STUDIES DIRECTED TOWARD THE TOTAL SYNTHESIS OF JOLKINOL D (SEVEN-RING, CLOSURE, CHIRAL, DITERPENE)
Abstract
This dissertation describes the attempts towards the total synthesis of jolkinol D, a diterpene belonging to the Lathyrane family. The target molecule is characterized by a tricyclic 10.3.0.0. pentadecane ring system containing two trans double bonds at the 3 and 10 positions. The synthetic scheme involves four major objectives: (1) the closure of the 3-membered ring via a reductive cyclization process, (2) addition of a 6-ring allyl nitrile to a 5-ring vinyl sulfone, (3) closure of a 7-membered ring, (4) and finally an enolate assisted fragmentation for the synthesis of the 11-membered ring. The closure of the 3-membered ring was accomplished via a Mg 0 mediated reductive cyclization of a dienyl nitrile, which was synthesized efficiently from (S)-(-)-Perillaldehyde. The resulting allyl nitrile was successfully added to the prerequisite vinyl sulfone, prepared earlier by Fuchs and coworkers. Application of previous vinyl sulfone methodology allowed for the preparation of the (alpha)-substituted cyclic enone. Nucleophilic 1,2-addition to this enone was successful however, only after the protection of the alpha-nitrile position with a thiomethyl group. An efficient method was developed to remove this thiomethyl moiety at a later stage in the synthesis, since all the known methods failed to accomplish the deprotection without opening of the 3-membered ring. The next major criteria required for the synthesis was the formation of the 7-membered ring. This required a change of strategy but was finally successful via the use of known chemistry developed by Trost.
Degree
Ph.D.
Subject Area
Organic chemistry
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.