Studies towards a new approach to total synthesis of the (+)-napalilactone, a halogenated sesquiterpene isolated frm marine source

Author(s)

Bruno Ricardo Vilachã Ferreira

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2005-01-08

Examining board members

Fernando Antonio Santos Coelho; Carlos Kleber Zago de Andrade; Lucia Helena Brito Baptistella

• Advisor: Fernando Antonio Santos Coelho

Abstract

Napalilactone and Pathylactone A are two sesquiterpenoids spirolactones isolated from marine corals. These sesquiterpenes, biogenetically derivable from an aristolene carbon skeleton, show in their structures four contiguous stereocenters and differ only in the nature of heteroatom substituent (Cl versus OH) adjacent to the spirolactone ring junction. As part of a research program directed toward the total synthesis of some marine natural products, we describe in this work a study focused on the development of a straightforward method, which would allow the preparation of an optically active functionalized alkene. This key intermediate could be used for the asymmetric synthesis of both sesquiterpenes. Owing to the high cost of (S)-pulegone, we began this work using (R)-pulegone as a model system. Our aim was to establish a synthetic strategy that later could be surpassed for the synthesis of the sesquiterpenes cited. Based on data previously described from our laboratory for the racemic synthesis of Pathylactone-A, we carried out a sequence of reactions in an attempt to form the functionalized alkene. According to the synthetic route from (R)-(+)-pulegone, the intermediate selenide was prepared in 9 steps with overall yield of 13%. In view of the success in the synthesis of advanced intermediates from (R)-pulegone, this same synthetic sequence could be used for the asymmetric synthesis of (+)-Napalilactone, using as starting material the (S)-(-)-pulegone (AU)