Synlett 2015; 26(16): 2199-2215
DOI: 10.1055/s-0034-1381047
account
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Desmethyl Macrolide Antibiotics

Rodrigo B. Andrade*
  • Temple University, Department of Chemistry, Philadelphia, PA 19122, USA   Email: randrade@temple.edu
Further Information

Publication History

Received: 13 April 2015

Accepted after revision: 09 June 2015

Publication Date:
03 September 2015 (eFirst)

Dedicated to the memory of Dr. Tapas Paul (1976–2012). ‘Chemistry creates its object.’ – Marcelin Berthelot (1860)

Abstract

Macrolide antibiotics occupy a special place in the history of organic chemistry and medicine. This account chronicles the evolution of our approach that ultimately led to the successful total syntheses of four desmethyl (i.e., Me → H) analogues of telithromycin, a semisynthetic derivative of the flagship macrolide antibiotic, erythromycin.

1 Introduction

2 Project Rationale and Retrosynthetic Analysis

3 Lessons Learned from the Total Synthesis of 4,8,10-Tridesmethyl Telithromycin

4 Total Synthesis of 4,10-Didesmethyl Telithromycin

5 Total Synthesis of 4,8-Didesmethyl Telithromycin

6 Total Synthesis of 4-Desmethyl Telithromycin

7 Biological Evaluation of Desmethyl Telithromycin Analogues

8 Concluding Remarks