Toward the Total Synthesis of Spirastrellolide A. Part 1: Strategic Considerations and Preparation of the Southern Domain

Abstract

North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. The southern hemisphere (C1–C25) and the northern hemisphere (including the chlorinated [5,6,6]-bis-spiroacetal entity and the lateral C42–C47 chain) are prepared by concise and efficient routes. Consequently, the entire carbon framework of this potent phosphatase inhibitor, which contains 21 chiral centers, is prepared in an optically active form, and an important step toward structure determination by total synthesis is achieved.