| Isocelorbicol is one of a number of complex, polyhydroxylated derivatives of agarofuran which are found in many plants of the family Celastraceae. Several ester alkaloids based on these sesquiterpenes have been isolated from Catha edulis (Khat), a stimulant narcotic used in the Middle East and parts of Africa. Isocelorbicol, although one of the more structurally simple members of this group of natural products, still presents synthetic difficulties, in large part due to the presence of six axial substituents appended to a decahydronaphthalene skelton.; Epoxidation of 9-keto-(alpha)-agarofuran followed by rearrangement to allylic alcohol and diimide reduction generated the correct stereochemistry at C-4. Regioselective dehydration of this axial alcohol afforded the desired enone, which afforded the 9(beta)-ol on reduction with lithium aluminum hydride. The hydroxyl group was protected as the benzoate ester, which was subjected to the sequence, epoxidation, treatment with phenylselenide and oxidative elimination to give, the expected allylic alcohol. Osmylation of this allylic alcohol gave exclusively the desired 1(alpha), 2(alpha), 3(beta)-triol. Protection of the 1(alpha), 2(alpha)-diol unit as the acetonide, followed by Barton deoxygenation and deprotection gave the natural product.; This dissertation describes a highly regio and stereo-selective synthesis of ((+OR-)) Isocelorbicol in 15 steps (3.2%) from 9-keto-(alpha)-agarofuran. |
