Synthetic studies towards dictyoxetane and the dolabellanes : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Chemistry, Massey University, New Zealand

Abstract

Dictyoxetane (1) has been isolated from Dictyota dichotoma, a brown alga found in the Indian Ocean. It has an unusual pentacyclic structure which has not yet been synthesised. It is a diterpene which is closely related to the dolabellanes, an important class of bioactive compounds. A stereoselective synthesis of the linearly fused cyclohept[f]indene system is described. Selective epoxidation of cycle-octadiene (142), followed by hydrolysis to the diol (143) and oxidative cleavage allowed preparation of the dialdehyde (141) on large scale. Treatment of this with potassium carbonate causes an intramolecular aldol reaction to form cycloheptadiene- carboxaldehyde (140). An E- selective Wittig reaction is performed with 4- carboxybutyl-triphenylphosphium bromide, to produce the acid (139). This is subsequently converted to the vinyl ketone (138) followed by an intramolecular Diels Alder reaction to produce the desired cyclohept[f]indene (137a). Utilisation of a Z- selective Wittig reaction produced methyl ester (145z). Conversion to cyclohept[f]indene occurred via an intramolecular Diels-Alder of the subsequent vinyl ketone (138z). Conversion of acid (139) to the methyl ester (145) followed by an intermolecular Diels Alder gave the endo- product. Subsequent attempts to cyclise this to the cyclohept[f]indene via an intramolecular Claisen reaction to give the third isomer were unsuccessful. Cyclohept[f]indene is the backbone for dictyoxetane and can be efficiently synthesised in eight steps from 1,5-cyclo-octadiene (142) in a diastereoselective synthesis. This route allows for further modification of functionality to the linearly fused ring system and paves the way for further synthetic studies towards the dolabellanes.