New acylides: synthesis of 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives

Deepa Pandey,Wahajul Haq,Seturam B Katti

doi:10.3762/bjoc.4.14

Abstract

In search of new erythromycin derivatives 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives have been synthesized. The 3-hydroxy group was derivatised to a primary amine and subsequently the thiazolidinone nucleus was generated at the amino functionality through DCC mediated one-pot three-component reaction in good yields.

Highlights

Second-generation macrolides, namely clarithromycin (CAM), roxithromycin and azithromycin (Figure 1), provide good coverage against all key respiratory pathogens [1,2,3,4]
We have developed a synthesis where the 3-OH group of 1 was functionalized to an amino group using the γ-aminobutyryl spacer and subsequently a variety of thiazolidinone moieties were generated at the amino group
We have explored other spacers for generating the amino group e.g. Z-Gly, Z-Ala and Z-β-Ala etc. but due to severe steric hindrance the formation of the thiazolidinone was not successful

Summary

Introduction

Second-generation macrolides, namely clarithromycin (CAM), roxithromycin and azithromycin (Figure 1), provide good coverage against all key respiratory pathogens [1,2,3,4]. Structural modifications in the macrolides have been the most important approach for the development of novel antibacterials active against resistant strains of bacteria. Development of new strategies for the synthesis of novel structures is of prime importance in the area of macrolides. The thiazolidin4-ones can be generated under very mild conditions using the DCC mediated one-pot synthesis reported by us [12].

Results

Conclusion