Methyl 1,2‐Orthoesters as Useful Glycosyl Donors in Glycosylation Reactions: A Comparison with n‐Pent‐4‐enyl 1,2‐Orthoesters

Abstract

Mannopyranose‐derived methyl 1,2‐orthoacetates (R = Me) and ‐benzoates (R = Ph) can function as glycosyl donors – upon BF3·Et2O activation in CH2Cl2 – in glycosylation reactions with monosaccharide acceptors to afford disaccharides in good yields. In the process, glycosylation is preferred to acid‐catalyzed rearrangement leading to methyl mannopyranosides. Methyl 1,2‐orthoesters can be also used in regioselective glycosylation protocols with monosaccharide diols, in which they display good regioselectivity.

Chemical O‐Glycosylations: An Overview

“…Fraser‐Reid and co‐workers also introduced mannopyranoside‐derived methyl orthoesters as possible donors for glycosylation. They underwent easy activation with the help of BF 3 ⋅Et 2 O and demonstrated proceedings analogous to that of NPOEs.…”

A Concise Synthesis of a BODIPY-Labeled Tetrasaccharide Related to the Antitumor PI-88

“…In those approaches, different types glycosyl donors have been employed. We have been interested in the use of 1,2-methyl orthoesters (MeOEs) [ 29 , 30 , 31 , 32 , 33 ] as an inexpensive alternative to Fraser–Reid’s n -pentenyl orthoester glycosyl donors (NPOEs) [ 34 , 35 , 36 ]. The former derivatives were shown to display good regioselectivity, similar to that of NPOEs [ 31 ].…”

“…We have been interested in the use of 1,2-methyl orthoesters (MeOEs) [ 29 , 30 , 31 , 32 , 33 ] as an inexpensive alternative to Fraser–Reid’s n -pentenyl orthoester glycosyl donors (NPOEs) [ 34 , 35 , 36 ]. The former derivatives were shown to display good regioselectivity, similar to that of NPOEs [ 31 ]. Accordingly, our convergent 1 + 1 + 2 approach to BODIPY-tagged tetramannan, 10 ( Scheme 1 ) was based on our previous studies on the selective mono-glycosylation at position O -3 in mannopyranose substrates possessing a 2,3,4 triol moiety, i.e., 6 , 7 ( Scheme 1 ), with MeOE glycosyl donors, 4a , 4b , and 9 [ 31 ] .…”

“…The former derivatives were shown to display good regioselectivity, similar to that of NPOEs [ 31 ]. Accordingly, our convergent 1 + 1 + 2 approach to BODIPY-tagged tetramannan, 10 ( Scheme 1 ) was based on our previous studies on the selective mono-glycosylation at position O -3 in mannopyranose substrates possessing a 2,3,4 triol moiety, i.e., 6 , 7 ( Scheme 1 ), with MeOE glycosyl donors, 4a , 4b , and 9 [ 31 ] . Thus, our strategy involved two glycosidic disconnections A and B ( Scheme 1 ).…”

A Malonyl-Based Scaffold for Conjugatable Multivalent Carbohydrate-BODIPY Presentations

“…Based on the well-studied chemistry of malonate diesters [58], the sequential bis-alkylation of dimethyl malonate ( 4 ) with pentenyl bromide and propargyl bromide paved the way to, previously unreported, ene-yne derivative 5 (Scheme 1). Subsequent LiAlH 4 -mediated reduction of 5 led to diol 6 , which was then glycosylated with readily prepared methyl orthoester (MeOE) 7 [59,60] (acid washed molecular sieves (AWMS), microwave irradiation) to furnish dimannan 8 in acceptable yield (Scheme 1) [60].…”