Prostaglandins synthetic utility

Since its discovery two decades ago, the reversible interconversion of allylic sulfenates to sulfoxides has become one of the best known [2,3]-sigmatropic rearrangements. Certainly this is not only because of the considerable mechanistic and stereochemical interest involved, but also because of its remarkable synthetic utility as a key reaction in the stereospecific total synthesis of a variety of natural products such as steroids, prostaglandins, leukotrienes, etc. 

The synthetic utility of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of p-blockers. Allyl derivative (25) may be converted into (3)-paraconic acid [4694-66-0] ((JT)-5-oxo-3-tetrahydrofurancarboxylic acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cyclic monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

The next example makes more involved use of these [2,3]-sigmatropic allylic sulfoxide-allylic alcohol rearrangements. It comes from the work of Evans (he of the chiral auxiliary) who, in the early 1970s, first demonstrated the synthetic utility of allylic sulfoxides. Here he is using this chemistry to make precursors of the prostaglandins, a family of compounds that modulate hormone activity within the body. 

A superb example of the synthetic utility of the iodolactonization reaction in organic synthesis is the conversion of the bicyclo[2.2.1]heptenone below into the Corey lactone. The latter compound possesses four contiguous stereogenic centers and is an important precursor for the synthesis of prostaglandins. 

Stereoselectixe reduction of ketones. Corey s synthesis of prostaglandins utilizes as a key intermediate the cnone (I). One major synthetic problem is the stereoselective reduction of the carbonyl group to the desired 15S alcohol (Ila). Reduction with various borohydridc reagents or various trialkylborohydrides (R, R2R3BH Li ) affords about... 

The electrophilic reactivity of the j3-carbon in an a/S-unsaturated aldehyde is reversed in l,3-bis(methylthio)allyl-lithium (151), derived by metallation of l,3-bis(methylthio)-2-methoxypropane with lithium di-isopropylamide this reagent functions as the synthetic equivalent of the unknown p-formylvinyl anion (152) in the preparation of a number of ay -unsaturated aldehydes, as exemplified in Scheme 72. Corey has utilized this reagent further in a total synthesis of prostaglandin p2 . 

These workers (10,11) have also utilized O2 to achieve an important synthetic objective in the prostaglandin field, namely the efficient conversion of 15-R (unnatural) prostaglandins into the 15- (natural) Isomers by nucleophilic displacement. These data all demonstrate the Sjj2 inversion character of 02 reacting with alkyl halides and sulfonate esters. 

In another approach by the same group, a Diels-Alder reaction was utilized for the introduction of both side chains which led to a synthetic prostaglandin analog with cis configuration of the alkyl side chains. The 0 H OH... 

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