Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors.

ABSTRACT: Recently, a series of selective human carboxylesterase inhibitors have been identified based upon the tanshinones, with biologically active molecules containing a 1,2-dione group as part of a naphthoquinone core. Unfortunately, the synthesis of such compounds is complex. Here we describe a novel method for the generation of 1,2-dione containing diterpenoids using a unified approach, by which boronic acids are joined to vinyl bromo-cyclohexene derivatives via Suzuki coupling, followed by electrocyclization and oxidation to the o-phenanthroquinones. This has allowed the construction of a panel of miltirone analogues containing an array of substituents (methyl, isopropyl, fluorine, methoxy) which have been used to develop preliminary SAR with the two human carboxylesterase isoforms. As a cons

SUBMITTER: Binder RJ 

PROVIDER: S-EPMC5863762 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature