Issue 18, 2017

Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

Abstract

Post-translational lipid modifications farnesylation and geranylgeranylation of proteins (protein prenylation) have been identified to mediate critical events in cancer, cardiovascular disorders, malaria and bone disorders like osteoporosis. To date eight compounds are commercialized for the treatment of bone disorders, and there are considerable efforts to develop selective small molecules that inhibit protein prenylation. This review summarizes the approaches currently employed to synthesize new inhibitors of isoprenoid biosynthesis. Bisphosphonates are mainly prepared through reaction of carboxylic acids with phosphorus reagents, Michael addition to tetraethylvinylidenebisphosphonate and alkylation of tetralkylmethyl bisphosphonate. Approaches to non-bisphosphonate derivatives include a variety of methodologies depending on the structure of the target compound.

Graphical abstract: Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

Article information

Article type
Review Article
Submitted
16 Dec 2016
Accepted
07 Feb 2017
First published
10 Feb 2017
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2017,7, 10947-10967

Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

P. Merino, L. Maiuolo, I. Delso, V. Algieri, A. De Nino and T. Tejero, RSC Adv., 2017, 7, 10947 DOI: 10.1039/C6RA28316K

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