127791-77-9Relevant articles and documents
Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors
Binder, Randall J.,Hatfield, M. Jason,Chi, Liying,Potter, Philip M.
, p. 79 - 89 (2018/03/06)
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 consequence, we have synthesized highly potent inhibitors of these enzymes (Ki 15 nM), that maintain the core tanshinone scaffold. Hence, we have developed a facile and reproducible method for the synthesis of abietane analogues that have resulted in a panel of miltirone derivatives that will be useful tool compounds to assess carboxylesterase biology.
Synthesis of Miltirone by an Ultrasound-Promoted Cycloaddition
Lee, Junning,Mei, Hsiao Shan,Snyder, John K.
, p. 5013 - 5016 (2007/10/02)
The ultrasound-promoted cycloaddition of 3-isopropyl-o-benzoquinone, generated by the in situ silver oxide oxidation of the corresponding catechol, with 6,6-dimethyl-1-vinylcyclohexene has led to the synthesis of miltirone.
