Total synthesis of the amaryllidaceae alkaloids, lycorine and zephyranthine

Abstract

A synthesis of lycorine and zephyranthine was accomplished starting from 3,r-4,c-4a,5,6,t-10b-hexahydr o-6-oxophenanthridine-4-carboxylic acid (VI). Homologation of the acid by the Arndt–Eistert reaction gave the homoester (VII), which was also obtained by cyclisation of methyl c-2-(N-methoxycarbonyl)-t-3-(3,4;methylenedioxyphenyl)cyclohex-4-enyl-r-acetate (VIII). Reduction of (VII) with lithium borohydride gave the alcohol (IX). After converting the alcohol function to the chloride and the lactam group to the imino-ether, the resulting imino-ether chloride was cyclised to r-3a,c-3b,4,5,7,t-1 1 b-hexahydro-9,10-methylenedioxy-7-oxo-3H-pyrrolo[3,2,1-de]phenanthridine (XI), which was alternatively obtained by lithium aluminium hydride reduction of 5,7dioxo-3,r-3a,c-3b,4,5,t-11b-hexahydro-9,10-methylenedioxy-7H-pyrrolo[3,2,1-de]phenanthridine (XIV) under controlled conditions. Epoxidation of (XI) gave stereoselectively the α-oxide (XV). Repeated application of Sharpless' method to convert epoxide into allyl alcohol [using selenophenol on the 1,2-α-oxide (XV) and 1-acetyl 2,3-β-oxide (XXIV)] gave the lycorine lactam (XXV). Lithium aluminium hydride reduction of the diacetyllycorine lactam gave lycorine. Osmium tetraoxide treatment of (XI) gave two stereoisomeric glycols, one of which yielded, on lithium aluminium hydride reduction, zephyranthine.