The prostaglandin F_2α analogues travoprost (2) and bimatoprost (3) have potent topical ocular hypotensive activity. A novel convergent synthesis of the title class of prostanoids was developed employing alkylation of the structurally advanced phenylsulfone (5Z)-(+)-4 with an enantiomerically pure (S)-4-phenyl-1-iodo-2-(triethylsilyloxy)butane, providing a route suitable for commercial scale production of latanoprost (1).¹ As a result of growing demand for hypotensive PGF_2α analogues in the pharmaceutical market, the new convergent strategy has recently been applied for the syntheses of travoprost (2) and bimatoprost (3).² The Julia-Lythgoe olefination of the phenylsulfone (5Z)-(+)-4 with novel enantiomerically pure aldehyde ω-chain synthons, followed by hydrolysis of protecting groups and final esterification or amidation yielded travoprost (2) or bimatoprost (3).

The new procedure overcame most disadvantages of the classic Corey synthesis and ensured the absence of an appreciable quantity of the undesired 15-epi isomer of travoprost (2) or bimatoprost (3). The novel convergent strategy allows the synthesis of a whole series of PGF_2α analogues and related compounds from a common and structurally advanced prostaglandin phenylsulfone (5Z)-(+)-4. The main advantages are the preparation of high purity prostanoids and the application of comparatively inexpensive reagents.

1.       (a). J. G. Martynow, J. Jóźwik, W. Szelejewski, O. Achmatowicz, A. Kutner, K. Wiśniewski, J. Winiarski, O. Zegrocka-Stendel, P. Gołębiewski. Eur. J. Org. Chem. 2007, 689. (b) J. G. Martynow, J. Jóźwik, W. Szelejewski, O. Achmatowicz, A. Kutner, K. Wiśniewski, J. Winiarski, O. Zegrocka-Stendel, P. Gołębiewski. US Patent no. 7,897,793 B2; Mar. 1, 2011.

2.       I. Dams, M. Chodyński, M. Krupa, A. Pietraszek. M. Zezula, P. Cmoch, M. Kosińska and A. Kutner. Polish patent applications P.398388 and P.398389.

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