Scalable, Divergent Synthesis of Meroterpenoids via “Borono-sclareolide”

Abstract

A scalable, divergent synthesis of bioactive meroterpenoids has been developed. A key component of this work is the invention of "borono-sclareolide", a terpenyl radical precursor that enables gram-scale preparation of (+)-chromazonarol. Subsequent synthetic operations on this key intermediate permit rapid access to a variety of related meroterpenoids, many of which possess important biological activity.

Scalable, Electrochemical Oxidation of Unactivated C–H Bonds

“…19 To this end, the ability to procure ample amounts of 2-oxo-sclareolide ( 2 , Figure 2A, inset photograph) via electrochemical C–H oxidation affords the unique opportunity to examine the 2-oxo analogues of these bioactive terpenoids. In our previous strategy toward meroterpenoids, sclareolide was converted into its borono analogue, which served as a “terpenyl radical” progenitor.…”

A Concise Route to the Strongylophorines

“…[3, 4] Meroterpenoids are a terpenoid subclass resulting from hybrid biosynthetic pathways that fuse terpene substructures with polyketide or alkaloid components. [5,6] Our laboratory takes an interest in natural products with challenging structural features and unclarified biological activities.[7] The strongylophorines (STRs, Figure S1 in the Supporting Information) are a family of meroditerpenoids initially isolated from the marine sponges Strongylophora durissima and Petrosia cortica, [8, 9b] with members displaying diverse biological activity, including neuroprotective effects (STR-8), [9a] anti-invasive activity (STR-26), [9b-d] and inhibitory activity against HIF-1 (STR-2, 3, and 8).[9e] To date, no syntheses of any of the strongylophorines have been reported. Structurally, STR-2 (1, Figure 1) occupies a central position within the STR-family since this compound provides a favorable point of diversification and contains the synthetically challenging bicyclic d-lactone functionality at the AÀB ring junction found in most of the bioactive STRs.…”

Total Synthesis of Indotertine A and Drimentines A, F, and G

“…Sclareolide (11) was converted into iodoformate 12 using the two-step method developed by Baran et al (DIBAL-H reduction followed by Suµrez cleavage). [18] Compound 11 was then further hydrolyzed to give alcohol 13 (78 % yield from 11). Treatment of 13 with SOCl 2 /Et 3 N furnished exocyclic olefin 14 in 86 % yield, the C=C bond of which was cleaved by ozonolysis.…”