Stereocontrolled synthesis of enantiopure anticancer cyclopentenone prostaglandin analogues: (−)- and (+)-TEI-9826

The synthesis of both enantiomers of TEI-9826 has been accomplished in seven steps with an overall yield of 44% starting from diastereomeric camphor protected 3-[(dimethoxyphosphoryl)methyl]-4,5-dihydroxycyclopent-2-enones. The key steps include a fully diastereoselective hydrogenation of the endocyclic carbon–carbon double bond in the cyclopentenone ring controlled with a chiral diol moiety and the conversion of the latter into a new transposed olefinic bond.

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3-Hydroxy-4-n-octylcyclopentanoneC13H24O2Ee = 100%[α]D20=+126.0 (c 1.2, CHCl3)Source of chirality: (+)-camphorAbsolute configuration: (3R,4S) (this work)

Methyl 7-(2-n-octyl-5-oxocyclopenten-3-ylidene)heptanoateC21H34O3Ee = 100%[α]D20=-150.1 (c 0.9, CHCl3)Source of chirality: (+)-camphorAbsolute configuration: (R) (literature data)

4-n-Octylcyclopent-2-enoneC13H22OEe = 100%[α]D20=-132.6 (c 1.8, CHCl3)Source of chirality: (+)-camphorAbsolute configuration: (S) (literature data)