Prostaglandin synthesis Subject

Loop diuretics induce renal prostaglandin synthesis, and these prostaglandins participate in the renal actions of these drugs. NSAIDs (eg, indomethacin) can interfere with the actions of the loop diuretics by reducing prostaglandin synthesis in the kidney. This interference is minimal in otherwise normal subjects but may be significant in patients with nephrotic syndrome or hepatic cirrhosis. 

Since R-48 is also an important versatile synthon for prostaglandin synthesis, there has been interest in devising asymmetric methods for its preparation. Japanese workers 7 subjected a 1 1 mixture of cis and trans 44 to esterases from baker s yeast and were able to obtain the optically active (R,R)-45, (R,R)-46 and (S)-predominant 47. Thus a simultaneous kinetic resolution of the dlacetate (44) and asymmetric synthesis of the monoacetate (46) were effected by this hydrolysis. These were converted to prostaglandin synthons.6 ... 

Nonimmunologic contact urticaria (NICU) occurs in individuals not sensitized to the contactant, i.e., almost any normal subject. The mechanism of action is the result of a direct release of vasoactive substances, which causes a localized response [20]. Prostaglandins are mediators in the reaction to at least benzoic and sorbic acids and to methyl nicotinate, and systemic or topical inhibitors of prostaglandin synthesis inhibit the reaction to these substances [21-23]. Ultraviolet radiation (UVB and UVA) has also been shown to inhibit NICU reactions to some substances [24]. The NICU reaction is often redness without edema rather than a real wheal-and-flare reaction. The appearance of clinical signs depends mainly on the duration of exposure, the concentration of the contactant and other factors, such as rubbing or scratching. The reaction usually remains localized and systemic reactions are probably... 

Isolated keratinocytes subjected to cyclic strain exhibit a significant increase in cell proliferation, DNA synthesis, and protein synthesis compared to stationary or constantly loaded cells, which appear to involve changes in cyclic AMP. Takei et al. (1997) reported a strain-induced reduction in the levels of cyclic adenosine monophosphate, protein kinase A (PKA), and prostaglandin E2 (PGE2) as compared to stationary controls. Takei et al. (1997) also studied the effects of cyclic strain on protein kinase C (PKC) activation and translocation in cultured keratinocytes. 

The synthesis of prostaglandin PGB1 as described by Morin et al. (Eli Lily Research Labs.), starts with 7-(2-methoxyphenyl)heptanoic acid 142 which is converted into 143 through Birch reduction, esterification and acetalization. Ozone cleavage of 143 and cyclization of the resulting dialdehyde affords cyclopentene carbaldehyde 144 which was subjected to ( )-selective Wittig olefination with... 

A by now classic retrosynthesis of prostaglandins PGFj and PGEj (Fig, 4) leads to the bicydic lactone [12), five-carbon phosphonium salt [13], and phosphonate [14] (19). These compounds contain all the carbon atoms of the prostaglandins and, in [12], aU but one of the chiral centers. Lactone [12] has come to be knovm genetically as the Corey lactone, and its synthesis in one enantiomeric form has been the subject of numerous complementary investigations. 

Episodes of airway obstruction or bronchoconstriction may be induced in asthmatics by exposure to stimuli to which they are sensitized, such as inhalation of a specific pollen or house dust mite, or exposure to an occupational stimulus, e.g., red cedar dust [47]. Binding of antigen (e.g., pollen) to specific receptors (antibodies) on the surface of an inflammatory cell (e.g., mast cell) results in the elaboration of prestored mediators, such as histamine, and in the synthesis of newly formed mediators, such as arachidonic acid metabolites (e.g., prostaglandins and leukotrienes). Cellular sources of the various mediators are shown in Table 3. Cytokines and chemokines are proteins that participate in pulmonary immune and inflammatory responses. While important, these have not been subjected to discussion in this chapter because these fields are changing very... 

The alterations produced by THC and other cannabinoids in biogenic amine levels as well as on uptake, release and synthesis of neurotransmitters and effects on enzymes have been the subject of numerous investigations (for reviews see [8,52,55,114,115]). It is beyond the scope of the present summary to try to analyse and put into a proper perspective the wealth of data published so far. It is our subjective view that the mode of action of cannabi-mimetic compounds is somehow directly associated with prostaglandin metabolism (see, in particular, the series of papers by Burstein [115,116]), and/or reduction of hippocampal acetylcholine turnover observed in rats [117,118]. The latter effect is enantiospecific and follows the known SAR of the cannabinoids. This in vivo selectivity of action suggests that the THC may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septalhippocampal pathway. 

Cyclopentene motifs are present in a number of biologically active molecules and natural products including terpenes and prostaglandins. As such, this rearrangement can provide rapid access to these cores in a step-economical process. Additionally, the use of substituted VCPs allows for the regio- and diastereoselective synthesis of cyclopentene building blocks that can be subjected to postreaction modification to access variety of complex molecular architectures. Finally, the introduction of heteroatoms in VCP moiety provides the opportunity to synthesize heterocyclic rings that are present in a variety of alkaloids, terpenoids, and other natural products. 

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