An Improved and Efficient Process for the Preparation of (+)‐cloprostenol

Abstract

An improved and efficient synthesis of (+)-cloprostenol has been accomplished in nine steps and 26% overall yield from commercially available (-)-Corey lactone 4-phenylbenzoate alcohol . The present route avoids tedious purifications and requires only one column chromatography operation, which reduces the generation of waste and is suitable for large-scale preparation.

A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis

“…The configuration of the newly generated stereogenic center (C-15, prostaglandin numbering) was assigned as α by comparing to that of 13a prepared using (−)-DIP-Cl-mediated reduction. 28 From 13a , hydrolysis of the PPB ester to alcohol, followed by the DIBAL-H mediated reduction of the lactone to the hemiacetal, and a final Wittig olefination furnished cloprostenol ( 1 ) in 44% over three steps ( Fig. 5 ).…”

Unified Strategy to Prostaglandins: Chemoenzymatic Total Synthesis of Cloprostenol, Bimatoprost, PGF2α, Fluprostenol, and Travoprost Guided by Biocatalytic Retrosynthesis

“…Pleasingly, ChKRED20catalyzed reduction of 12a under the optimized condition at a preparative-scale occurred smoothly, delivering the desired allylic alcohol 13a in 91% isolated yield with 97.9 : 2.1 dr (Table 3, entry 6). The configuration of the newly generated stereogenic center (C-15, prostaglandin numbering) was assigned to  by comparing to that of 13a prepared using (-)-DIP-Cl-mediated reduction 76 .…”

Chemical F/J‐Interconversion in the Prostaglandin Family: From Cloprostenol to Its Δ12‐J2 and 15‐Deoxy‐Δ12,14‐J2 Derivatives

“…[13][14][15] In recent years, a number of elegant approaches to the synthesis of cyPG1-4 and others were suggested by the teams of Nicolaou, [16] Aggarwal, [17] Grubbs, [18] and Chen. [19] In this work, we aimed at developing a conversion of F-type PG into Δ 12 -and Δ 12,14 -PGJ with a change in the bioactivity to the anticancer profile, using cloprostenol 5 [20] (Pharmaceuticals based on cloprostenol 5 (Estrumate, Oestrofane etc) are widely used in practice for induction of labor, synchronization of estrus, and treatment of postpartum complications in female farm animals), an analogue of prostaglandin F 2a , as an example (Scheme 1). This is important because the majority of F-type PGs are commercially available, less expensive, and more stable in storage than PGJs.…”