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Mimicking the Main Events of the Biosynthesis of Drimentines: Synthesis of Δ8′‐Isodrimentine A and Related Compounds
Author(s) -
Skiredj Adam,
Beniddir Mehdi A.,
Evanno Laurent,
Poupon Erwan
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600444
Subject(s) - chemistry , diketopiperazines , stereochemistry , indole test , biomimetic synthesis , biosynthesis , sesquiterpene , natural product , tryptophan , intramolecular force , combinatorial chemistry , amino acid , biochemistry , enzyme
Drimentines are a family of tetracyclic alkaloids biosynthetically originating from the condensation of sesquiterpene units onto cyclic dipeptides. A straightforward assembly of the fused “pyrroloindoline–diketopiperazine” core of drimentines is described herein and used for the synthesis of Δ 8′ ‐isodrimentine A. The strategy involves a bio‐inspired indole dearomatization of a tryptophan‐containing cyclodipeptide by a drimane‐type decaline followed by the intramolecular trapping of the resulting indolenine intermediate in an uninterrupted reactive sequence. The starting diketopiperazine was prepared by classical peptidic coupling and the drimane‐type decaline from (+)‐sclareolide. A fully biomimetic approach with a linear sesquiterpene unit is also reported and led to farnesylated pyrroloindoline–diketopiperazines, which correspond to the proposed biosynthetic precursors of both drimentines A and D. The end product Δ 8′ ‐isodrimentine A and its congeners were evaluated in vitro for their cytotoxic activities against three human tumor cell lines.