Englerin, a naturally occurring sesquiterpene diester: Isolation, synthesis and biological relevance

Abstract

The englerins are oxo-bridged guaiane sesquiterpene natural products, isolated from the stem bark of Phyllanthus engleri, which exhibit low nanomolar anticancer properties against renal cell carcinoma. Englerin A, the more active of the two family members, has thus become a highly attractive target for total synthesis, particularly in terms of scalability and the potential to generate libraries of englerin analogues. This review offers a comprehensive coverage of total and formal syntheses of englerins A and B, along with synthetic analogues that possess useful biological activities. Numerous total syntheses have been reported, underlining the interest and importance of this natural product as a medicinal chemistry target. Common strategies include the use of ring-closing metathesis to form the seven-membered carbocyclic core, gold(I)-catalyzed [2 ​+ ​2+2] cyclization, reductive Mizoroki–Heck cyclization, regio and diastereoselective (4 ​+ ​3) cycloaddition, Nazarov cyclization and C–H sulfamination, and epoxynitrile cyclization.