Strategy prostaglandin synthesis

Scheme 5. Larock s palladium-promoted, three-component coupling strategy for prostaglandin synthesis.

Compound (28, R= SlMogBu-t) is an important intermediate in prostaglandin synthesis and can indeed be made by this strategy. 

The prostaglandin family constitutes one of the most pharmacologically active low molecular-weight natural products. Combinatorial access to prostaglandins is based on two main strategies of synthesis of its E- and F-series developed by Janda and Chen ° ° and F.llman et al. ° In the... 

Before proceeding, it is important to note that it is the conversion of the a-chloronitrile to a ketone (a functional group transformation) that establishes the a-chloroacrylonitrile as a ketene equivalent in Diels-Alder chemistry. a-Chloroacrylonitrile is not the only ketene equivalent that has been used in Diels-Alder chemistry, nor in this strategy for prostaglandin synthesis. Reviews have been written on this topic. What is perhaps most important is the development of the concept of equivalencies that was occuring at the time this synthesis was undertaken. We will see this concept again. 

Table 11.3 Prostaglandin synthesis according to a two-component strategy.

Scheme 11.61 Prostaglandin synthesis according to a three-components strategy in which both side chains are installed as organocuprate reagents.

Examples are the synthesis of prostaglandin F2 and erythronolide A (8) from D-glucose, by Stork [20] and Hanessian [19] and their coworkers, respectively, whose retrosynthetic pathways are shown in Schemes 9.9 and 9.10. For more details concerning this strategy, known as "the chiron approach", see the book by Hanessian [19]. 

New applications continue to demonstrate the enormous versatility of RCM for organic synthesis. Examples include triple ring closing (Eq. 48) and alkyne metathesis, an example being that of cross-metathesis that provides an efficient synthetic strategy for prostaglandin E2 (Eq. 49). Amines and alcohols deactivate metathesis catalysts, but their protection as ethers, esters, and amides allows them to be incorporated into the designated transformation. 

---