Total synthesis of the proposed structure of nhatrangin A and analogs

Author(s)

Ellen Christine Polo

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2015-04-30

Examining board members

Luiz Carlos Dias; Adriano Lisboa Monteiro; Giuliano Cesar Clososki; Carlos Roque Duarte Correia; José Augusto Rosário Rodrigues

• Advisor: Luiz Carlos Dias

Abstract

The nhatrangin A was isolated in 2010 by Orjala and co-workers, from a Vietnamese collection of marine cyanobacterium Lyngbya majuscula. This polyketide containing six stereogenic centers and its structure was assigned based on spectrometric and spectroscopic methods including 1D and 2D NMR experiments. The aim of this work was to investigate the convergent and flexible synthetic route for obtaining this natural product and check the structural assignment proposed by the authors of isolation. The proposed structure of nhatrangin A was synthesized in 19 steps, considering the longest linear route, and overall yield of 6.7%. The key steps involved aldol reaction, Corey-Fuchs reaction, lithium-mediated coupling between alkyne and Weinreb amide, Noyori stereoselective reduction and Yamaguchi esterification. In addition, we synthesized six diastereoisomers of the proposed structure for the natural product, using the same synthetic strategy employed in the synthesis of the proposed structure of nhatrangin A, however none of these isomers correspond to the natural product (AU)

• FAPESP's process: 11/06722-2 - Total synthesis of nhatrangins A and B
• Grantee: Ellen Christine Polo
• Support Opportunities: Scholarships in Brazil - Doctorate