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

Abstract

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

A Versatile Synthesis of Pentacosafuranoside Subunit Reminiscent of Mycobacterial Arabinogalactan Employing One Strategic Glycosidation Protocol

“…The glycosidation between diol 8 and acceptor 32 was performed affording an inseparable mixture of pentasaccharides 35 . Earlier reports on the synthesis of pentasaccharide motifs indicated that the diastereomeric ratio would likely result from the C‐5 position of the aglycon due to its inherently more reactive nature compared with the C‐3‐OH . Temperature controlled glycosidations and reversing the addition sequence of glycosyl donor and acceptor did not improve the diastereoselectivity and, more frustratingly, the isomers could not be separated.…”

“…Now,t he stage was set for the gold/silver-catalysed glycosidation in a{ 2 2 + 1} fashion.T he glycosidation between diol 8 and acceptor 32 was performed affording an inseparable mixture of pentasaccharides 35.E arlier reports on the synthesis of pentasaccharidem otifs indicated that the diastereomericr atio would likely result from the C-5 position of the aglycon due to its inherently more reactive nature compared with the C-3-OH. [18,[21][22][23] Temperature controlled glycosidations and reversing the addition sequence of glycosyl donor and acceptor did not improvet he diastereoselectivity and, more frustratingly, the isomersc ould not be separated. Hence, sequential addition of the disaccharide was investigated and installation at the C-5 positionp rior to the C-3 positionw ould be beneficial because the mixtureo fc ompounds, if any,w as expected to be easy to purify.W ith this idea, orthoester 33 was saponified, monosilylated using 1.1 equivalent of TBDPS-Cl at 0 8Ca nd installation of the levulinoate protectionw as carried-out at the C-3 position to afford 36 in 61 %o ver three steps.…”

“…Nevertheless, synthesis of polylactosamine with 25‐saccharide residues by Ogawa and O ‐specific polysaccharide containing 24‐residues by Pozsgay were the conspicuous early efforts towards the synthesis of large oligomers. Of mycobacterial origin, mannose‐capped LAM fragment by Fraser–Reid, independent syntheses of docosaarabinofuranoside by Lowary and Ito, heneicosasaccharide (21‐residues) of LAM and AG syntheses by our group are some of the notable efforts in the literature that describe synthesis of large oligosaccharides. Lowary invoked salient features of trichloroacetamidates and thiotolyl donor chemistry, whereas Ito utilised thioglycosides for assembling the docosasaccharide .…”

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

“…The regio‐ and stereochemical issues are major challenges during glycans synthesis, and results in a time‐consuming and tedious process for carbohydrate synthesis . Indeed, examples of the synthesis of long, branched, and complex carbohydrate chains with over 15 units are still limited . Therefore, development of efficient strategies for the assembly of long, branched, and complex carbohydrate sequences is direly needed and remains one of the most challenging tasks for synthetic chemists.…”

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

“…[11,12] Indeed, examples of the synthesis of long,b ranched, and complex carbohydrate chains with over 15 units are still limited. [13][14][15][16][17][18][19][20] Therefore, development of efficient strategies for the assembly of long, branched, and complex carbohydrate sequences is direly needed and remains one of the most challenging tasks for synthetic chemists.…”