A Convergent and Stereocontrolled Synthetic Route to the Core Pentasaccharide Structure of Asparagine-Linked Glycoproteins

Intramolecular aglycon delivery

“…[17][18][19][20][21][22][23][24][25][26][27] Tethering proceeded very efficiently using a slight excess of either donor or acceptor (typically 1.1-1.4 equiv relative to the other component) to give mixed acetals, which were either purified by size-exclusion chromatography or used crude in the next step. Activation with MeOTf, DTBMP, 4 Å in DCE or DCM gave the b-mannosides exclusively.…”

Elaboration of Monoarabinofuranosidic Building Blocks

“…[25,26] A much better precursor to glycosyl donors (α and β), however, was compound 18, obtained in 64% yield from orthoester 6. Monoprotection of the primary position of the ring was easily accomplished with TBDPSCl, to give 22 in 80% yield, or with pivaloyl chloride in pyridine, to give 25 (65%).…”

“…This left the introduction of the controlling element for the glycosylation on the 2-hydroxy group of the arabinose ring at the very last stage of the synthesis of the donors. Introduction of the 4-methoxybenzyl ether [25,26] was found to be difficult. Under standard benzylation conditions (NaH, 4-MeOBnCl, DMF) or with use of phase-transfer catalysis (4-MeOBnCl, Bu 4 NHSO 4 , aqueous NaOH) [43] almost complete degradation of starting material was observed, and compound 23 was only isolated in very low yields.…”

“…Among the numerous methods available for IAD, the procedure described by Ogawa, [25,26] which uses the 4-methoxybenzaldehyde acetal as a temporary tether, seemed to us to be the most convenient: products are easily prepared, they are stable, and this methodology has been shown to work for furanoside synthesis. [12,28,29] This first paper deals with the preparation of arabinofuranoside building blocks from orthoesters of arabinose, while applications to the synthesis of various structural motifs of mycobacterial arabinans, including the terminal pentasaccharide of arabinogalactan and the caps of the LAM of M. tuberculosis, will be reported in the near future.…”

Double Asymmetric Induction During Intramolecular Glycosylation

“…However, the prediction of the stereosyl donor and a glycosyl acceptor are connected by a temporary, labile tether, which is cleaved in the course of the selectivity of these intramolecular glycosylations via prearranged glycosides still remains somewhat confusing since formation of the O-glycosidic bond. In this approach, dialkylsilyl [ [7] and acetal tethers [8] [9] [10] [11] [12] [13] various factors (i.e. type and position of the bridging group, of the glycosyl donor, and of the acceptor) can influence have been succesfully used.…”