Synthesis of an optically pure indolizidine derivative

Abstract

Intermediate 3, a degradation product of a new indolizidine alkaloid Vincetene (1), was synthesized in optically pure form. Optically pure glutamate was coupled with 2,3-dimethoxynaphthalene and then cyclized to give pyroglutamate 18. Intramolecular Fridel-Crafts acylation of pyroglutamate 19 with tin tetrachloride in methylene chloride gave amido ketone 21 to the desired α-position of naphthalene ring. Reduction of ketone 21 with L-Selectride followed by deoxygenation of the resulting alcohol 22 produced amide 23 in high yield. Amide 23 was further reduced with lithium aluminum hydride to give the target compound 3 as a white crystalline solid. All the physical and spectral data (except optical rotation) of 3 was identical with those reported in the literature.