De Novo Asymmetric Synthesis of All-d-, All-l-, and d-/l-Oligosaccharides Using Atom-less Protecting Groups

Abstract

Oligosaccharide synthesis is hindered by the need for multiple steps as well as numerous selective protections and deprotections. Herein we report a highly efficient de novo route to various oligosaccharide motifs, of use for biological and medicinal structure activity studies. The key to the overall efficiency is the judicious use of asymmetric catalysis and synthetic design. These green principles include the bidirectional use of highly stereoselective catalysis (Pd(0)-glycosylation/post-glycosylation). In addition, the chemoselective use of C-C and C-O π-bonds functionality, as atom-less protecting groups as well as an anomeric directing group (via a Pd-π-allyl), highlights the atom economical aspects of the route to a divergent set of natural and unnatural oligosaccharides (i.e., various D-/L-diastereomers of oligosaccharide as well as deoxysugars which lack C-2 anomeric directing groups). For example, in only 12 steps, the construction of a highly branched hepta-saccharide with 35 stereocenters was accomplished from an achiral acylfuran.

N‐Heterocyclic Carbene Catalyzed Dynamic Kinetic Resolution of Pyranones

“…Inspired by the role of 6-hydroxy-3-pyranones as key intermediates for carbohydrate synthesis, [10] ODoherty [11] and co-workers have disclosed an elegant palladium-catalyzed stereospecific glycosidation [11][12][13] of 3-pyranones with an ester substituent in the 5-position (Scheme 1a)f or assembling diversified libraries [14] and complex natural products. [15] Because of the significance of pyranones with as ubstituent (e.g.,e sters) in the 6-position, many efforts have been devoted to the manipulation of the hemiacetal group of pyranones,for example,bythe protection or oxidation of the hemiacetal group.…”

Merremoside D: De Novo Synthesis of the Purported Structure, NMR Analysis, and Comparison of Spectral Data

“…We have demonstrated that a de novo approach to carbohydrates 6 can be used for the assembly and medicinal chemistry study of oligosaccharides. 7, 8 The approach combines the use of asymmetric synthesis of pyranone glycosyl donor 5 , a Pd(0)-catalyzed glycosylation and post-glycosylation transformation, which allow the enone functionality of the pyranones to serve as atom-less protecting groups for the C -2 to C -4 triol portion of the target rhamno -pyranose. Because the route uses asymmetric synthesis, it offers equal efficiency to access to various all D-, all L- and mixed D/L-isomer.…”

Application of the Wharton Rearrangement for the de novo Synthesis of Pyranosides with ido, manno, and colito Stereochemistry

“…As we have previously reported, Boc‐pyranones 9a and 9b were obtained optically pure from furans 1a and 1b in three steps by Noyori atom‐transfer asymmetric reduction13 [formic acid/Et 3 N, ( R )‐Ru(η 6 ‐mesitylene)‐( S , S )‐TsDPEN], Achmatowicz cyclization (NBS, H 2 O), and tert ‐butoxycarbonylation with Boc 2 O (Scheme ) 14. Palladium‐catalyzed glycosylation with benzyl alcohol resulted in benzyl pyranones 2a and 2b .…”