Towards the Synthesis of Lyngbyaloside B: Stereoselective Synthesis of the C1-C16 Macrolactone Core Segment

• Published in: European journal of organic chemistry 2013-05, Vol.2013 (15), p.3076-3085
• Main Authors: Yadav, Jhillu S., Haldar, Animesh, Maity, Tapas
• Format: Article
• Language: English
• Subjects: Aldol reactions; Epoxide opening; Macrocycles; Me­tathesis; Natural products
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201300083

A highly stereoselective synthesis of the C1–C16 macrolactone core segment of the cytotoxic macrolide lyngbyaloside B has been achieved. The synthetic strategy involved aldol additions of chlorotitanium enolates of N‐propionyl thiazolidinethiones to achieve non‐Evans as well as Evans syn‐propionate aldol reactions as the key steps to establish four of the seven stereogenic centres present in the macrolactone core (2). The C7 hydroxy group and tertiary hydroxy group at C13 were introduced by using different strategies for the regioselective opening of epoxides generated by Katsuki–Sharpless asymmetric epoxidation. A crucial intermolecular acyl ketene trapping by the tertiary alcohol at C13, and a subsequent ring‐closing metethesis reaction served to unite the northern and southern hemisphere subunits to construct the macrolactone core (2). A highly stereoselective synthesis of the C1–C16 macrolactone core segment of the cytotoxic macrolide lyngbyaloside B has been achieved. Intermolecular acyl ketene trapping by the tertiary alcohol at C13, and a subsequent ring‐closing metathesis reaction served to unite the northern and southern hemisphere subunits to construct the macrolactone core.