Incubation of prostaglandin D2 (PGD2) with human plasma yielded a product that has been identified as 9-deoxy-9,10-didehydro-12,13-cdidehydro-13,14-dihydro-PGD2(9-deoxy-_9,9'2-13,14-dihydro-PGD2). The identification was based on mass spectrometry, UV spectrometry, mobilities and retention time on TLC and HPLC, and NMR. The conversion of PGD2 to this product was dependent on the incubation time and the amount of plasma added to a reaction mixture and was abolished by prior boiling. The conversion rate of PGD2 to this metabolite was 0.03 nmol/min per mg of protein of whole plasma at pH 8.0 at 37°C. Similar conversion was also found by incubating PGD2 with human serum albumin added at the concentration found in plasma. These results suggest that the conversion of PGD2 to this product is catalyzed by the enzymatic action of a plasma protein, probably serum albumin. The biological activities of this compound were examined in several systems. It showed negligible activity in inhibition of human platelet aggregation and relaxation of rabbit stomach strip. On the other hand, it exhibited a three times stronger inhibitory activity (IC50, 1.8 ,M) than PGD2 (IC50, 5 ,uM) on the growth of L-1210 cultured cells.Prostaglandin (PG) D2 is formed in a variety of tissues and cells and modulates their functions under various physiological and pathological conditions. For example, it is produced during platelet aggregation and works as a negative feedback modulator of the aggregation process (1-3). It is produced by mast cells during IgE stimulation and modifies the anaphylaxis process (4, 5). It is also produced in the central nervous system of mammals and is involved in brain functions such as hypothermia, sleep, and luteinizing hormone secretion (6-10). A potential antineoplastic effect of PGD2 has been reported (11) and it has been found that 9-deoxy-A9-PGD2, a dehydration product of PGD2, has about three times stronger growth inhibitory effect than PGD2 on L-1210 leukemia cultured cells (12). The present study was undertaken to explore the possible formation of this PGD2 dehydration product in mammals. We report here the conversion in human plasma of PGD2 to a compound that has been identified as 9-deoxy-A9,A12-13,14-dihydro-PGD2 and describe some properties of this metabolite.$ MATERIALS AND METHODS Materials. [5,6,8,9,12,14,15-3H]PGD2 (100 Ci/mmol; 1 Ci = 37 GBq) was purchased from New England Nuclear. PGB2, PGD2, and 9-deoxy-A9-PGD2 were synthetic products from Ono Pharmaceutical (Osaka, Japan All other chemicals were of reagent grade.Pregaration of 9-Deoxy-A9,Al2-13,14-dihydro-PGD2. 9-Deoxy-A -GD2 was synthesized as described (12), and conversion of 9-deoxy-A9-PGD2 to 9-deoxy-A9,A&12-13,14-dihydro-PGD2 was carried out as described by Bundy et al. (13) for the conversion of PGD2 to A12-13,14-dihydro-PGD2. 9-Deoxy-A9-PGD2 (48 mg) was dissolved in 3 ml of tetrahydrofuran and the solution was stirred at 4°C. 1,5-Diazabicyclo(4.3.0)non-5-ene (17.8 mg) in 0.18 ml of tetrahydrofuran was added to the solution and the mixtu...

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Additional double bonds were introduced into the alpha chain in 16-phenoxy-, 16-(3-chlorophenoxy)-, 16-[3-(tri-fluoromethyl)phenoxy]-, and 16-(4-chlorophenoxy)-17,18,19,20-tetranorprostaglandins which have antinidatory effects. Of these analogues, the delta 3-cis-delta 5 analogues 23b is 1200 times more potent than prostaglandin F2 alpha in antinidatory effect in the rat and more potent than any other known prostaglandin analogues.

The reactions of cyclohexanone and cyclopentanone oxime p-toluenesulfonates were studied. It was found that cyclohexanone oxime p-toluenesulfonate (IIIa) afforded a tetrahydroazepine derivative (Va), while cyclopentanone oxime p-toluenesulfonate (X) afforded δ-valerolactam p-toluenesulfonate (XIII), when both compounds were heated in benzene.

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