Prostaglandin derivatives natural products synthesis

The use of bicyclo(2,2,l)-heptane derivatives in natural product synthesis has been explored extensively by Grieco and co-workers. They have devised a synthesis of ( )-estrone based on orthoquinodimethane methodology in which e ring D component is derived stereospecihcally from the bicyclo-(2,2,l)heptane species 134 (Scheme 18). The latter and related bicycloheptanes are readily available from norbomadiene by a sequence which features e Prins reaction, devised independently by groups led by Corey and Sutherland in conjunction with their studies on prostaglandin synthesis. 

Carboxylic acids, compounds of the type RCOH, constitute one of the most frequently encountered classes of organic compounds. Countless natural products are carboxylic acids or are derived from them. Some carboxylic acids, such as acetic acid, have been known for centuries. Others, such as the prostaglandins, which are powerful regulators of numerous biological processes, remained unknown until relatively recently. Still others, aspirin for example, are the products of chemical synthesis. The therapeutic effects of aspirin, welcomed long before the discovery of prostaglandins, are now understood to result from aspirin s ability to inhibit the biosynthesis of prostaglandins. 

Baeyer-Villiger oxidation of bridged bicyclic ketones is valuable in synthesis because it provides a method for preparing derivatives of cyclohexane and cyclopentane with control of the stereochemistry of the substituent groups, and several syntheses of natural products have exploited this possibility. Thus, the lactone 64, important in the synthesis of prostaglandins, was obtained in a sequence the key step of which was the Baeyer-Villiger oxidation of the bridged bicyclic ketone 63 (6.62). 

The radical cyclization products derived from sugars are useful for the synthesis of cyclopentanoid natural products. For example, the unprecedented 1,5-trans stereochemistry seen in the case of 4,6-0-benzylidene-glucose-derived radicals can be used to prepare optically active prostaglandin intermediates such as Corey lactone 44 (Fig. 7.12) [23]. 

To the best of our knowledge, the first example of a Suzuki coupling reaction in the synthesis of a PUFA-derived natural product was disclosed in the synthesis of prostaglandin... 

Allyl epoxides are produced by the acclaimed Sharpless asymmetric epoxidation reaction [75], and are important intermediates and products. For example, an allyl epoxide is a vital part of the structure of amphidinolides, a series of unique macrolides isolated from dinoflagellates (Amphidinium sp.). Amphidinolide H (AmpH) is a potent cytotoxic 26-membered macrolide with potent cytotoxicity for several carcinoma cell lines [76]. An allyl epoxide is involved in the total synthesis of prostaglandin A2 with a cuprate reagent [77]. Allyl epoxides derived from Sharpless chemistry are a practical method for construction of polypropionate structures by Lewis acid-induced rearrangement [78,79]. Other allyl epoxides such as l,2-epoxy-3-methyl-3-butanol are useful organic intermediates for the production of a-hydroxyketones, which are used for the synthesis of various natural... 

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