Total synthesis of meloscine by a [2+2]-photocycloaddition/ring-expansion route

Philipp Selig, Eberhardt Herdtweck, Thorsten Bach

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

The unusual monoterpenoid indole alkaloid meloscine was synthesized starting from a protected aminoethylquinolone in 15 steps and an overall yield of 9%, employing a [2+2]-photocycloaddition as the stereochemistry defining key step. After the initial plan of a Wagner-Meerwein type rearrangement of a [4.2.0]- into a [3.3.0]-bicyclic substructure could not be realized, the required ring enlargement of a cyclobutane was eventually achieved by a retro-benzilic acid rearrangement. Generation of the central pyrrolidine ring was possible by a three-step reductive amination domino sequence. The final ring was built up by a ring-closing metathesis after the last quaternary stereocenter had been constructed by a Johnson-Claisen rearrangement. The synthesis was concluded by a selenylation-elimination sequence to build up the exocyclic vinyl group of meloscine. Using our methodology for enantioselective [2+2]-photocycloaddition mediated by a chiral complexation agent, the experimentally very simple synthesis could be performed in an enantioselective fashion (7% overall yield). The enantioselective synthesis of (+)-meloscine represents the first example of a natural product synthesis employing an enantioselective [2+2]-photocycloaddition as its key step, and illustrates nicely the synthetic potential of photochemical transformations for the construction of complex heterocyclic structures.

Original languageEnglish
Pages (from-to)3509-3525
Number of pages17
JournalChemistry - A European Journal
Volume15
Issue number14
DOIs
StatePublished - 23 Mar 2009

Keywords

  • Asymmetric synthesis
  • Natural products
  • Photochemistry
  • Rearrangement
  • Total synthesis

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