Total Synthesis of Myxovirescins, 3 Coupling of the Two Key Fragments and Last Steps to Myxovirescins A1 and M2

✍ Scribed by Maestro, Miguel A. ;Sefkow, Michael ;Seebach, Dieter

• Book ID: 102901984
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 880 KB
• Volume: 1994
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199419940714

✦ Synopsis

Abstract

The last steps of a chiral building‐block approach to the synthesis of myxovirescins A~1~, A~2~ and M~2~ are described. The “northwestern” parts, hydroxy sulfones (see preceding paper), and the “southeastern” parts, hydroxy aldehyde derivatives (first paper in this series), of the target molecules (Scheme 1) are first coupled by a Julia olefination (60–70% yield); the resulting linear intermediates are oxidized (CH~2~OH → CO~2~H) and deprotected for the final Yamaguchi macrolactonization (85–90% yield, Scheme 2). Deprotection by hydrolysis of three different acetal moieties and chromatographic purification gave 20‐mg amounts of synthetic myxovirescins M~2~ and A~1~ (Scheme 3) which were identical in all respects with authentic samples isolated and supplied to us by the team at the Gesellschaft für Biotechnologische Forschung in Braunschweig. – The total syntheses of the macrocyclic antibiotics consist of 62 and 66 steps, and the longest linear sequence of 25 steps was carried out in an overall yield of 2.5 and 0.85% (over 85 and 80% each step), respectively. magnified image