Prostaglandins (PGs), which play an important role in human physiology, have attracted much interest in their pharmacology and therapeutic potential. Development of a general and efficient organic synthesis of PGs is very important for it is the only viable means to supply sufficient quantities and to create more effective compounds. We have succeeded in establishing a two-component coupling synthesis of PGs as an industrially viable process by developing highly efficient and practical syntheses of the following requisite key intermediates ; the
endo-enone bearing an α side chain 1, the
exo-enone bearing an ω side chain 2, and the ω side chain unit (γ-iodo allylic alcohols). The key features of our synthesis of 1 and 2 are illustrated in equation 7. The key intermediate, enone 9, is prepared efficiently from readily available chiral epoxy alcohol 3. The enone is treated with an organocopper compound derived from the α side chain unit to give 1
via a 1, 4-addition reaction, which is accompanied by the elimination of the alkoxy group. Compound 9 is also converted into 2, which involves the organocuprate conjugate addition of the ω side chain to 10, obtained from 9 by the Michael addition of Et
2NH. Optically active γ-iodo allylic alcohols, the ω side chain unit, are prepared by highly efficient kinetic resolution of the corresponding racemic alcohols by the Katsuki-Sharpless asymmetric epoxidation.
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