Synthesis of the Primary Prostaglandins

A critical assessment of the economic practicability etc. of the various routes to similar compounds is not possible at this stage, and has not been attempted. 

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The lactone A was also used as starting material in the synthesis of the primary prostaglandins via an allylic substitution-semi-pinacolic rearrangement sequence (Ref. 2). 

Prostaglandins.—At a time when one was beginning to feel that interest in the total synthesis of the primary prostaglandins (i.e. E and F series) had evaporated, Newton and Roberts and their respective collaborators report a particularly novel route to PGp2a which starts from cyclopentadiene and involves the stereospecific formation... 

As we were beginning to feel that the dust had finally settled on the feverish activity in synthesis of the primary prostaglandins, two groups of Japanese workers have reported new and exciting syntheses of PGEi (118) during 1982. 

Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and related compounds (see Figure 39.3). Arachidonic acid is present as a component of the phospholipids of cell membranes, primarily phosphatidyl inositol and other complex lipids.1 Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 and other acyl hydrolases, via a process controlled by hormones and other stimuli (see Figure 39.3). There are two major pathways in the synthesis of the eicosanoids from arachidonic acid (see Figure 39.3). 

An alternative to blood analyses, which has been used successfully in many studies, is measurement of the prostaglandin content of urine instead [335]. Depending on the aim of the study either the primary prostaglandins (which mostly reflect the renal prostaglandin biosynthesis [128,340]) or suitable metabolites (which reflect the total body synthesis of prostaglandin [266,272]) may be monitored. 

Side chain introduction by carbopalladation has been utilized in a total synthesis of an-thramycin methyl ether (32) (Scheme Heck reaction of the alkenyl triflate 30 with acrylamide installs the necessary three-carbon chain in moderate yield. The desired alkene geometry and oxidation state are observed in the dienamide 31 with no need for protection of the primary amide. The organopalladium precursor can also be part of the side chain being introduced as illustrated in a synthesis of prostaglandin E2 33. ... 

The literature on the synthesis of prostaglandins is now very substantial, the number of published papers having increased some eight-fold since the last review [ 1 ]. Major advances have included new and improved syntheses of the primary (E and F) prostaglandins, syntheses of PGs A, C and D, thromboxane Bi and prostacyclin (PGI), and the preparation of numerous prostaglandin analogues. Selected references are included here with the object of illustrating the main trends in this work. 

Prostaglandins, Methylenomycins, and Related Compounds.—The major development in prostaglandin synthesis during 1980 has come from Paquettes group, which has described an extraordinarily facile approach to all the primary prostaglandins based simply on anionic [3,3] sigmatropic shift from the carbinol (83), produced from commercially available 1,5-cyclo-octadiene (Scheme 11). Elaboration of the aldehyde (84), as shown in Scheme 11, then provides a very attractive route to the well-known Corey aldehyde (85). 

Even more extensive optimization of reaction conditions was performed in the group of Aggarwal [10]. With the aim to synthesize prostaglandins, their primary goal was to obtain the intermediate bicyclic lactol 30, which allows stereoselective conjugate addition of organocuprates and derivatization of the cyclopentane scaffold. For the synthesis of the bicyclic intermediate, the researchers envisioned an asymmetric aldol dimerization of succinaldehyde (23) by means of a proline-based... 

The cytochrome P450 (CYP450) enzyme superfamily is the primary phase I enzyme system involved in the oxidative metabolism of drugs and other chemicals. These enzymes also are responsible for all or part of the metabolism and synthesis of a number of endogenous compounds, such as steroid hormones and prostaglandins. 

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