Efforts Toward an Oxa-conjugate Addition Based Approach to (+)-Neopeltolide Synthesis

• Main Author: Hari, Taylor P.A.
• Other Authors: Boddy, Christopher
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2012
• Subjects: neopeltolide; synthesis; review; natural product; polyketide
• Online Access: http://hdl.handle.net/10393/23125; http://dx.doi.org/10.20381/ruor-5293

(+)-Neopeltolide is a highly potent marine polyketide natural product with activity against multiple cancer cell lines in vitro. The nanomolar range of antifungal and anticancer cytotoxicity in this tetrahydropyran (THP)-containing polyketide, combined with its limited natural supply, has led to several syntheses. In this study, the feasibility of an oxa-Michael conjugate addition route to cis-2,6-THP rings is examined through the efforts toward a total synthesis of the macrocyclic core of (+)-neopeltolide using a highly convergent route. This study is based on the successful preliminary results with a simple 14-member ring model system and the synthesis of the key aldehyde intermediate shown below. The highlighted transformation of this synthesis will be a transannular oxa-conjugate addition to generate the cis-2,6-tetrahydropyran ring system. This route also highlights a highly convergent Wittig coupling to generate the full carbon framework of (+)-neopeltolide. One of the key goals of this project is to compare this synthesis with a chemo-enzymatic total synthesis that relies on chemistry catalyzed by polyketide synthase enzymes in the late stage of the synthesis.