Photoinitiated Thiol‐ene Reactions of Enoses: A Powerful Tool for Stereoselective Synthesis of Glycomimetics with Challenging Glycosidic Linkages

Abstract

Thioglycosides and C-glycosidesr epresent pharmacologically useful classes of glycomimetics that possess ah igh degree of biological stability. One emerging tool for the stereoselective synthesis of thioglycosides is the photoinitiateda ddition of thiols to unsaturated sugars. Moreover,t hiyl radical-mediated reactions of exo-glycals and 1-substituted endo-glycalso ffer facile routes to b-Cglycosidic structures. This Concepta rticle summarizes the thiol-ene coupling strategies developed recently by our group andS omsµk'sg roup for the synthesis of several kinds of glycomimetics which are difficult to synthesize by conventionalm ethods. One unusual characteristico ft he thiol-ene reactions of endo-glycals is that heating inhibits, whereas cooling promotes the reaction. This unique temperature dependence as well as the effects of the enose structures and thiol configurations on the efficacya nd stereoselectivityo ft he reactions are also discussed.[a] Prof.

Synthesis of Thiodisaccharides Bearing N‐Acetylhexosamine Residues: Challenges, Achievements and Perspectives

“…[100] 2-Acetoxyglycals, in turn, led stereoselectively to 1,2-cis-α-linked thiodisaccharides, which are difficult to obtain through other methods. Borbás [103] showed that many short cycles of Scheme 36. Free radical thiol-ene reaction with exocyclic double bonds, dr: diastereomeric ratios.…”

“…[102] It should be mentioned that Borbás recently published an excellent review which collects all the latest results on the photoinitiated thiol-ene reactions involving unsaturated sugars as precursors, portraying this method as a powerful tool for the construction of thiodisaccharides. [103]…”

“… [100] 2‐Acetoxyglycals, in turn, led stereoselectively to 1,2‐ cis ‐α‐linked thiodisaccharides, which are difficult to obtain through other methods. Borbás [103] showed that many short cycles of irradiation with repeated additions of the photosensitiser resulted more beneficial than long‐time irradiation periods.…”

Synthesis and photoinitiated thiol–ene reactions of exo-mannals – a new route to C-β-d-mannosyl derivatives

“…[17][18][19][20] In carbohydrate chemistry, the sugar moiety can be used both as a thiol or an alkene components, and such transformations show excellent regio-and stereoselectivities. 21 The hydrothiolation of exo-glycals allows the synthesis of novel, glycosylmethyl sulde (Gly-CH 2 -SR) type mimetics with very high or exclusive b-selectivity. [22][23][24][25] Based on the above experiences we set out to study the thiolene additions with various exo-mannals with the expectation that the b-stereoselectivity observed with other exo-glycal congurations will be maintained here as well.…”

Synthesis of Potential Glycosyl Transferase Inhibitors by Thio‐Click Reactions

“…We have recently demonstrated that 1,2-cis-α-linked thioglycosides can be prepared with complete stereoselectivity by the photoinitiated, radical mediated thiol-ene coupling reaction (also known as a thio-click reaction) [11] of readily available 2substituted glycals. [12][13][14][15] The radical mediated thiol-ene coupling is known to proceed in a regioselective way to produce an anti-Markovnikov-type thioether, and in the case of substituted cyclic alkenes the addition occurs with high or complete stereoselectivity in a trans-diaxial manner via an axial attack of the thiyl radical onto the double bond followed by an axial hydrogen abstraction of the intemediate carbon-centered radical from the thiol. [13,15] Thus, the thio-click approach offers a simple and completely stereoselective way for the preparation of stable thio-linked analogues of the challenging 1,2-cis α-Oglycosides such as the sugar α-O-phosphates in UDP-sugars (Scheme 1A).…”