Conjugate Addition-Alkylation Route to Prostaglandins

A short three-component route to prostaglandins was developed involving a number of novel steps, several of which were based on special properties of the (9-methyloxime function. 

A direct synthesis of the fragment A was also achieved starting from diethyl (5,5)-tartrate. 

Two different routes to PCs via bicyclo[3.1.0]hexane intermediates are shown. In route 1 stereo- and position-specific addition of dichloroketene to a bicyclo[3.1.0]hexene provided the framework for elaboration to prostanoids. Route 2 featured stereospecific internal cyclopropanation and stereospecific Sn2 displacement of carbon to establish the prostanoid nucleus. 

The low position selectivity in the epoxide opening step of this early synthesis was improved in a later study (Ref. 2). 

The possibility that 11-desoxyprostaglandins might exhibit tissue selectivity in therapeutic applications provided an incentive to develop a short synthetic route to this series (Ref. 1). 

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