Synthesis of Building block 3

SPh
OH OAc
O O
O a. O b. AcO + AcO SPh
HO AcO
AcO AcO
HO AcO OAc OAc
OH OAc 3 3
1 2

a. Ac2O/I2; b. PhSH, BF3.OEt2, DCM

1. Synthesis of Rhamnose peracetate 2 (step a)

L-Rhamnose hydrate was dissolved in Ac2O and catalytic amount of Iodine was added, stirred
until completion. Mixture was concentrated in vacuum, and resulting crude was dissolved in DCM,
washed with NaHCO3 and Na2SO3, layers separated and aqueous dried and concentrated to dryness.

2. Synthesis of 1-thiophenyl-Rhamnose peracetate 3 (step b)

Rhamnose peracetate and thiophenol were dissolved in DCM, BF 3.OEt2 was dropwise added,
reaction was stirred at r.t until completion. Once reaction was done, it was poured into a saturated
solution of sodium bicarbonate. Layers were separated and organic dried and concentrated.

Crude was purified by SiO2 Chromatography (Hex/EtOAc). 3 fractions were collected, Main is 3
(75%), mixture (11%) and 3 (14%)

Synthesis of Building block 5

SPh SPh SPh

O c. O
d. O
AcO HO BzO
AcO HO HO
OAc OH OBz
3
4 5

c. NaOMe, MeOH; d. (1) PhC(OEt)3, pTsOH, ACN; (2). BzCl, Pyr; (3) AcOH (80%), 80`C.

3. Synthesis of 1-thiophenyl-Rhamnose 4 (step c)

Compound 3 was suspended in MeOH, and catalytic amounts of NaOMe 0,5M was added,
reaction stirred until completion. Quenched with H + resin, filtered and concentrated to dryness.

4. Synthesis of 1-thiophenyl-2,4-Dibenzoyl-Rhamnose 5 (step d)

Compound 4 was dissolved in ACN, triethyl orthobenzoate was added. Once reaction was
complete triethylamine was added and concentrated to dryness. Resulting crude was dissolved in DCM,
pyridine was added followed by Benzoyl Chloride.

Solids were fitltered, and washed with DCM, Filtrate was concentrated to dryness, redissolved in
EtOAc, washed with HCl (2N) and water. Concentrated again to furnish an oily crude that was treated in
AcOH/H2O 8/2 at 80`C for 2 hours. Volatiles were removed in rotovap and crude purified by SiO2
Chromatography (Hex/EtOAc).

Synthesis of Building block 8

SPh SPh SPh

O c. O e. O
AcO HO BnO
AcO HO HO
OAc OH OH
3 4 6

OP(O)(OBu)2
SPh SPh
f. O g. O h. O
BnO BnO BnO
BnO BnO BnO
OH OLev OLev
7 9
8 

c. NaOMe, MeOH; e. (1) 2,2-DMP, pTsOH, ACN; (2). BnBr, NaH, DMF; (3) AcOH (80%), 80`C; f. (1) Bu2SnO,
Tol; (2) CsF, BnBr, DMF; g. LevOH, DIC, DMAP, DCM; h. HOP(O)(OBu)2, NIS, TfOH, DCM, 4A MS.

5. Synthesis of 1-thiophenyl-4-benzyl-Rhamnose 6 (step e)

Compound 4 was dissolved in ACN, 2,2-dimethoxypropane was added followed by catalytic

amounts of pTsOH, once the protection was done, it was concentrated to dryness and dissolved in DMF.
Resulting solution was cooled in an ice bath and NaH (60%) was added, followed by Benzyl Bromide.

Once reaction was done, It was quenched with acetic acid, DMF removed on high vacuum.
Resulting crude was purified by SiO2 Chromatography (Hex/EtOAc), and product obtained was
hydrolyzed with AcOH (80%) at 80`C. Concentrated to dryness and product crystallized in hot ethanol.

6. Synthesis of 1-thiophenyl-3,4-dibenzyl-Rhamnose 7 (step f)

Compound 6 was dissolved in Toluene, Bu2SnO was added and solvent was distilled to remove
water azeotropically. Cooled to r.t. a concentrate to dryness in rotovap. Resulting intermediate was
dissolved in DMF, Benzyl Bromide was added followed by CsF, stirred at r.t. overnight.

Solids were filttered off and washed with EtOAc, filtrate was concentrated in high vacuum and
crude purified by SiO2 chromatography.

7. Protection of compound 7 with LevOH (step g)

Compound 7, and LevOH was dissolved in DCM, DIC was added followed by catalytic amounts of
DMAP. After 3h reaction was done, solids filtrated off, washed with DCM. Concentrated to dryness and
purified by SiO2 Chromatography (Hex/EtOAc)
 SPh

OP(O)(OBu)2 SPh O
BzO
O O i. O
BnO + BzO OBz
BnO HO O
OLev OBz BnO 10
9 5 BnO
OLev
SPh SPh
SPh
O O
BzO BzO
j. O
O O BzO
OBz OBz O
OBz
O 10 O
BnO BnO
11 O
BnO BnO BnO
OLev OH
i. BnO
O
13
OP(O)(OBu)2 O
SPh BzO
O
O OBz
O BzO
BzO h. O
O BnO
O OBz
OBz
BnO
O OLev
O 10 BnO 12
BnO
BnO
BnO OLev
OLev

h. HOP(O)(OBu)2, NIS, TfOH, DCM, 4A MS.; i. TMSOTf, DCM, 4A MS; j. NH2NH2.HOAc, Tol/EtOH.

8. General procedure for the synthesis of Phosphate Donors 9 & 12 (step h)

Dibutyl Phosphate and donor (8 or 10) were mixed in dry DCM along with 4A Molecular sieves.
Mixture cooled in an ice bath and NIS was added followed by Triflic Acid. Stirred in cold under inert
atmosphere until disappearance of donor. Quenched with NaHCO 3/Na2SO3 solution, filtered, layers
separated and organic dried, concentrated and purified by SiO 2 Chromatography (Hex/EtOAc).

9. General procedure for the coupling of phosphate donors to acceptors, Synthesis of compounds 10
and 13 (step i)

Phosphate donor (9 or 12) and acceptor (5 or 11), were mixed in anhydrous DCM along with 4A
M.S. Mixture was cooled to -40`C before adding TMSOTf. Stirred in cold until disappearance of
phosphate. Quenched with NaHCO3 (sat), filttered layers separated and organic dried, concentrated and
purified by SiO2 Chromatography (Hex/EtOAc)
 6 6
6
O N3 O N3
O N3

O O
BzO O BzO
BzO
O
OBz j, k O j, k O
OBz
OBz
O O
BnO O BnO
BnO
BnO BnO
OLev BnO 5
3 OLev
OLev

10. General procedure for removal of Levulinic Group, Synthesis of 11 and polisaccharides acceptors
(step j)

Levanic esters were dissolved in a Tol/EtOH mixture, Hydrazine acetate was added and stirred at
r.t until completion. Solvents removed under vacuum and residue purified by SiO 2 Chromatography.
(Hex/EtOAc)

11. General Procedure for coupling of thiophenol donors to 2-OH acceptors, Synthesis of
polisaccharides (step k)

Thiophenol Donors 10 or 13 were mixed in DCM with free OH acceptors and 4 A M.S. cooled to
0`C, NIS was added followed by TfOH. 1h later reaction was quenched with NaHCO 3 (sat) and Na2SO3,
filtered, layers separated and organic dried and purified by SiO 2 Chromatography (Hex/EtOAc)