54324-79-7Relevant articles and documents
A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis
Chen, Fener,Huang, Zedu,Jiang, Meifen,Li, Weijian,Tang, Pei,Ye, Baijun,Zhang, Guo-Tai,Zhu, Kejie
, p. 10362 - 10370 (2021/08/16)
Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone6aguided by biocatalytic retrosynthesis, in 11-12 steps with 3.8-8.4% overall yields. An unprecedented Baeyer-Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of6a(99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones12(87?:?13 to 99?:?1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper(ii)-catalyzed regioselectivep-phenylbenzoylation of the secondary alcohol of diol10(9.3?:?1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.
N-(Methanesulfonyl)-16-phenoxyprostaglandincarboxamides: Tissue-Selective, Uterine Stimulants
Schaaf, Thomas K.,Bindra, Jasjit S.,Eggler, James F.,Plattner, Jacob J.,Nelson, A. James,et al.
, p. 1353 - 1359 (2007/10/02)
In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro and in vivo models.Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-ω-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).