A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

Andrea Goti,Stefano Cicchi,Alberto Brandi,Valentina Fedi,Franca M Cordero

doi:10.3390/40100001

Andrea Goti, Stefano Cicchi + Show 3 more

Open Access

https://doi.org/10.3390/40100001

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Journal: Molecules (Basel, Switzerland)	Publication Date: Dec 22, 1998
Citations: 40	License type: CC BY 3.0

Affiliation: University of Florence

Abstract

Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and g-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)- lentiginosine.

Highlights

IntroductionNitrones have been recently the subject of intense research efforts, because of the wide role played in the synthesis of complex molecular frameworks
The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and γcrotonolactone were converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors
The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)lentiginosine

Summary

Introduction

Nitrones have been recently the subject of intense research efforts, because of the wide role played in the synthesis of complex molecular frameworks They display reactivity either as 1,3-dipoles in Molecules 1999, 4 cycloaddition reactions towards structurally differentiated dipolarophiles [1] as well as electrophiles towards attacking organometal counterparts [2]. Both the reactions give rise to the formation of new carbon-carbon bonds, often with a high degree of stereocontrol. Recent years have witnessed a renewed interest in this chemistry, mainly due to the development of methods for the preparation of enantiomerically pure nitrones and their subsequent application in synthesis In this context, enantiopure cyclic nitrones have proved useful [5].

Results

H OtBu HO

Conclusion