Synthetic Approach to the ABCD Ring System of Anticancer Agent Fredericamycin A via Claisen Rearrangement and Ring-Closing Metathesis as Key Steps

Sambasivarao Kotha; Subba Rao Cheekatla; Ambareen Fatma

doi:10.1021/acsomega.9b01178

Synthetic Approach to the ABCD Ring System of Anticancer Agent Fredericamycin A via Claisen Rearrangement and Ring-Closing Metathesis as Key Steps

ACS Omega. 2019 Oct 14;4(17):17109-17116. doi: 10.1021/acsomega.9b01178. eCollection 2019 Oct 22.

Authors

Sambasivarao Kotha¹, Subba Rao Cheekatla¹, Ambareen Fatma¹

Affiliation

¹ Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400076, India.

Abstract

A new synthetic strategy to the ABCD ring system of the anticancer agent fredericamycin A (NSC-305263) was realized by the Diels-Alder reaction and olefin metathesis as key steps. The tactics developed here for the construction of the ABCD ring system also involve double Claisen rearrangement followed by a retro-Diels-Alder reaction and ring-closing metathesis. The metathesis approach performs a key role in the construction of A and D rings of the ABCD core unit. More importantly, ABCD fragment synthesis was accomplished without the involvement of protecting groups.