by a grant from the National Medical Research Council (NMRC).8 (C-1000 ).9 Hz. 71. 1H.89 (s. Sugita. Chem. 1H. T. L. [14] Y. 160. Prod. 1H.4 (C-800 ). 76.2 (C-600 ). 2H. H-700 ). M.0 (C-4). 79. H-30 ). H-4).57 (d.57 (br s. K.-F. Fitoterapia 81 (2010) 124e131. 5. trans-p-coumaroyl units: R1: 21. Chin. [13] H.Y. 7. Y. C-500 ). Nat. 1718. L. 167. 1H.8 (C-400 ). 6. C-600 ). 7.47 (d. Marston. Phytochemistry 69 (2008) 1398e1404. 167. [16] M.-J.C. 987 cm1.17 [M þ Na]þ. Z. Judeh. / European Journal of Medicinal Chemistry 58 (2012) 418e430 1718. H-50 ). Pharm.5 (C-800 ). 2H. [18] P.M. 1699. Huang. 61 (1998) 762e766. Feruloyl sucrose derivatives from Bistorta manshuriensis.4 (C-800 ). Syst.K. D. Ikeda. M. H-200 .7 (C-300 ). R2: 2. Wang.1 g.9 (C-200 . 4. 1H. 13C NMR (75. W. 6.ejmech. Qingyun.46 (d. [11] J. Cui.1 (C-1100 ).7 (C-10 ). 127. 74. 1H. 1054.9 Hz.J.93e7. Chem. [8] L. J ¼ 15. [9] L. Zhang. J.10. 122. yunnanensis. J ¼ 15. Yang Kuo.3 429 (C-200 ).5 (C-900 ). 2H.6 (C-300 ). found: 1147. 1009. W. 3H. 116. C-600 ). 7. H-700 ). H-200 .83e6. 1734. Wang. 5. H-600 ). 80. H-800 ).57e7. 122. H-200 .-X. H-60 a). H-40 .0 (C-100 ). 168. Huang. Zhu. H-6a. H-500 ). 7. 2H.17 (m. 6. 69. 145.40 (d. Prod. CDCl3) d (ppm): 3. H-200 .2631. trans-p-feruloyl units: R4: 20. H-200 ).60 -tri-O-coumaroylsucrose 24. Hitoshi.03 g. 1H. Fitoterapia 79 (2008) 306e307. trans-p-feruloyl units: R4: 56. 1H.2 (C-900 ). H-6b. 1320. 1559.Q. H-600 ). J ¼ 15. J ¼ 15. Kim. Appalashetti. Nohara. Park. H-40 . 2H. J. K.6 (C-100 ). 1. 1H. Y.50e7. 1H. T. Chang.4 (C-200 .67 (m. Brown.50e7. Zhongguo Zhongyao Zazhi 31 (2006) 1691e1693. 1602.3036.67 (m. J ¼ 15.7 (C-1100 ). H-1). Kuo.4 Hz.17 (m.9 Hz. Y. R3: 21. 133. Liaw. (CD3)2CO) d (ppm): 3. Yuqing.91 (d. H-600 ). Y. Zhang. Zhang. C. 127.9 Hz. eOCH3).47 (d.1 (C-800 ). Chen. 145. 1H NMR (300 MHz. Yoshimitsu. T.35 (m. K. Schmidt ex Maxim. 141.-E. Y. New phenylpropanoid esters of sucrose from Polygonum lapathifolium. 2362. C. Min.1 g. Nakano. 7. 1636.28 (s. Gao. Cytotoxic activities of Indigenous plant extracts in cultured human cancer cells. CDCl3): d ¼ R1: 63. found: 979. Hay.6 (C-500 ).93e7. C-600 ). Fan. Li. A novel phenylpropanoid glycosides and a new derivation of phenolic glycoside from Paris Polyphylla var. Lou.70 (m.Y. Chem. Chemical variability of the invasive neophytes Polygonum cuspidatum Sieb.67 (m.2012.9 (C-6). Xu. 0. H-6b. [5] M. Park. 167. 1165.4 (C-200 . 4. 167.3 (eOCH3).13 (d.29 (s. eOCH3).1 (C-200 . The starting material typically dissolved within 15 min and the reaction was allowed to continue for 3 h. 1H. 4. H-200 . Chem. Curr. 145. 55 (2007) 551e556. Kuroki.1 (C-300 . Fitoterapia. Panda et al. Ikeda. 152. H-800 ). 1H. 167. Zhang. The appropriate fractions were concentrated under diminished pressure to a residue that was subjected to column chromatography using a gradient of CH2Cl2/EtOAc/MeOH to afford compound 24 as a white solid (0. 1457. H-60 a).1 (C-100 ). [15] J. 116.6 (C-3). Marston. Bull.2 (C-400 ). 169. 127. Y.9 Hz. 34 (1986) 5005e5010. Lee. C-500 ).81 (s. [6] L. 18 (2007) 548e550. Chem. [3] T.H. Wang. Cytotoxic phenylpropanoid glycosides from the stems of Smilax china. 2H. H-3). 1260. A. 1374. T.5 (C-700 ). Murakami. H-500 ).4 (C-200 . After this time.M.62 (d. H-800 ). [4] B. 1H. H-300 . 3H. H-600 ). C-600 ).0 Hz. Wang. LC-MS (ESI): m/z 1147. 1559. 3H. 160. Y. 792.M. 1419. 6. H-600 ).49 (d.7 (C-700 ). 150. 146.0 (C-50 ). 1H. trans-p-feruloyl units: R4: 2.9 (C-700 ). H-700 ).9 Hz. R3: 115. Y. Sci. 115. 1165. 3H. H. 2337.83e6. 1281. Biol. H. H-800 ).0 mL. L.9 (eOCH3). 126. (CD3)2CO) d (ppm): 64. 65.8 (C-3). Youxing. C-600 ). 1260. T. Hwang. Hongfang. J. 5. H-10 b). 4. J.4 (C-2).1 (C-300 .57e7. 6. [7] L.org/10. Nat. 55. 1H. 1602.77 (d. H-700 ). Z.P. Hay. Kim.55 (m.J. 148. Li.4 (C-400 ). R2: 115. Environ. H-1100 ). 131.1.91 (m. 3H.2 (C-700 ). Analytical data for 24: Rf ¼ 0. Phytochemistry 53 (2000) 1051e1055.1 mmol) in 95% EtOH (7 mL) was stirred with pyrrolidine (143. Shen. 91. R2: 21. 68 (2005) 1475e1478. 4.3 (C-30 ). 1507. Q.H. H. C-500 ). 7. 64. 2H. Guo. 3. H-500 ). Yan. 3H. H-500 . yunnanensis. mp: 78e83  C. A new phenylpropanoid glycosides from Paris polyphylla var.7 (C-6).30 (m. 1009. 124. S. Two new steroid glycosides and a new sesquiterpenoid glycoside from the underground parts of Trillium kamtschaticum. A. 81. 1H. 7.1 (C-300 . Z.-J.5 (C-700 ).45 (m. Guo.8 (C-100 ). 3H. Can. H-2. 160.77 (d. Prod.36 (d. 72. H-10 a.K. 166. Vanicosides. 3H. Terrier.F. H-800 ).4 (C-40 ). 92. 6. 1H. H-1100 ). H-60 b). Takaishi. 167. 129. J ¼ 15. Chem. 122.48 MHz. Gao.30 (s. Masuoka. Y.67 (m. H60 b. These data include MOL files and InChiKeys of the most important compounds described in this article. H-600 . 1457. Preparation of 6-mono-O-feruloyl-3.7 mmol) which caused the solution to turn yellow. 117. [12] Y. 3H.67 (m.3 (C-700 ). 146.4 (C-800 ). H-200 .36 (br s.7 (C-300 . H-500 ).4 (C-1).3 (C-900 ).J. 37 (2009) 24e34. 6. 1H. H-5. [2] K. 1205. Takasaki. New phenylpropanoid glycosides from Polygonum pensylvanicum. Yang. FT-IR (KBr) nmax: 3428.0 (C-500 ). 116.8 (C-20 ). . 1H. Zheng. H-1).7 (C-400 ). 129.3054. 64. 1H.67 (m. R2: 6. 913. 7. J. Yan. J.80 (m. C. 2340. F. 131.0 (C-4). trans-p-coumaroyl units: R1: 6. 80 (2009) 143. A suspension of compound 23 (0. 54 (2006) 1451e1454. [19] L. A. 2H. Konoshima. at http://dx. Y.1 (C-1000 ).7 (C-40 ). H-300 .A. 70. Nat. 13C NMR (75. Feruloyl sucrose derivatives from Heloniopsis orientalis. 4.1 (C-400 ).41 (d.27 (m. H-50 ).9 (C-900 ). 1H. A.9 Hz. Sneden. Supplementary data Supplementary data associated with this article can be found in the online version. 4.93e7.6 (C700 ).H. Phenylpropanoid glycosides from Smilax glabra.3 (C-60 ).58 (m.4. 1281. J.37 (d. 6. E. 3. [17] P.9 (C-200 . 7. Singapore (EDG10nv043). References [1] P. 146. 144. J ¼ 8. Kuo.2612.93e7. 70. 2H. Tomimatsu. LC-MS (ESI): m/z 979. S. H-5).5 (C-100 ). J ¼ 3. H-300 . H-600 . 88 (2010) 519e523. Bull. 1419.C. Bull.T. 4. 168. Zhang.9 Hz. 18 (2011) 3234e3251. Phenylpropanoid sucrose esters: plant-derived natural products as potential leads for new therapeutics. H-3).1 (C-1100 ). 7. H10 a. C.56 (d. 034. Corrigendum to “A new phenylpropanoid glycosides from Paris polyphylla var. 117.J. H-300 . H-10 b). R3: 6. H-200 . 1540. H-300 . Prod.91 (m. Lett.4.doi. 1374. Phytochemistry 68 (2007) 623e630. H. Liao. 1H.9 (C-100 ).C. 76. 168. 131.3 (C-400 ). HR-MS: m/z [M þ Na]þ calcd for C57H56O24Na: 1147. 65. 2H. Q. H-4. H-700 ).8 (C-900 ).Y. C-500 ). J ¼ 15. Lee. Zhang.Y. trans-p-feruloyl units: R4: 3. 1636. Kozuka.1 Hz. 130. 111. Y. Fitoterapia 79 (2008) 306e307. H-1100 ). J ¼ 8. 145. trans-p-coumaroyl units: d ¼ R1: 2. Studies on chemical constituents in roots of Rumex dentatus. H. C.1 (C-700 ). H-1100 ). yunnanensis”.52 (d. J.2. Bi. S. Guo.E.R. 7.W. 6. Ecol.57e7. M. 64 (2001) 1305e1308.2. C-500 ). M. 5.8 (C-1000 ). 35% yield). Chemical constituents from Polygonum perfoliatum. R3: 2.17 (m.17 (m. 1507.6 (C-2).8 (C-300 . 5. 1H.W. H. trans-p-coumaroyl units: R1: 115.2 (C-5). 2923. H-500 ).7 (C-300 .1016/j. 1653. Hostettmann. and Zucc.83e6. Panda. Antioxidant and enzyme inhibition activities and chemical profiles of Polygonum sachalinensis F.

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