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

Emergence of multidrug-resistant and extreme-drug-resistant strains of Mycobacterium tuberculosis (MTb) can cause serious socioeconomic burdens. Arabinogalactan present on the cellular envelope of MTb is unique and is required for its survival; access to arabinogalactan is essential for understanding the biosynthetic machinery that assembles it. Isolation from Nature is a herculean task and, as a result, chemical synthesis is the most sought after technique. Here we report a convergent synthesis of branched heneicosafuranosyl arabinogalactan (HAG) of MTb. Key furanosylations are performed using [Au]/[Ag] catalysts. The synthesis of HAG is achieved by the repetitive use of three reactions namely 1,2-trans furanoside synthesis by propargyl 1,2-orthoester donors, unmasking of silyl ether, and conversion of n-pentenyl furanosides into 1,2-orthoesters. Synthesis of HAG is achieved in 47 steps (with an overall yield of 0.09%) of which 21 are installation of furanosidic linkages in a stereoselective manner.

The occurrence of arabinofuranosides on the cell surface of Mycobacterium tuberculosis (Mtb) and their significance in controlling disease spurred interest in developing strategies for their diastereoselective synthesis. Mtb uses enzymes to achieve diastereoselectivity through noncovalent interactions. Of the two possible glycosidic linkages, chemically, 1,2-trans linkage is relatively easy to synthesize by taking advantage of neighboring group participation, whereas synthesis of the 1,2-cis linkage is notoriously difficult. In this article, stereochemical effects on the diastereoselectivity of arabinofuranosidation are investigated with thiopyridyl, imidate, and thiotolyl donors as well as differently crowded glycosyl acceptors; subtle differences in the stereochemical environment of the acceptors were observed to alter the diastereoselectivity of the furanoside formation. Results from this endeavor suggest that 1,2-cis arabinofuranosides can be synthesized conveniently by conducting the reaction at lower temperature on sterically demanding and less reactive substrates.

A simple, efficient, and practical method for the synthesis of C-2 deoxy-2-iodo glycoconjugates in self-assembled structures was found using PhI(OCOR)2. 2-Iodo glycoserinyl esters were intramolecularly converted into 2-iodo serinyl glycosides which upon dehalogenation gave C-2 deoxy amino acid glycoconjugates.

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