A Study of the Epoxidation of 6-Deoxyhex-5-enopyranosides. 1,5-Dicarbonyl Derivatives and Novel Synthetic Routes to d-xylo-Hexos-5-ulose and d-lyxo-Hexos-5-ulose

Abstract

The work described deals with the isolation and characterization of epoxides from 6-deoxyhex-5-enopyranosides and preliminary exploration of their synthetic potential. Prolonged epoxidation reaction times led to their hydrolysis in situ and gave novel protected D-hexos-5-ulose derivatives (sugar 1,5-dicarbonyls). Some reactions of the hexos-5-uloses were studied, and in some cases septanoside (seven-membered-ring saccharide) derivatives were isolated. Novel routes to D-xylo-hexos-5-ulose and D-lyxo-hexos-5-ulose, of interest as intermediates in the synthesis and biosynthesis of inositols and aza sugars, are also described. The structures of the epoxides and novel hexos-5-uloses were established by NMR and X-ray crystallographic methods.

Display of Rich Reactivities of Endo‐ and Exocyclic Unsaturated Sugars that Parallel the Native Sugars

“…The reactivity profiles could thus be verified with the synthesis of such novel septanoside sugar derivatives [30] . Whereas ring expansion of pyranose to a septanose through one‐carbon homologation was developed herein, many innovative synthetic methods have been reported for their synthesis in contemporary literature [31‐35] …”

The Construction of Anhydro Monosaccharides

“…Their subsequent reaction scope studies revealed that the method could effectively convert various unprotected sugars to their 1,6‐anhydro analogs with the exception of two cases: 1) d ‐mannose, 2‐deoxy‐ d ‐glucose, and 2‐fluoro‐2‐deoxy‐ d ‐glucose gave no dehydrated products, which could be rationalized by the above mechanism; 2) the method was not effective for sugars with substitution at the C3‐position, which indicates the stereo‐hindrance on C3 is closely related to the occurrence of 1,6‐cyclization. The epoxide intermediate was also used by Enright and co‐workers to synthesize a series of 5‐ketohexoses with internal 1,6‐ether bridges . They suggested an 5,6‐epoxide as a key intermediate ( 24 ) from 2,3,4‐tri‐ O ‐protected‐6‐deoxyhexo‐5‐enopyranosides ( 23 ; 5,6‐ exo ‐glucal).…”

Analysis of the conformations of septanoside sugars

“…These are: (i) hemiacetal and acetal formation of a synthon containing aldehyde and appropriately positioned hydroxyl group [12][13][14][15][16][17][18][19]; (ii) cyclization and epoxidation of 6-deoxy hex-5-enopyranoside [20]; (iii) Knoevenagel condensation of sugar aldehyde with active methylene compounds [21,22]; (iv) Baeyer-Villiger oxidation of inositol derivatives [23]; (v) electrophile-induced cyclization of sugar derived alkenes [24]; (vi) Grignard reaction of vinyl magnesium bromide with suitably protected glucose and glucosyl amine derivatives [25,26]; (vii) acid-catalyzed cyclization of protected enitols [27,28]; (viii) metal-catalyzed cyclizations of sugar derived dienes, primarily, ring closing metathesis reactions [29][30][31][32];…”