Expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the Mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors

Herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (2 mmol) was added to a rapidly stirred solution of alcohol (1 mmol) in CH 2 Cl 2 -MeOH (1:4) at 25 o C. After 4 h, the reaction mixture was quenched by the addition of Et 3 N (reaction mixture turns black from brown) and solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexanes) to furnish the alcohol as a pale yellow coloured syrup.
Procedure L: Synthesis of 1,2-acetonide of arabinose: 2,2-Dimethoxy propane (1.25 mmol) and PTSA (0.2 mmol) were added to a vigorously stirring solution of C-5-O-TBDPS arabinofuranoside (1 mmol), activated 4Å MS in anhydrous CH 2 Cl 2 (50 mL) and stirred for 24 h at 25 o C. After completion of the reaction, excess Et 3 N was added, the solid residue was filtered off through Celite ® bed. The solvent was evaporated in vacuo under reduced pressure and the crude compound was purified by column chromatography (ethyl acetate/hexanes) to obtain the desired araf-1,2-acetonite.

Procedure M: Synthesis of benzoates:
S6 A solution of the alcohol (1 mmol) in anhydrous pyridine (10 mL) and DMAP (0.1 mmol) was cooled to 0 °C under nitrogen atmosphere and benzoyl chloride (1.2 mmol per alcohol) was added dropwise and stirred for 5 h at 25 o C. The reaction mixture was poured into cold water with vigorous shaking, neutralized by the addition of 6N HCl solution, extracted with ethyl acetate (3x50 mL) and combined EtOAc layers was washed with cold water, sat. NaHCO 3 , brine solution, and dried over Na 2 SO 4 . The EtOAc solution was decanted and evaporated in vacuo to obtain a reddish brown coloured residue that was purified by column chromatography (ethyl acetate/hexanes) to obtain the required benzoate.

Procedure N: Saponification of benzoates:
Freshly prepared NaOMe (0.1 mmol per benzoate) was added to a solution of the benzoate (1 mmol) in MeOH (10 mL) and stirred for 8 h at 25 o C. The reaction mixture was concentrated in vacuo to obtain a residue that was purified by column chromatography (ethyl acetate/hexanes) to obtain alcohol.

Procedure O: Hydrogenolysis of compound 46:
To a solution of the compound 46 (30 mg, 5.4 µmol) in 2 mL of MeOH-THF-H 2 O (4:3:3) under Hydrogen atmosphere (balloon pressure) was added 10% Pd(OH) 2 (2mg, 1.0 µmol) and stirred for 36 h at 25 o C. The reaction mixture was filtered through a pad of Celite® and the filtrate was evaporated in vacuo first and subsequently subjected to lyophilisation to afford the target compound 47 (14 mg, 90%) as a white solid.