Spiroketal Synthesis. — A Case of Intramolecular Glycoside Bond Formation

Abstract

From 4-0-unsubstituted glucose derivatives 1 a, b the 4-hydroxymethyl-substituted glucose derivatives 9 a, b were obtained via oxidation to the ketone, Wittig reaction with methylenetriphenylphosphorane, borane addition, and subsequent oxidation to yield the diastereomeric galactose-derived compounds 5a. b; the required inversion of configuration at C-4 was accomplished through oxidation to the formyl derivatives, base-catalyzed isomerisation, and then reduction. Transformation of hydroxymethyl derivatives 9a, b into the iodo derivatives l l a, b and reaction with n-butyllithium generated the C-lithiated species l l a A , bA which furnished with 0-benzyl-protected gluconolactone 12 the ketose derivatives 13a, b. Treatment with EtzO -BF, afforded under concomitant 6-0-debenzylation the spiroketals 15a. b. Hydrogenolytic 0-debenzylation and subsequent 0-acetylation led to compounds 16a and 16b, respectively. The anomeric ketoside configuration was derived from NOE experiments.In our recent endeavours to synthesize methylene-bridged C-disaccharides two approaches, namely a C6-nucleophile + C7-electrophile and a C6-electrophile + C7-nucleophile route, respectively, have been employed[' -' I (Scheme 1). For the latter approach a rigid 'Cq conformer, as shown in the 1,6-anhydro derivative of type A, was selected as the C7-nucleophile because the 4C1-derived conformer of type B exhibited undesired interactions between the 6-oxygen of the B moiety and the newly formed anomeric ketose center of the gluconolactone moiety, utilized as C6-electrophile[2,'1; thus, intramolecular ketoside formation was observed as the only reaction. We would like to report on this finding which has not only bearing on new methods for intramolecular glycoside bond f~r m a t i o n [~,~] but also for the design of macrolide syntheses and other related natural p r o d~c t s [~,~] .

Hydrogen Atom Transfer Experiments Provide Chemical Evidence for the Conformational Differences between C‐ and O‐Disaccharides

“…Under oxidative conditions the expected 1,3‐dioxocane 18 coming from the abstraction of the H‐5′ was isolated, but only in 30 % yield (Scheme ). The major product was now the dioxaspirobicycle 19 generated by 1,6‐HAT between the alkoxyl radical and the hydrogen at C‐1′ 14. Moreover, two minor iodinated compounds 20 and 21 which were plausibly formed by two consecutive hydrogen abstractions were also isolated.…”

The UDP-Galp mutase catalyzed isomerization: synthesis and evaluation of 1,4-anhydro-β-d-galactopyranose and its [2.2.2] methylene homologue

“…Our data were not in agreement with the literature in 1 H-NMR assignments of 2-H and 6b-H in 18 and the optical rotation of 21. 77 Based on 1 H-NMR analysis (J 2,3 ~10 Hz), the predominant pyranoside conformation of 20-22 in D 2 O was assigned to be 4 C 1 . Thus our chemical modifications at C-4 of the hexoses did not change the conformational distribution of these compounds.…”

Glycosylations of Tertiary Alcohols: Synthesis of Fully Protected Disaccharides with Sterically Demanding Groups Attached to the Sugar Core

“…12 Nucleophilic attack of several organolithium species to the ketone 4 afforded the monosaccharide units with tertiary hydroxy groups in moderate to good yields (55-80%) as depicted in Scheme 1. In all cases diastereomeric mixtures of the gluco-and the galacto-configured sugar derivatives 5-8 were obtained that could be easily separated by silica gel column chromatography or preparative HPLC using a reversed-phase column.…”

“…The use of peracetylated trichloroacetimidates 14 as disarmed donors proved to be more successful. We tested a variety of glycosyl trichloroacetimidates such as the ones derived from rhamnose (10), galactose (11), glucose (12) and glucosamine (13). These electron-poor building blocks reacted with the respective sterically hindered acceptors to afford disaccharides 15-24 in moderate yield (27-62%) after activation with the Lewis acid TMSOTf.…”