Total synthesis of punctaporonin C by a regio- and stereoselective [2+2]-photocycloaddition.
The unique sesquiterpene punctaporonin C was synthesized starting from commercially available 7-tert-butoxynorbornadiene in a linear sequence of 29 steps and with an overall yield of 0.65%. Key step of the synthesis was an intramolecular [2+2]-photocycloaddition, in which the two vinylic double bonds in a 1,3-divinyl-2-cyclopentyl tetronate were differentiated by reaction with the photoexcited tetronate. The reaction gave regio- and diastereoselective access to the tricyclic core skeleton of punctaporonin C in 63% yield. Additional studies related to the tetronate [2+2]-photocycloaddition revealed that even diastereotopic vinylic double bonds in a 1,3-divinyl-2-cyclopentyl tetronate can be differentiated (d.r. up to 78:22). In the further course of the total synthesis the complete tetracyclic oxatetracyclo[6.3.2.0(1, 4).0(5, 12)]tridecane skeleton of punctaporonin C was established by an intramolecular aldol reaction, closing a seven-membered oxepane ring. The nucleophilic methyl ketone employed in this step was generated by Wacker oxidation of the vinylic double bond, which was not involved in the [2+2]-photocycloaddition. Several reactions employed in the synthetic sequence required adaptation to the rigid skeleton of punctaporonin C, for example, the reduction of a mesylate, the alkylation of a cyclobutane carboxylate, or the methyl addition to a prostereogenic carbonyl group.
Fleck
Martin
M
Lehrstuhl für Organische Chemie 1, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Bach
Thorsten
T
D000478:Alkylation; D001688:Biological Products / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010777:Photochemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D001688:Biological Products; D012717:Sesquiterpenes; C531406:punctaporonin C