The prostanoids are ubiquitous throughout mammalian biology owing to their role in the regulation of a wide range of important pathological and physiological processes. Divided into three subclasses, namely, the prostaglandins, prostacyclins and thromboxanes, the prostanoids have been implicated as local hormones for the mediation of inflammation, platelet aggregation, vasodilation and vasoconstriction.1,2 The synthesis of the prostanoids, in particular PGF2α, has attracted high levels of attention from the chemical community with many different synthetic routes developed.2 Most of these syntheses have disadvantages because of their length or poor stereoselectivity. Recent developments have facilitated the synthesis of 13 in just seven steps via key bicyclic hemiacetal 3 from commercially available starting materials (2). To demonstrate the wide application of our methodology, we incorporated hemiacetal intermediate 3 into a synthetic route for another class of prostanoids, the prostacyclins, thus allowing the preparation of α,α-difluorinated prostacyclin PGI2-F2 (4) in 9 steps from 2. Figure 1: Aggarwal synthesis of PGF2α and subsequent application of 3 to the total synthesis of 4. (1) Bergström, S.; Carlson, L. A.; Weeks, J. R. Pharmacological Reviews 1968, 20, 1. (2) Collins, P. W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533. (3) Coulthard, G.; Erb, W.; Aggarwal, V. K. Nature 2012, 489, 278.

Total synthesis of fluorinated prostacyclin PGI2-F2

251st National Meeting (2016)

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