Oxidative Cyclization Reactions of Trienes and Dienynes: Total Synthesis of Membrarollin

• Published in: Journal of organic chemistry Vol. 74; no. 3; pp. 981 - 988
• Main Authors: Morris, Claire L, Hu, Yulai, Head, Geoff D, Brown, Lynda J, Whittingham, William G, Brown, Richard C. D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 06-02-2009
• Subjects: Acetogenins - chemical synthesis; Alkynes - chemistry; Annonaceae - chemistry; Chemistry; Cyclization; Exact sciences and technology; Furans - chemical synthesis; Furans - chemistry; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Oxidation-Reduction; Polyenes - chemistry; Preparations and properties; Acetylenic compound; Epimer; Furan derivatives; Selectivity; Metal; Stereochemistry; Oxygen heterocycle; Tetrahydrofurane; Stereoselectivity; Alkene; Hydroxyl group; Oxidation; Acetogenin; Chemical synthesis; Protection; Erythro stereoisomer; Permanganates; Diol; Trienic compound; Regioselectivity; Dienic compound; Ketone; Total synthesis; Enynic compound; Polyketide; Cyclization; Absolute configuration; Threo stereoisomer; Ethylenic compound; Alkyne
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo802012a

Trienes and dienynes containing one electron-deficient double bond were shown to undergo regio- and stereoselective oxidative cyclization in the presence of permanganate ion to afford 2,5-bis-hydroxyalkyltetrahydrofurans (THF diols). The THF diols produced retained either alkene or alkyne functionalities, which provided convenient handles for the metal oxo-mediated introduction of an adjacent THF ring with overall control of relative and absolute stereochemistry. Adjacent bis-THFs possessing threo-cis-threo-trans-erythro, threo-cis-threo-trans-threo, threo-cis-threo-cis-erythro, threo-cis-erythro-cis-threo, or threo-cis-erythro-trans-threo relationships were synthesized by appropriate selection of alkene geometry and methodology for the closure of the second ring. The threo-cis-threo-cis-erythro stereochemical arrangement is embodied within the bis-THF core units of a number of Annonaceous acetogenins including membrarollin, while trilobacin has a threo-cis-erythro-trans-threo configured core. As an application of the selective oxidative cyclization approach, a total synthesis of membrarollin was completed in 17 linear steps from dodecyne. The C21,C22 double epimer of membrarollin was also synthesized in 15 linear steps and without recourse to the use of hydroxyl group protection.