One‐Pot Synthesis of Hydrophobically Modified Iminosugar C‐Alkynylglycosides: Facile Synthesis of Polyhydroxy Tetrahydroindolizines

Abstract

A mild and efficient one-pot method has been developed for the stereoselective synthesis of structurally diverse novel iminosugar C-alkynylglycosides. The generality of this methodology has been demonstrated with a wide variety of amines and copper acetylides. This one-pot method has been exploited in the synthesis of new class of DNA cross-linking agents, polyhydroxy 1-vinyl-tetrahydroindolizine derivatives.

Copper‐Catalyzed A3‐Coupling for the Diversity‐Oriented Synthesis of Proline‐Derived Alkynyl‐Substituted Peptidomimetic Scaffolds

“…Similar results were obtained by using a chiral secondary amine, and modest increase in the stereoselectivity was ascertained using phenylalanine esters, giving the corresponding products 7 and 8 with similar diastereoselectivity of 8:1. The low yield of these product 7 was attributed to the side homo‐coupling reaction . This problem was bypassed using the corresponding tert ‐butyl ester for the achievement of 8 , which proved to be more resistant to the reaction conditions and not experiencing such side reaction.…”

Glycoside Mimics from Glycosylamines: Recent Progress

“…Alkynyl anions [71]: A further extension of this work allowed the introduction of an alkynyl group at the ‘pseudoanomeric’ position: in situ formation of the cyclic iminium ion as before followed by reaction with a terminal alkyne in the presence of a Cu(I) salt gives access to 1- C -alkynyl piperidine iminosugar derivatives 29 , in high yield and complete stereoselectivity (Scheme 11). …”

“…Owing to the rich chemistry of the nitromethyl group, 1- C -nitromethyl iminosugar derivatives constitute precursors of a wide variety of further glycoside mimics, as well as to novel polycyclic compounds. Several examples of further functionalization/cyclization by reactions of the nitromethyl group with the nitrogen substituent (allyl, propargyl) were reported by Baskaran and coworkers [71]. …”

A Short and Efficient Synthesis of Iminosugar 2‐Acyl Indolizidine

“…Interestingly, oxazolidine intermediate 30 , prepared from ribose tosylate 7 and amino‐propargyl alcohol 29 , underwent smooth aza‐Cope–Mannich cyclization with concomitant aerobic oxidation to furnish a tetrahydroindolizine based iminosugar derivative 32 in 78 % yield (Scheme ) . Intriguingly, conformationally locked pyrrole fused indolizidine and pyrrolizidine derivatives are known to exhibit biological activities …”

“…[9] Recently,w ereported amild and efficientm ethod for the one-pot synthesis of novel iminosugar C-glycosides via stereoselective arylation/alkynylation of in situ generated iminium ion. [10] Our enduring interest, in developing efficient methods for the synthesis of biologically active and pharmaceutically important molecules, [11] has motivated us to develop an ew and expeditiousr oute towards the synthesis of functionalizedi minosugar2 -acyl-indolizidines using the Overman protocol.…”