A straightforward total synthesis of (-)-chaetominine

Beatrice Malgesini, Barbara Forte, Daniela Borghi, Francesca Quartieri, Cesare Gennari, Gianluca Papeo (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

A total synthesis of the tripeptide alkaloid (-)-chaetominine (1) was achieved in 9.3% overall yield starting from commercially available Dtryptophan methyl ester, based on a short and straightforward (nine steps) sequence. The early stage introduction (first step) of the quinazolinone moiety and the late stage introduction (penultimate step) of the hydroxy group allowed a synthetic strategy devoid of protective groups. The key step of the process is the a-c tricyclic ring con-struction via an unprecedented NCSmediated N-acyl cyclization on an indole ring to give tetrahydro-1H-pyrido[2,3-b]indole 11. In the penultimate step, oxidation of the tetracyclic intermediate 14 with oxaziridine 15 gave only one of the four possible diastereoisomers, the cis-diastereoisomer 16 resulting from the attack of the oxaziridine to the double bond face opposite to the c-d ring substituents. In the last step, the complete stereocontrol of the Et3SiH/TFA reduction of compound 16, probably involving a N-acyliminium ion, can be attributed to ring constrain, which forces the b-c ring junction in the more stable cis -orientation. (-)-Chaetominine (1) showed a negligible inhibitory activity on several cancer cell lines.

Original languageEnglish
Pages (from-to)7922-7929
Number of pages8
JournalChemistry - A European Journal
Volume15
Issue number32
Early online date27 Jun 2009
DOIs
Publication statusPublished - 10 Aug 2009

Keywords

  • Alkaloids
  • Amino acids
  • Lactams
  • Natural products
  • Total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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