Iodocyclofunctionalization of (Z)-1-trichloroacetimidoyloxyalk-2-enes and 3-trichloroacetimidoyloxyalk-1-enes. Synthesis of (±)-erythro-sphinganine triacetate and (±)-threo-sphinganine triacetate

Abstract

(Z)-1-Trichloroacetimidoyloxyoctadec-2-ene, easily obtained from (Z)-octadec-2-en-1-ol, was iodocyclized with N-iodosuccinimide to give the 4-(1-iodohexadecyl)-2-trichloromethyl-4,5-dihydro-oxazole. From this compound, two routes were developed, either to pure (±)-erythro-sphinganine triacetate or to pure (±)-threo-sphinganine triacetate, respectively. The neutral cleavage of 4-(1-iodohexadecyl)-2-trichloromethyl-4,5-dihydro-oxazole gave the corresponding amide which, by treatment with Amberlyst A 26 (CO₃^2– form), afforded the cis-4-hydroxymethyl-5-pentadecyl-2-trichloromethyl-4,5-dihydro-oxazole together with a minor amount of cis-2-hydroxymethyl-3-pentadecylaziridine. After hydrolysis of the oxazole and full acetylation, (±)-erythro-sphinganine triacetate was obtained in 70% yield. On the other hand, acidic cleavage of the 4-(1-iodohexadecyl)oxazole 2-amino-3-iodo-octadecan-1-ol hydrochloride, which was directly treated with Amberlyst A 26 (AcO^– form). The product was acetylated and (±)-threo-sphinganine triacetate was recovered in 70% yield after chromatographic separation.

As an alternative, 3-trichloroacetimidoyloxyoctadec-1-ene was cyclized with N-iodosuccinimide to give a 20:80 cis:trans mixture of 4-iodomethyl-5-pentadecyl-2-trichloromethyl-4,5-dihydro-oxazoles. After ring cleavage, the corresponding ring-opened hydrochlorides were obtained. The mixture was then treated with Amberlyst A 26 (AcO^– form) and the product was directly acetylated. After silica gel chromatography, (±)-threo-sphinganine triacetate and (±)-erythro-sphinganine triacetate were obtained in good yield, in the ratio 80:20.