Total Synthesis of Thiostrepton, Part 2: Construction of the Quinaldic Acid Macrocycle and Final Stages of the Synthesis

✍ Scribed by K. C. Nicolaou; Mark Zak; Brian S. Safina; Sang Hyup Lee; Anthony A. Estrada

• Book ID: 101530699
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 428 KB
• Volume: 116
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/ange.200461341

✦ Synopsis

In the preceding Communication in this issue [1] we described the construction of the thiazoline-containing macrocycle 2 as an advanced intermediate toward the total synthesis of thiostrepton (1). Herein we report the construction of suitable dipeptide (8, Scheme 1) and quinaldic acid (22, Scheme 2) fragments, their union with 2, and the final stages of the total synthesis of 1.

Scheme 1 outlines the synthesis of the required dipeptide derivative 8 from 3, a known phenylseleno-substituted derivative of alanine. [2] Thus, 3 was converted into allyl ester 4, which was treated with TFA to effect its conversion into the amino derivative 5. Coupling of amine 5 with Boc-l-alanine