Synthesis of Ring-Contracted Erythromycin A Derivatives via Microwave-Assisted Intramolecular Transesterification

Kai Bao,Chuanliang Zhang,Weige Zhang,Yingwei Qu,Xiang Zhao,Maosheng Cheng,Lan Wu,Liang Tian

doi:10.3390/12092123

Abstract

The synthesis of ring-contracted derivatives of erythromycin A via intramolecular transesterification under microwave irradiation of 8,9-anhydroerythromycin A 6,9-hemiketal and its derivatives is described. It was found that microwave irradiation could significantly improve the yields and shorten the reaction times under either solvent-containing (method A) or solvent-free (method B) conditions.

Highlights

Erythromycin, a typical macrolide antibiotic, was the first employed clinically and it has provided new opportunities for the discovery of potential therapeutic agents [1]
In 1987, Kibwage et al observed that 8,9-anhydroerythromycin A 6,9-hemiketal (1a) and its intramolecular transesterification product 2a could be obtained in ca. 18 and 71 % yields, respectively, after chromatographic purification of the mixture of products formed when erythromycin A was heated in a 3:1 mixture of pyridine and acetic acid at 70°C for 24 h [4]
Compound 1a, which was obtained from erythromycin A under acid treatment [9], could be transformed into 2a within a few minutes under microwave irradiation by catalysis with potassium carbonate and tetra-n-butylammonium bromide (TBAB) in DMF

Summary

Introduction

Erythromycin, a typical macrolide antibiotic, was the first employed clinically and it has provided new opportunities for the discovery of potential therapeutic agents [1]. Numerous clinical studies have confirmed that erythromycin and its derivatives have additional antiinflammatory and prokinetic activity [2,3]. The ring-contracted erythromycin derivative 2a came to our attention on the basis of its anti-inflammatory activity, and was selected as one of our target compounds. 18 and 71 % yields, respectively, after chromatographic purification of the mixture of products formed when erythromycin A was heated in a 3:1 mixture of pyridine and acetic acid at 70°C for 24 h [4]. And almost simultaneously Kirst and co-workers reported that the translactonization of 1a catalyzed by potassium carbonate in refluxing methanol gave compound 2a in 54% yield after 90 min [5]

Methods

Results

Conclusion