Synthesis of prostaglandin analogues, latanoprost and bimatoprost, using organocatalysis via a key bicyclic enal intermediate.

Publisher: American Chemical Society Country of Publication: United States NLM ID: 100890393 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-7052 (Electronic) Linking ISSN: 15237052 NLM ISO Abbreviation: Org Lett Subsets: MEDLINE

Original Publication: Washington, DC : American Chemical Society, c1999-

Amides/*chemical synthesis ; Cloprostenol/*analogs & derivatives ; Dinoprost/*chemical synthesis ; Prostaglandins F, Synthetic/*chemical synthesis ; Prostaglandins, Synthetic/*chemical synthesis; Aldehydes/chemistry ; Amides/chemistry ; Bimatoprost ; Cloprostenol/chemical synthesis ; Cloprostenol/chemistry ; Dinoprost/analogs & derivatives ; Dinoprost/chemistry ; Latanoprost ; Molecular Structure ; Prostaglandins F, Synthetic/chemistry ; Prostaglandins, Synthetic/chemistry

Two antiglaucoma drugs, bimatoprost and latanoprost, which are analogues of the prostaglandin, PGF2α, have been synthesized in just 7 and 8 steps, respectively. The syntheses employ an organocatalytic aldol reaction that converts succinaldehyde into a key bicyclic enal intermediate, which is primed for attachment of the required lower and upper side chains. By utilizing the crystalline lactone, the drug molecules were prepared in >99% ee.

Erratum in: Org Lett. 2023 Aug 25;25(33):6235. (PMID: 37566563)

0 (Aldehydes)
0 (Amides)
0 (Prostaglandins F, Synthetic)
0 (Prostaglandins, Synthetic)
4208238832 (Cloprostenol)
6Z5B6HVF6O (Latanoprost)
8C6G962B53 (3-hydroxybutanal)
B7IN85G1HY (Dinoprost)
QXS94885MZ (Bimatoprost)

Date Created: 20150114 Date Completed: 20150408 Latest Revision: 20230811

20240829

10.1021/ol503520f

25582321