Total Synthesis of (−)‐Nakadomarin A. Issue 13 (29th February 2016)

• Record Type: Journal Article
• Authors: Clark, J. Stephen; Xu, Chao
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 13(2016)
• Page Start: 4332
• Page End: 4335
• Publication Date: 2016-02-29
• Subjects: alkaloids -- natural products -- Overman rearrangement -- ring-closing metathesis -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201600990
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A highly efficient 12‐step synthesis of the marine alkaloid (−)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (−)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids. Abstract : The later the better : A highly efficient 12‐step synthesis of (−)‐nakadomarin A is reported. The key tetracyclic ketone intermediate was constructed from a simple enyne in seven steps. As the furan is introduced at a later synthetic stage, this intermediate may have potential in the syntheses of related marine alkaloids such as manzamine A and ircinal A.