Enantioselective Total Synthesis and Structural Revision of Dysiherbol A

Abstract

A 12‐step total synthesis of the natural product dysiherbol A, a strongly anti‐inflammatory and anti‐tumor avarane meroterpene isolated from the marine sponge Dysidea sp., was elaborated. As key steps, the synthesis features an enantioselective Cu‐catalyzed 1,4‐addition/enolate‐trapping opening move, an Au‐catalyzed double cyclization to build up the tetracyclic core‐carbon skeleton, and a late installation of the C5‐bridgehead methyl group via proton‐induced cyclopropane opening associated with spontaneous cyclic ether formation. The obtained pentacyclic compound (corresponding to an anhydride of the originally suggested structure for dysiherbol A) showed identical spectroscopic data as the natural product, but an opposite molecular rotation. CD‐spectroscopic measurements finally confirmed that both the constitution and the absolute configuration of the originally proposed structure of (+)‐dysiherbol A need to be revised.

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products

“…8). 55 Plakinidone (36) from the Caribbean sponge Plakortis angulospiculatus, was originally reported as the rst naturally occurring six-membered peroxylactone (Fig. 8) and showed mild antimicrobial activity.…”

Recent Achievements in Total Synthesis for Integral Structural Revisions of Marine Natural Products

“…However, it was later found that the hydroxyl group at the C-4 position of the A ring and the hydroxyl group at the C-20 of the D ring (see Table 1 , entry 3) were fused to form a pentacyclic skeleton containing an ether bond. Subsequently, the Schmalz [ 17 ] and Liu [ 18 , 19 ] groups individually synthesized the confirmed structure of dysiherbol A for the first time, although different synthetic routes were employed.…”

Assembling Complex Structures through Cascade and Cycloaddition Processes via Non-Acceptor Gold or Rhodium Carbenes

“…52 In this manner, we synthesized a variety of highly substituted indenes by reaction of 7-aryl cycloheptatrienes 47 and 1,2-disubstituted allenes 52, using a cationic gold(I) complex as catalyst (Scheme 25, top). This strategy allowed the preparation of indene intermediate 53e, which after elaboration through 5-6 more steps, led to the construction of the carbon skeletons of both the cycloaurenones and the dysiherbols, 53 two families of natural products featuring a cis-or trans-decalin core, respectively (Scheme 25, bottom). In contrast, we found that if 7-styryl cycloheptatrienes 54 are used as carbene precursors, the same allenes react to give cyclopentadienes 55 (Scheme 26).…”