Prostaglandin E2-1,15-lactone

A particularly flexible and novel entry into prostaglandins and analogs, either by RCAM (463—>464) or by the intermolecular variant ACM (462+466 -+467) from a common intermediate (462), is outlined in Scheme 93 [190]. Prostaglandin E2-1,15-lactone (465), an ichthyotoxic compound produced by a marine nudibranch for defense purposes, was produced in Fiirstner s laboratory along the RCAM-based sequence 462 463—>464-+465. Alternatively, the... 

A. Furstner and co-workers also showed that RCAM is indeed a very mild method, because during their stereoselective total synthesis of prostaglandin E2-1,15-lactone, the Mo[N-(f-Bu)(Ar)3]-derived catalyst tolerated a preexisting double bond and a ketone functionality. Chromatographic inspection of the reaction mixture revealed that no racemization took place before or after the ring closure, and the ee of the substrate and the product were virtually identical. 

Furstner, A., Grela, K. Ring-closing alkyne metathesis application to the stereoselective total synthesis of prostaglandin E2-1,15-lactone. Angew. Chem., Int. Ed. Engl. 2000, 39, 1234-1236. 

Metathesis with alkynes is also quite useful in synthesis,particularly for internal alkynes although terminal alkynes are not good partners in this reaction.358 internal metathesis reactions with alkynes are known,including the conversion of 439 to 440 (in 73% yield) in FUrstner s synthesis of prostaglandin E2-1,15-lactone.360 Note the use of a molybdenum metathesis catalyst for this reaction. Diynes also react with alkynes in an intermolecular reaction to form aromatic rings. An example is the conversion of 441 to a 6 1 mixture of 442/443, in 82% yield.36la a similar, palladium-catalyzed cycloaromatization is also known.362 The metathesis disconnections are... 

Scheme 11.11 shows the high-yield formation a 13-membered cycloalkyne by RCAM and the subsequent reduction of the C=C bond. These were key steps in the synthesis of the 1,15-lactone of prostaglandin E2, which is a powerful defense chemical stored in mucous membranes of a species of nudibranch.72 This lactone is also important because hydrolysis yields prostaglandin E2, a potent biomediator in mammals that regulates uterine contractions and gastric secretion. 

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