616206-08-7Relevant academic research and scientific papers
A short and concise asymmetric synthesis of hamigeran B
Trost, Barry M.,Pissot-Soldermann, Carole,Chen, Irwin
, p. 951 - 959 (2005)
The interesting biological properties of the hamigerans wherein hamigeran B is a potent antiviral agent with low cytotoxicity to host cells make these deceptively simple looking structures challenging synthetic targets. A strategy to hamigeran B evolved wherein the three contiguous stereocenters are established ultimately from a Pd catalyzed asymmetric allylic alkylation (AAA). The latter involves an asymmetric allylation of a non-stabilized ketone enolate in 77% yield and 93% ee. By using this process, (S)-5-allyl-2-isopropyl-5- methyl-1-trifluoromethanesulfonyloxycyclopentene becomes available in four steps from 2-methylcyclopentanone. Introduction of the aryl unit by cross-coupling proceeded intermolecularly but failed intramolecularly. On the other hand, reductive removal of the triflate permitted a Heck reaction to effect intramolecular introduction of the aryl ring. The unusual conformational properties of this molecular architecture are revealed by the regioselectivity of the β-hydrogen elimination in the Heck reaction and the diastereoselectivity of the reduction establishing the stereochemistry of the carbon bearing the isopropyl group. The successful route consists of 15 steps from 2-methylcyclopentanone and dimethylorcinol illustrating the efficiency of the route based upon the Pd AAA.
Enantiospecific total synthesis of 6-epi-(-)-hamigeran B. Intramolecular Heck reaction in a sterically constrained environment
Mehta, Goverdhan,Shinde, Harish M.
, p. 7049 - 7053 (2007/10/03)
An enantiospecific approach, emanating from the abundantly available chiron R-(+)-limonene, to the biologically potent, novel marine natural products, the hamigerans has been developed in which an intramolecular Heck coupling between aryl triflates and an alkene serves as the pivotal step. Following this strategy, a synthesis of (-)-6-epi-hamigeran B has been accomplished.
