Studies toward the total synthesis of scytophycin C : sythesis of the C(1)-C(18) fragment

Abstract

The goal of this investigation was to provide a synthetic route to the C(1) - C(18) fragment of scytophysin C 5 which would be amenable to large scale preparation of the target compound. To achieve this goal it would be necessary to circumvent the problems encountered in Grieco and Speakers aforementioned synthesis. These problems were namely the reduction of the nitrile at C(14) in the presence of the C(1) carboxymethyl group and the protecting group manipulations which were necessitated by the alternate homologation strategy which was employed. Synthetic Strategy In order to avoid possible interference resulting from the presence of the C(I) carbomethoxy group during the reduction of the C(14) nitrile it was decided to delay introduction of the C(1) - C(6) portion of the molecule until the last steps of the synthesis. Therefore, it would be necessary to reduce the C(7) aldehyde product of the Ferrier rearrangement and subsequently protect the resultant alcohol. Provided the reduction of the C(14) nitrile was a success the C(15) - C(18) portion of the molecule could then be installed using Roush’s (S,S) diisopropyltartrate-Z-crotylboronate. Finally, the C(1) - C(6) portion of the molecule could be elaborated by deprotection and oxidation of the C(7) alcohol to it’s corresponding aldehyde followed by a vinylogous Muldyama type aldol reaction, Homer-Emmons olefmation, and protection of the C(7) alcohol as its tert-butyldimethylsilyl ether. It was thought that this route, if feasible, would result in a significantly shorter and more efficient synthesis of 5.