Syntheses of Gliocladin C and Related Alkaloids

Abstract

A unique approach to gliocladin C and related alkaloids was developed that features an unprecedented nucleophilic addition of a diketopiperazine to an isatin derivative followed by a Friedel-Crafts alkylation of the resultant tertiary alcohol with indole to set the key quaternary center. Chemoselective oxindole reduction and cyclization delivered a pivotal hexahydropyrrolo[2,3-b]indole diketopiperazine intermediate that was readily converted into (±)-gliocladin C, (±)-T988C, and (±)-gliocladine C, culminating in the shortest approach to these alkaloids reported to date.

Enantioselective synthesis of mixed 3,3′-bisindoles via a phosphine-catalyzed umpolung γ-addition of 3′-indolyl-3-oxindoles to allenoates

“…Compound 7 then underwent a three-component reaction with benzoyl hydrazine and TMSCN to afford a-aminonitirile 8 in a highly diastereoselective manner. Finally, hydrolysis and reductive cyclization furnished compound 9, the core structure of Gliocladin C and its related nature product family [81][82][83][84][85][86][87] (Scheme 5).…”

Arenesulfonyl indole: new precursor for diversification of C-3 functionalized indoles

“…gliocladin C, which contains a 3-substituted-3indolyloxindole, is a marine alkaloid. 31 Bisai and co-workers 32 reported the thiourea I catalysed addition of malonates 26 to 3sulfonyl-3 0 -indolyl-2-oxindoles (25) to obtain C-3 substituted indole derivatives 27 containing an all carbon quaternary stereogenic centre in 67-86% yields with 84-92% ee (Scheme 8). The author also mentioned the role of stronger p-p interactions behind the enhanced enantioselectivity.…”

Divergent Strategy in Natural Product Total Synthesis

“…In 2017, the Martin group reported a unique approach to formal synthesis of the other two members of ETP alkaloids, T988C ( 145 ) and gliocladine C ( 146 ), and total synthesis of a related hexahydropyrrolo­[2,3- b ]­indole diketopiperazine (DKP) alkaloid gliocladin C ( 144 ) from the common intermediate 141 (Scheme ). The synthesis of 141 features an unprecedented nucleophilic addition of a diketopiperazine to N -allyl isatin and a Friedel–Crafts alkylation of the resulting tertiary alcohol with indole to install the key quaternary center. Diketopiperazine 137 was prepared from oxazolidine 135 over four steps.…”