NOTE TO THE EDlTOR

Carbon-13 NMR Spectral Studies on some

Labdane Diterpenoids
Amarendra Patra* and Alok K. Mitra
Department of Chemistry, University College of Science, Calcutta 700 009, India
Swapna Biswas, Chitra Das Gupta, Ajoy Bas& and A. K. Bama
Department of Chemistry, Bose Institute, Calcutta 700 009, India

Carbon-13 NMR signal assignments of the labdane diterpenoids andrographolide and 14-
deoxyandrographolide, along with their acetates, and isodeoxyandrographolide have been made. This study
indicates that the C-6 and C-11 resonance assignments of isovirescenol-B, made earlier, should bk
interchanged.
Andrographis paniculata (family Acanthaceae), a bit-
ter shrub well known as kalmegh in West Bengal,
forms the principal ingredient in the household
medicine for general debility, dysentry and certain
forms of dyspepsia.'*2 The main bitter constituent,
RO q0
andrographolide (1) has been characterized as a
diterpene-lactone of the labdane g r ~ u p . ~Four
- ~ more
related compounds of the labdane series, namely, neo-
andrographolide, 14-deoxy-ll-oxo-andrographolide, RO"
14-deoxy-11,12-didehydroandrographolideand 14-
deoxyandrographolide (2)were also isolated6-* from 1 R=H 2 R=H
the same source. We have studied the 13C NMR 3 R=Ac 4 R=Ac
spectra of 1,2 and some of their derivatives (3-5) and
the data obtained are presented in Table 1. The COOR~
assignments of the resonances have been made on the
basis of chemical shift theory, and also by considering

the changes in chemical shifts produced by the change
of substituent(s) and comparison with the shift data for
the labdane diterpenoids 69 and 7: dimethyl
agathatel' (8) and related compounds." Due to shor-
tage of material, no further proof could be obtained
and the assignments, while self-consistent, are tenta-
tive until such time as further work can be carried out.
This is the first time that the 13C NMR studies of
labdanes bearing a lactone carbonyl at C- 16 have been
carried out and these data should be useful in elucidat-
ing the structures of new members of this group of
natural products. The aim of the paper is to present
data for future workers in the field, and the assign-
ment of the individual resonances are not discussed
where shifts are as expected.
The lactone carbonyl signal at 6 170.0 in 1 was also
present in the spectrum of 3, but appeared at a slightly
deshielded position (-3.5-4.3ppm) in 2, 4 and 5,
probably due to the absence of the y-effect of the
-OR function at C-14. The association of C-8 in 1
with the signal at 6 147.6 was substantiated from the
absence of this signal in 5. The non-protonated
olefinic carbon resonances at 6 126.9 and 137.9 in 5
were assigned to C-8 and C-9, respectively, the low
field position of C-9 being justified from the consider-
ation of substituent effects.ll
* Author to whom correspondence should be addressed.
CCC-0030-4921/81/0016-0075$01.50
:7
m
R1 R2
5
6 R' = OH, R2 = CH,,
R3=H
7 R' = OAc, R2 = CH,,
R3=H
8 R' = H, R2 = COOCH,,
R3 = CH,
The methine carbon signals at 6 64.7 in 1 and 6
67.3 in 3 were associated with C-14 since this signal
was absent in 2 and 4. The identification of C-15 and
C-19 was relatively straightforward by comparisoln
with the 13C NMR spectrum of isovirescenol-B1' (9)
and 19-hydro~y-ent-kaurene.'~ The methylene carbon
signal in the region 6 62.9-64.0 in 1-5 was assigned to
C-19 since a similar resonance (6 64.7) for C-19 was
also present in 9. Furthermore, the C-19 resonance in
1 was approximately 2.4 ppm to high field compared
to that of C-19 (6 65.3) in 19-hydro~y-ent-kaurene,~~
due to the y-effect of the additional hydroxyl function
at C-3 in 1. The methylene signal at 6 74.4 in 1 was

@ Heyden & Son Ltd, 1981 ORGANIC MAGNETIC RESONANCE, VOL. 16, NO. 1, 1981 78
 A. PATRA ET AL

Table 1. Carbon-13 chemical shifts (6) of andrographolide (l), its acetate (3), lbdeoxyandro-
grapholide (2), its acetate (4), isodeoxyandrographolide (5), the labdane diterpenoids 6,7,
8 and isovirescenol-B (9)
,S.b
Carbon 2b 3b 4b 5b 69 79 *lo 9'2

1 36.7, t 36.6, t 36.4, t 36.2, t 34.4, t 37.1 36.8 39.0 35.4

2 28.0, t 27.8, t 24.7. t 23.7, t 27.5, t 27.8 24.3 19.8 29.2
3 78.7, d 79.9, d 79.1,d 79.1, d 79.8, d 78.9 80.7 38.0 81.0
4 42.4, s 42.3, s 40.8, s 40.7, s 42.0, s 39.2" 38.1 44.2 43.0
5 54.6, d 55.0, d 54.6, d 54.6, d 51.3, d 54.7 54.8 56.1 52.1
6 24.1, t 23.7, t 23.7, t 23.7, t 18.4, t 24.0 24.0 26.1 21.6
7 37.6, t 37.9, t 37.3, t 37.6, t 33.5. t 38.2 38.1 38.5 33.1
8 147.6, s 146.6, s 146.2, s 146.0, s 126.9, s 147.7 147.5 147.4 125.1
9 55.7, d 55.8, d 55.2, d 55.2, d 137.9, s 56.0 55.9 55.2 136.7
10 38.7, s 38.7, s 38.4, s 38.5, s 38.0, s 39.5' 39.3 40.1 37.4
11 24.1, t 21.6, t 24.l.t 21.2, t 25.7, t 21.7 21.8 21.5 19.1
12 146.4,d 24.2. t 149.3, d 24.2, t 25.7, t 40.0 40.0 39.6 34.9
13 129.1,s 134.1, s 123.7, s 133.4, s 133.7, s 163.7 163.4 160.5 35.1
14 64.7, d 144.1, d 67.3, d 144.0. d 144.1, d 114.9 115.1 114.7 42.0
15 74.4, t 70.0; t 71.0,t 69.5, t 70.0, t 171.4 171.8 166.9 146.2
16 170.0, s 174.3, s 170.1, s 173.5, s 174.2, s 19.2 19.2 19.0 111.1
17 108.4,t 107.2, t 108.2,t 106.7,t 20.4, q 106.9 107.0 106.2 28.3
18 23.1, q 22.5, q 22.1, q 21.9, q 22.2, q 28.3 28.3 28.6 22.9
19 62.9, t 63.8, t 64.0, t 63.8, t 63.7, t 15.4 16.5 177.3 64.7
20 14.9, q 14.9, q 13.9, q 13.9, q 18.9, q 14.6 14.5 12.4 20.6
ccH3 20.5, q 20.4, q 21.3
II 20.5, q 20.3, q
0
20.5, q
co 169.8, s 169.9, s 171.0
169.8, s 169.5, s
168.3, s
50.9
OCH, 50.5
a In d,-DMSO; a,,, = 8dS.DMSO+39.6 ppm.
Multiplicity in the SFORD spectrum is given after the respective chemical shifts: s(singlet), d(doublet),
t(triplet) and q(quartet).
Assignments interchangeable.

thus assigned to C-15 which resonated at a somewhat
higher field in 2 and 4 due to the absence of the -OR
function at C-14.
The change of the 8:17 double bond to the 8 : 9
position in 5 caused shielding of C-1 (2.2ppm), C-5
(3.7 ppm), C-6 (5.3 ppm) and C-7 (4.4 ppm) since they
lie in the shielding zone of the 8 :9 double bond; C-20
experienced an approximately 4 ppm downfield shift.
Compound 912 has the same oxygen functions at C-3
and C-19, and the relative stereochemistry at C-3,
C-4, C-5 and C-10, as that of 5; the 13C NMR signals
for C-1-C-5, C-7-C-10 and C-18-C-20 in 9 were thus
closely comparable to those of 5. Since C-6 in 5
resonated at 6 18.4 it is evident that the C-6 and C-11
resonance assignments for 9 in Ref. 12 should be
interchanged. Furthermore, comparison of the signals
of 1 with 69 and 3 with 79indicated that the effect of
oxygenation at C-19 was pronounced only on C-4 and
C-18.
EXPERIMENTAL
The I3C NMR spectra were recorded on a Varian
Associates CFT-20 NMR spectrometer operating at
20.1 MHz in the FT mode. The compounds were
submitted to proton-noise decoupling and single fre-
quency off -resonance decoupling. The samples were
run in 5 mm 0.d. tubes using CDCl,, unless otherwise
stated, as solvent as well as internal lock. All solutions
were c. 10-15% in concentration. The solvent signal
was used as internal standard. The chemical shifts
reported are in 6 (pprn) downfield from TMS; =, ,a
8CDC,3+76.9ppm. The spectra were run with sweep
width 4000 Hz; a 6 ks pulse (approximately 45" tilt
angle) was employed with approximately 2 s delay
between pulses.
Andrographolide (1)was isolated from the leaves of
Andrographis paniculata following the method of
Chakravarti et a l l 4 1 afforded the triacetate 3 on
heating with acetic anhydride and anhydrous
ZnCl,.R,14 NaBH, reduction' of 3 gave 14-deoxy-
andrographolide diacetate (4). 14-Deoxyandro-
grapholide (2) was obtained on deacetylation of 4 by
refluxing with 0.5% aqueous methanolic KHCO, solu-
tion on a steam bath.' Iso- 14-deoxyandrographolide
(5) was prepared from 2 by acid-induced isomerization
of the exocyclic double bond to the 8 :9 position (as in
the case of neoandrographolide to the isoaglycone6)by
refluxing with 5% ethanolic hydrochloric acid for 5 h.
All compounds were purified by chromatographic re-
solution over silica gel. The identity of 1-4 was estab-
lished by comparison with their respective physical
(m.p. and [ ( Y ] ~ and
) , spectral (UV, IR and 'H NMR)
data. The structure of 5 was derived from UV, IR, 'H
NMR and mass spectral studies.

76 ORGANIC MAGNETIC RESONANCE, VOL. 16, NO. 1, 1981 @ Heyden & Son Ltd, 1981
 CARBON-13 NMR SPECTRAL STUDIES ON SOME LABDANE DITERPENOIDS
Acknowledgements
The authors are grateful to Professor (Mrs) A. Chatterjee, Depart-
ment of Chemistry, Calcutta University, and also to Professor S. C.
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Received 24 July 1980; accepted (revised) 10 December 1980
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ORGANIC MAGNETIC RESONANCE, VOL. 16, NO. 1, 1981 TJ