15,16-dimethyl-prostaglandin

Bickel, M., and G.L. Kauffman, Jr. 1981. Gastric gel mucus thickness Effect of distention, 16,16-dimethyl prostaglandin e2, and carbenoxolone. Gastroenterology 80 770. 

The Heidenhain pouch preparation was used by Carter and Grossman (1978), Kauffman et al. (1980) to study the effect of luminal pH on acid secretion evoked by topical and parenteral stimulants and the effect of topical and intravenous 16,16-dimethyl prostaglandin E2 on gastric bicarbonate secretion. 

Karim, S. Ratnam, S. Termination of pregnancy with vaginal administration of 16, 16 dimethyl prostaglandin E2 p-benzaldehyde semicarbazone ester. Br. J. Obstet. Gynecol. 1977, 84, 135-137. 

Dimethyl-prostaglandin E2 from Plasma Using Deuterated Carrier and Gas Chromatography-Mass Spectrometry... 

Gemeprost (73 16.16-dimethvl-trans-A -prostaglandin-E]) is dramatically more potent on a dosage basis as an abortifacient than prostaglandin E2 itself and has fewer side effects. The gem-dimethyl groups at C-16 protect the alcohol moiety at C-15 from rapid metabolic oxidation. 

Included among other differentiating cell lines which have been established in culture, is the human promyelocytic cell line HL-60, which differentiates into more mature myeloid cells upon treatment with retinoic acid and prostaglandin E] (PGEi). Friend erythroleukemia cells differentiate into hemoglobin-producing cells when treated with either dimethyl sulfoxide, or hexamethylene bis-acetamide. 

Using dimethyl 3,4,5,6-[2H4]-2-oxoheptylphosphonate, 36, prepared in two steps as shown in equation 14, the title prostaglandin D2, 35, has been synthesized34 in thirteen steps (equation 15). 

In a similar manner, Brummond et al. demonstrated the first total synthesis of 15-deoxy-A12,14-prostaglandin J2 (162) that was completed using a silicon-tethered allenic Pauson-Khand reaction to obtain the highly unsaturated cyclopentenone substructure [36]. Treatment of alkynylallene 160 with molybdenum hexacarbonyl and dimethyl sulfoxide affords the desired cycloadduct 161 in 43% yield (Scheme 19.30). Trienone 161 was obtained as a 2 1 Z E mixture of isomers in which the Z-isomer could be isomerized to the desired E-isomer. The silicon tether was cleaved and the resulting product converted to 15-deoxy-A12,14-prostaglandin J2 (162). 

Rush B, Merritt MV, Kaluzny M, et al. 1986. Studies on the mechanism of the protective action of 16,16-dimethyl PGE2 in carbon tetrachloride induced acute hepatic injury in the rat. Prostaglandins 32 439-455. 

Thong KJ, Robertson AJ, Baird DT. A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester). Prostaglandins 1992 44(l) 65-74. 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

The reagent was used by Corey and Kim in an improved synthesis of prostaglandins. Thus oxidation of the hydroxy acid (5) to the keto acid (6) was effected in > 90% yield with ase of N-cblorosuccinimide-dimethyl sulfide. The oxidation had been carried out previously with Jones reagent at —20° in about 70% yield. The carboxyl function... 

A case where acid-base chemistry competes with cyclization is found in efforts to construct an analog of the Corey lactone, a substance that has often served as a prostaglandin precursor [37]. The enantiomerically pure unsaturated ester 135 was assembled and subjected to the conditions indicated in Scheme 14. Dimethyl a-methylmalonate was used as the proton donor to avoid the competitive 1,4-addition of the conjugate base to 135 that occurs when the less hindered dimethyl malonate is used as the proton source. 

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