A versatile stereocontrolled synthesis of 2-deoxyiminosugar C-glycosides and their evaluation as glycosidase inhibitors.

A highly enantioselective synthesis of (R,S) or (S,S)-2,6-disubstituted dehydropiperidines has been previously achieved through Sn/Li transmetalation of the corresponding stannylated dehydropiperidines or of their precursors. Herein, we successively consider their Upjohn's syn dihydroxylation and their anti-dihydroxylation via an epoxidation reaction followed by epoxide opening reaction. The stereochemical course of these reactions was first reported including the use of appropriate protecting groups before considering the conversion of the obtained compounds into NH or NMe iminosugar hydrochlorides. A primary evaluation of the designed iminosugar C-glycosides as glycosidase inhibitors suggests candidates for the selective inhibition of α-galactosidase, amyloglycosidase and naringinase. Beyond the reported results, the method constitutes a highly modulable route for the synthesis of well stereodefined iminosugar C-glycosides, an advantage which might be used for the design of iminosugars to enhance their biological properties.

Preparation of enantiomerically enriched α-aminoorganostannanes and their applications in stereoselective synthesis.

This review deals with the preparation of chiral, nonracemic α-aminoorganostannanes and their applications in asymmetric synthesis. The pioneering works in this field date back almost 20 years ago and since then extensive research has been carried out to develop efficient and selective routes to highly enantioenriched α-aminoorganostannanes. The facile Sn/Li transmetalation of these compounds by n-BuLi has led to various applications in stereoselective synthesis. Selected examples using chiral α-aminoorganostannanes as starting materials will be reported.

Synthesis of highly enantioenriched chiral alpha-aminoorganotins via diastereoselective ring opening of chiral N-(arenesulfonyl) 2-tributylstannyloxazolidines.

trans-N-(Arenesulfonyl)-2-tributylstannyloxazolidines derived from (R)-phenylglycinol were diastereoselectively ring-opened by soft organometallic reagents in the presence of BF(3).OEt(2). Both higher order organocuprates and allyltributyltin afforded the desired products in good-to-excellent yields and high diastereoselectivities (dr up to 99/1). The stereochemical assignments of tributylstannyl-beta-aminoalcohols were firmly established from NMR data and after determination of several radiocrystallographic structures. Mechanisms were proposed in order to rationalize the observed selectivities.

Stereodivergent synthesis of iminosugars from stannylated derivatives of (S)-vinylglycinol.

An original access to iminosugars from a cis/trans mixture of stannylated oxazolidinones 5 is reported. The dehydropiperidines 7-trans and 7-cis were obtained stereoselectively with an RS and SS configuration depending on the order of the Sn-Li transmetalation (followed by electrophilic trapping) and of the ring closing metathesis reactions due to the stereoselective epimerization of the α-aminoanion intermediate. The dehydropiperidines 7-trans and 7-cis were subsequently used for the synthesis of enantiopure homonojirimycin analogs.

Electrochemical cleavage of sulfonamides: an efficient and tunable strategy to prevent ß-fragmentation and epimerization.

The electrochemical reduction of sensitive sulfonamides is described. The addition of a benzoyl group on the nitrogen atom facilitates the reductive cleavage of sulfonamides preventing ß-fragmentation and epimerization. This strategy was successfully applied to the cyclopropylamine and to α-amino stannanes.

Preparation of gamma-siloxyallyltributylstannanes and their use in the synthesis of (+/-)-1-deoxy-6,8a-di-epi-castanospermine.

gamma-siloxyallyltributylstannanes were selectively obtained as E or Z isomers from beta-tributylstannylacrolein upon reaction with lithium or magnesium alkylcyanocuprates. The ability of the reagents to give a high syn selectivity when added to iminium salts has been used for the efficient synthesis of (+/-)-1-deoxy-6,8a-di-epi-castanospermine from succinimide. The key step of the synthesis was the allylstannation of the N-allyliminium intermediate followed by ring closing metathesis.