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DOI: 10.1055/s-0036-1596745
Harnessing the main event of drimentines biosynthesis: bio-inspired synthesis and biological evaluation of Δ8'-isodrimentine A and related compounds
Publication History
Publication Date:
14 December 2016 (online)
Drimentines are a family of alkaloids biosynthetically originating from the condensation of a sesquiterpene unit onto a tryptophan-containing cyclic dipeptide [1]. These alkaloids feature a fused diketopiperazino-pyrroloindoline core. Their scaffold is likely to arise from an indol-dearomatization followed by the intramolecular trapping of an indolenine intermediate. The aim of the study was to exploit this biosynthetic hypothesis to develop a straightforward assembly of the drimentine A core. This concise synthetic sequence is described herein. Our dual strategy involves the alkylation of a tryptophane-containing cyclodipeptide by a drimane-type-decaline or a linear C15 unit. In both approaches, the starting cyclopeptide was obtained by classical peptidic couplings. The drimane-type-decaline was prepared from sclareolide while the fully biomimetic approach was also evaluated with the synthesis of a farnesyl-substituted pyrrolo-indoline diketopiperazine. That farnesylated derivative is corresponding to a biosynthetic precursor of drimentines A and D. The envisioned dearomatization-trapping sequence has been successfully realized validating the synthetic rational and furnishing biosynthetic clues. Hence, very close analogs of the natural substances, such as Δ8'-isodrimentine A, have been obtained and biologically evaluated [2].
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Keywords: Drimentines, biomimetic synthesis, alkaloids, dearomatization.
References:
[1] Che Q, Zhu T, Qi X, Màndi A, Kurtàn T, Mo X, Li J, Gu Q, Li D. Hybrid isoprenoids from a reeds rhizosphere soil derived actinomycete streptomyces sp. CHQ-64. Org Lett 2012; 14: 3438 – 3441
[2] Skiredj A, Beniddir M A, Evanno L, Poupon E. Mimicking the main event of drimentines biosynthesis: synthesis of Δ8'-isodrimentine A and related compounds, biological evaluation. Eur J Org Chem Eur. doi: 10.1002/ejoc.201600444