Total synthesis of meloscine by a [2+2]-photocycloaddition/ring-expansion route.
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.
Selig
Philipp
P
Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
Herdtweck
Eberhardt
E
Bach
Thorsten
T
D002384:Catalysis; D003500:Cyclization; D003503:Cyclobutanes / Q000737:chemistry; D010777:Photochemistry; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D003503:Cyclobutanes; D011083:Polycyclic Compounds; D011804:Quinolines; C530682:meloscine