46 Prostagrandin誘導体の合成 : 12,15-ethanoprostaglandinsの合成

概要

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12,15-Ethanoprostaglandins were synthesized in order to find out new drags which have a selected pharmacological activity isolated from many other inherent activities of prostaglandins. Our synthetic scheme is based on introduction of α-chain followed by ω-chain to the intermediate hemiacetal 30 derived from spiro[4,5]deca-1,4,8-trione 4. Reaction of sodium salt of cyclopentadione 1 and divinylketone 2 in DMF afforded a intermediate anion 3 which was treated with AcOH to give trione 4. The trione 4 was protected with ethylene glycol, oxidized with SeO_2 and further treated with LiCH_2CO_2^tBu to give hydroxy ester 24. Removal of the hydroxyl group from 24 was accomplished by chlorination with SOCl_2-pyridine followed by Zn-MeOH reduction. The resulting β,γ-unsaturated ketone 28 was isomerized to unsaturated ketone with NaOMe. The lactone 29 obtained from 28 by p-TsOH treatment was reduced to the key intermediate hemiacetal 30 with DIBAL. Introduction of α-chain to 30 by the conventional methods to furnish 31, which was deacetalized and treated with n-AmMgBr to give desired 12,15-ethano-13,14-dihdroprostaglandin F_<2α> methyl ester 33. Selective oxidation of 33 gave the corresponding prostaglandin E type compound 37.
天然有機化合物討論会の論文
1976-09-20