Prostaglandin methyl ester

Synthesis of Racemic and Optically Active Prostaglandin Methyl Ester... 

Hayashi and Umemiya developed synthesis of prostaglandin methyl ester based on the Michael addition of butanedial to nitroalkene (Scheme 8.9). This synthesis also has noteworthy sustainable features a) it was performed in only three pots, including three isolations and three chromatographic purifications b) the key Michael reaction is a highly selective catal5dic reaction c) the metal-based reagents employed in the synthesis contain only nontoxic metals. 

Interest in the biosynthesis, metabolism and physiological roles of prostaglandins and related compounds has prompted extensive investigation of sensitive and selective analytical procedures. An early report in this area [302] described the preparation of TBDMS ethers of prostaglandin methyl esters and methyl ester-oximes by treating samples with 50 /il of TBDMCS (2 M in DMF) and 50 /il of imidazole (2 M in DMF) at 100 °C for 1 h). After cooling the, reaction mixture was applied to the top of a 0.5 X 3 cm column of Sephadex LH-20 swollen with heptane/ethyl acetate (3 1), and the derivatives were eluted with 4 ml of the same solvent. After evaporation of the solvent, samples were analysed by... 

Brash AR, James RL Straight-phase separation of prostaglandin methyl ester on lipophilic gels. P/LO tagtandiyu 5 441, 1974. 

Absorption spectroscopy provides an opportunity to follow concentrations of individual species with time by observing the system at more than one wavelength. An example is the dehydration of prostaglandin E methyl ester, in which the essential chemistry is shown as follows ... 

The drug is conveniently synthesized from prostaglandin I 201 methyl ester (40), which undergoes oxybromination in the presence of potassium triiodide to give 41. Treatment with DBN... 

These GC conditions are suitable for analyzing many prostaglandins, thromboxanes, leuko-trienes, and other metabolites of arachidonic acid, such as the hydroxyeicosatetraenoic (HETE) acids. However, the 5-, 12-, and 15-HETE isomers are difficult to separate using GC methods. Sometimes the methyl ester-TMS derivatives provide a better GC separation, or for ketoprostaglandins, the MO-methyl ester-TMS derivatives often give a better separation... 

The method has been used for a short asymmetric synthesis of (-)-prostaglandin Ej methyl ester (PGEj) (2-58) starting from 2-47, 2-55 and 2-56 (Scheme 2.12) [17]. The domino reaction provided 2-57 in 60 % yield as mixture of two diastereomers in reasonable stereoselectivity (trans-threo trans-erythro ratio 83 17). Further transformations led to 2-58 in an overall yield of 7% and 94% ee in seven steps. 

A repetition of in situ experiments with the yellowhead wrasse, partially in response to the above criticisms, again showed that fish developed a learned aversion to otherwise palatable food that had been adulterated with 15P-PGA2 [99], This was presumably due to the emetic properties of PGA2. It was pointed out that methyl esters of prostaglandins are also known to possess emetic properties [104], and reasoned that if the 15-acetoxy ester inhibits the emetic properties of PGA2, then it is likely to be quickly lost because of its known lability, especially in the presence of coral esterase. Further, the acidic environment in the stomachs of predatory fish would promote hydrolysis of these labile esters. 

A guinea pig ileum bioassay was used to detect and aid in the isolation of a smooth-muscle-contracting substance from the Japanese gorgonian coral Euplexaura erecta [108]. This process led to the isolation of prostaglandin F2a (17) from the MeOH extract of the coral. Its identification was based on comparison with authentic PGF2a and its methyl ester by TLC, and comparison with authentic methyl PGF2a trimethylsilyl ether by mass spectrometry. Because of the nature of the techniques employed, some aspects of the stereochemistry in this isolate of PGF2a remain uncertain. 

Synthesis of polydeuteriated 9 (O)-methano-A619,t-prostaglandin l-i methyl esters... 

Synthesis of di-tritiated 9-(0)-methano-A6<9a)-prostaglandin /7 methyl esters... 

Starting with 3 GBq [nC]carbon dioxide produced in a 14N(p,a)11C nuclear reaction, the radiochemical yield of 165 was 0.5 GBq at the end of preparative purification performed in Sep-Pak C18 columns. The methyl esters of prostaglandins have a high affinity for the specific binding sites141. 

On the other hand, treatment of 11-nor PGE2 methyl ester (216) with an excess of o-mesitylenesulfonylhydroxylamine in CH2C12 at 0 °C, followed by passage of the reaction mixture through a bed of basic alumina yielded regioselectively the y-lactam prostaglandin (217)12). 

Very recently, a catalytic enantioselective route to prostaglandin i methyl ester was developed based on a tandem 1,4-addition-aldol reaction [84]. 

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