TOTAL SYNTHESIS OF (+/-)-MYROCIN-C

A stereoselective total synthesis of racemic myrocin C (1) has been achieved. Initial investigations produced cyclopropane-containing AB sector 22 via intramolecular ester-tethered Diels-Alder reaction of quinone 14 followed by internal alkylation of bromide 19. Although the natural product was not to be obtained through this route, the information garnered from this impetus provided the basis for a strategically improved and ultimately successful synthesis of 1. Thus, intermolecular Diels-Alder reaction of p-benzoquinone with cyclic diene 39 gave endo cycloadduct 41 which could be elaborated to cyclopropane precursors 52 and 99. While a plethora of intramolecular alkylation reactions of derivatives of 52 failed to afford cyclopropane-containing products, a novel organolithium-induced cyclization reaction of 99 did indeed provide key compound 96 via postulated intermediate 100. The resultant functionality in 96 paved the way for a directed intramolecular Diels-Alder annulation of the C-ring and concomitant introduction of the remote quaternary C13 stereocenter (cf. 96 --> 107 --> 108). The tertiary hydroxyl group at C9 was then introduced via epoxidation of 119 followed by overall eliminative ring-opening (123 --> 125 --> 5). The incorporation of the C6 tertiary hydroxyl group was accomplished via oxidation of the enolate derived from 6-desoxymyrocin C (5), yielding racemic 1. Studies on the bioactivation process of 5 and 1 led to support for a hypothesis which emphasized the importance of the C6 hydroxyl group in facilitating cyclopropane-ring-opening possibly through the intermediacy of quinone homomethide 134.