Recent studies on reaction pathways and applications of sugar orthoesters in synthesis of oligosaccharides

Abstract

Abstract-Formation of sugar-sugar orthoesters consisting of a fully acylated mono-or disaccharide donor and a partially protected mono-or disaccharide acceptor is regioselective, and rearrangement of the orthoesters via RO-(orthoester)C bond cleavage gives a dioxolenium ion intermediate leading to 1,2-trans glycosidic linkage. The activity order of hydroxyl groups in the partially protected mannose and glucose acceptors is 6-OH > 3-OH > 2-or 4-OH. The coupling reactions with acylated glycosyl trichloroacetimidates as the donors usually give orthoesters as the intermediates specially when the coupling is carried out at slowed rates, and this is successfully used in regio-and stereoselective syntheses of oligosaccharides. Mannose and rhamnose orthoesters readily undergo O-2-(orthoester)C bond breaking, and this is used for synthesis of a-(1!2)-linked oligosaccharides. (1!3)-Glucosylation is special since the rearrangement of its sugar orthoester intermediates can occur with either RO-(orthoester)C bond cleavage with formation of the dioxolenium ion leading to 1,2-trans linkage, or C-1-O-1 bond cleavage leading to 1,2-cis linkage, and this is dependent upon the structures of donor and acceptor that compose the orthoester.

New Principles for Glycoside‐Bond Formation

“…The orthoester intermediates thus obtained can be transformed in situ into the desired glycosides by the addition of more of the catalyst, by extending the reaction time, or by other means. [103] This rearrangement usually leads to 1,2-trans glycosides through different possible pathways [104] and was used to develop new strategies for the regio-and stereoselective synthesis of oligosaccharides. [105] Nevertheless, additional studies, most notably by Wu and Kong, revealed that the rearrangement can also give 1,2-cis-linked products [106] in a transformation that does not conform with the classical concept of neighboring-group participation.…”

Synthesis and Biological Studies of 35‐Deoxy Amphotericin B Methyl Ester

“…[8] Orthoesters can be rearranged under acidic conditions to afford the corresponding glycoside. [9] However, the resilience of the orthoester and the acid sensitivity of the unsaturated alcohol combined to impair our efforts in this direction. For example, the use of a wide range of acids returned starting orthoester (e.g.…”

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

“…Activation of a mixture of alcohol 14 and trichloroacetimidate 16 at 0 °C with 0.1 equiv of BF 3 ·Et 2 O provided disaccharide 26 in only 21% yield, with a 1,2-glycosyl orthoester as the major product (40%). Orthoesters are common by-products of glycosylation reactions and typically rearrange under acidic conditions to give trans -linked glycosides [43]. Thus, 14 and 16 were treated with 0.25 equiv of an alternative Lewis acid, TMSOTf, and allowed to react for a longer time to allow the intermediate orthoester to isomerize.…”