Serendipitous discovery of a regioselective synthesis of novel benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters, 3-benzoyloxy-3-(phenylsulfanyl)-β-lactams and their antimicrobial evaluation

Abstract

The regioselective benzoyloxylation process involves stirring a mixture of phenyl/benzyl-sulfanyl/selenylethanoate 1a-c with appropriate oxidant [benzoyl peroxide (BPO) 2a/ m-chloroperbenzoic acid (m-CPBA) 2b /bis(p-methoxybenzoyl peroxide) (BPM-BPO) 2c] under catalysis of hydrated copper acetate in toluene at 60 °C/RT. Regioselective C–H functionalization of esters 1a-c leads to benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters 3a-g in good to excellent yields (80–95%). Variably substituted trans-3-phenylsulfanyl-β-lactams 4 employed for C3-H functionalization with BPO 2a generates diastereoisomeric mixture of trans- and cis-3-benzoyloxy-3-(phenylsulfanyl)-β-lactams 5 and 6 as major and minor isomers after efficient column chromatographic purification. The structural confirmation was done using IR, ¹H NMR, ¹³C NMR, DEPT-90 NMR spectroscopic analysis and CHNS elemental analysis. In vitro antibacterial and antifungal evaluations on bisesters suggest benzylselenyl-bisester 3c as potent antimicrobial agent. Out of trans- and cis-3-benzoyloxy-β-lactams 5a and 6a, the trans isomer 5a was active against all microbial strains whereas the cis isomer 6a was completely inactive.

GRAPHICAL ABSTRACT

KEYWORDS:

• Benzoyloxylation
• benzoates
• benzoyloxy
• bisesters
• β-lactams

Acknowledgements

The authors are thankful to Department of Science and Technology (DST), New Delhi, Government of India, UGC-BSR and Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, Chandigarh, India.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Department of Science and Technology (DST), New Delhi, India [grant number SR/FT/CS-037/2010] and University Grants Commission, New Delhi, India[grant number F.25.1/2013-14(BSR)/5-91/2007(BSR)].