ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The synthesis of the TXA2/PGH2 receptor antagonist 6 from the known chiral intermediate (-)-8 is described. The critical reaction is the inversion of C-5 in 11a and 11b by an intramolecular cyclization reaction induced by nucleophilic reagents as shown in structure 13a. The key intermediate 22 was prepared in 26.5 % yield in five steps. Diastereoselectivity is high in all but one of the steps, the Reformatsky reaction, which leads to equal amounts of 11a and 11b. The design of 6 is based on the dioxabicycloheptane nucleus characteristic of TXA2 (1), which has been stabilized by fluorination. To this nucleus the two side chains are attached in cis orientation, and the omega-chain is modified as reported for the receptor antagonist (-)-5, which in turn is an analogue of PGH2 (3). These changes in the side chains have the effect of converting the powerful agonist 2 (DFTXA2) into a receptor antagonist devoid of agonist activity, which binds to the receptor with nanomolar affinity. These findings lend support to the view of a single TXA2/PGH2 receptor.

Synthese d'acylals, hemihalogenoacetals et hemiacetals a partir de dimethylacetals de pyruvaldehyde et de phenyl-4 oxo-2 butene-2 al

A pheromone mixture containing enantiomerically pure (−)-α-multistriatin of known absolute configuration prepared by total synthesis was found to be as attractive as the natural pheromone to the smaller European elm bark beetle,Scolytus multistriatus, a vector of Dutch elm disease. Its (+)-enantiomer, on the other hand, was no more active than controls in both laboratory and field tests, and at high levels it appeared to inhibit the response to the (−)-enantiomer.

Prostaglandin F2 alpha (PGF2 alpha) was identified as a luteolytic hormone in sheep (Nature, New Biol. 238, 129, 1972). Attempts to use PGF2 alpha for the pharmacological control of luteolysis in normal cycling sheep met with only partial success due to the rapid clearance of PGF2 alpha from the blood. In addition treated animals showed moderate to severe cardiovascular and gastrointestinal side effects. Accordingly, experiments were carried out to determine whether PG analogs might be more effective as pharmacological luteolytic agents. These compounds, which consisted of a number of the 13-dehydro analogs of PGF2 alpha, were administered to both sheep and monkeys either directly into the ovary or into the systemic circulation to examine them respectively for direct luteolytic activity and for resistance to metabolism. In addition in both the sheep and the monkey smooth muscle activity of the analogs was determined by recording uterine contractions in vivo. Several 13-dehydro analogs including some 16-fluoro derivatives were shown to have luteolytic activity equal to, or in some cases greater than, PGF2 alpha itself. Furthermore most of these compounds showed a marked resistance to the 15-OH-PG-dehydrogenase enzyme in vivo as evidenced by their luteolytic activity when infused intravenously. In terms of uterine contractions, several luteolytic analogs showed markedly diminished smooth muscle activity, and in some cases, complete absence of activity. These results suggest that the receptors governing the luteolytic effect on the one hand, and the smooth muscle effect on the other, possess different structural specificities. Recent studies which we have carried out on the effect of PGF2 alpha on corpus luteum (CL) blood flow support this conclusion. CL capillary blood flow was continuously monitored by means of a miniaturized Geiger-Müller probe inserted through the center of the CL in both the in situ and the autotransplanted ovary of the sheep. Capillary blood flow was measured by the clearance rate of 85Krypton injected periodically into the ovarian artery before and during the induction of luteolysis with PGF2 alpha. It was concluded that the initiation of luteolysis is not dependent on a smooth muscle effect of PGF2 alpha on the capillaries of the CL, a finding which supports the results with the synthetic analogs devoid of smooth muscle activity. More recently, in the primate model used (Macaca fascicularis) we have demonstrated that certain metabolically stable analogs are luteolytic when given intravenously, subcutaneously, or orally. These results demonstrate a rational approach to both drug synthesis and biological evaluation and suggest that a once-a-month contraceptive agent, based on a luteolytic analog of PGF2 alpha, devoid of smooth muscle activity (side effects) and metabolically stable in the bloodstream may become a reality.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA simple carbon-13 nuclear magnetic resonance spectroscopic method for distinguishing between open-chain and pseudoacid chloridesWilliam J. Elliott and Josef FriedCite this: J. Org. Chem. 1978, 43, 13, 2708–2710Publication Date (Print):June 1, 1978Publication History Published online1 May 2002Published inissue 1 June 1978https://pubs.acs.org/doi/10.1021/jo00407a037https://doi.org/10.1021/jo00407a037research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Previous studies of luteolytic 13-dehydroprostaglandins have been extended in two directions. 1) Inclusionof M. fascicularis as a primate model to demonstrate luteolysis and 2) synthesis of 16-fluorinated 13-dehydroprostaglandins to further reduce the smooth muscle stimulating activity of the non-fluorinated parents without impairment of luteolytic potency.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereocontrolled synthesis of .alpha.-multistriatin, an essential component of the aggregation pheromone for the European elm bark beetleWilliam J. Elliott and Josef FriedCite this: J. Org. Chem. 1976, 41, 14, 2475–2476Publication Date (Print):July 1, 1976Publication History Published online1 May 2002Published inissue 1 July 1976https://pubs.acs.org/doi/10.1021/jo00876a028https://doi.org/10.1021/jo00876a028research-articleACS PublicationsRequest reuse permissionsArticle Views248Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Carbon magnetic resonance T(1) relaxation and chemical shift measurements at 22.63 MHz establish hydrophobic aggregation of prostaglandin F(2alpha) in phosphate buffer solutions between 0.05 and 0.2 M. Analysis of the proton magnetic resonance spectra of prostaglandin F(2alpha) at 270 MHz by double resonance techniques yield all the proton-proton coupling constants for the five-membered ring indicating a favored half-chair conformation for the ring in which the dihedral angle for the C-8 and C-12 protons is close to 180 degrees . Effective correlation times derived from carbon magnetic resonance T(1) values for all the carbon atoms show segmental motion for ring carbon C-10 and in the aliphatic portions of both side chains, while the double bonded portions of the side chains and the ring carbons act as a more rigidly interconnected network. Chemical shift changes in the carbon magnetic resonance and proton magnetic resonance spectra upon aggregation suggest that the 5-6 double bond, C-7, and C-9 participate in the aggregation process.

Two new immunogenic opioid-protein conjugates were prepared. Codeine-6-hemisuccinate was synthesized from the reaction of codeine with succinic anhydride and hydromorphone-6-carboxymethyloxime was synthesized from the reaction of hydromorphone with α-aminoxyacetic acid. Both opioids were attached covalently to bovine serum albumin using the mixed anhydride procedure and employed as immunogens in rabbits. Antibody measured by the ammonium sulfate method showed increases in titer and avidity following subsequent immunizations. The specificities of both antisera were studied by competitively inhibiting the binding of labeled opioid to antibody by the prior addition of increasing concentrations of various unlabeled opioids. The ranges of immunoreactivity of both antisera were different and corresponded closely to the structures of the respective immunizing haptens. These observations suggest that antibodies prepared against codeine, hydromorphone, and morphine may be used in combination for qualitative as well as quantitative determinations of opioids in biologic fluids.

High-resolution pulsed Fourier-transform nuclear magnetic resonance spectroscopy at 22.63 MHz was used to observe the proton-decoupled natural-abundance (13)C nuclear magnetic resonance spectra of CDCl(3) solutions of the methyl esters of prostaglandins F(1alpha), 15-epi-F(1alpha), F(2alpha), F(2beta), E(2), A(2), 13-dehydro-F(2alpha), 13-dehydro-F(3alpha), two intermediates on the synthetic pathway to 13-dehydro-PGF(3alpha), and of 7-oxa-PGF(1alpha). All resonances were assigned by chemical shift comparisons and single-frequency offresonance proton decoupling. With two exceptions, all the lines of the spectra are well-resolved single-carbon resonances. Those due to the cyclopentane and vinyl carbons are most sensitive to structural changes. Some of these effects can be rationalized in terms of the preferred conformations of the molecules.

Abstract Antisera reacting with morphine were produced in rabbits by immunization with morphine-6-succinyl-bovine serum albumin. The antibody assay employed ammonium sulfate precipitation of antibody-14C-morphine complexes. The specificities of the sera were measured by prior incubation of appropriate serum dilutions with increasing concentrations of various unlabeled opioids before the addition of 14C-morphine. Opioids differed in their ability to inhibit interaction of 14C-morphine and antibody; concentrations inhibiting binding of 88 pmol/ml of 14C-morphine by 50% were: morphine-6-hemisuccinate, 0.052 nmol/ml; heroin, 0.10 nmol/ml; morphine, 0.11 nmol/ml; codeine, 0.16 nmol/ml; hydromorphone, 0.50 nmol/ml; nalorphine, 2.1 nmol/ml; meperidine, 80.0 nmol/ml; naloxone, 30% inhibition at 1.0 × 103 nmol/ml. Variations in the ability to inhibit 14C-morphine binding were related to the nature of the structural dissimilarities between the competing compound and the homologous hapten. Differences in I50 values for the opioids studied were reflections of inhibition curves with differing slopes. Such observations allow the possibility of both qualitative and quantitative analyses in assay systems.

E. W. Yankee, C. H. Lin and J. Fried, J. Chem. Soc., Chem. Commun., 1972, 1120 DOI: 10.1039/C39720001120

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of (+)- and (-)-7-oxaprostaglandin F1.alpha. and their 15-epimersJosef Fried, M. M. Mehra, and W. L. KaoCite this: J. Am. Chem. Soc. 1971, 93, 21, 5594–5595Publication Date (Print):October 1, 1971Publication History Published online1 May 2002Published inissue 1 October 1971https://pubs.acs.org/doi/10.1021/ja00750a057https://doi.org/10.1021/ja00750a057research-articleACS PublicationsRequest reuse permissionsArticle Views53Altmetric-Citations33LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

WE report here the synthesis of substances, structurally related to the prostaglandins, capable of selectively antagonizing the smooth muscle effects of both prostaglandins E1 and F1α. The availability of specific antagonists of prostaglaiidin may help solve problems about the physiological roles of the prostaglandins1.

A chromatographic method involving medium-pressure liquid chromatography on alumina impregnated with silver nitrate is described for the separation of a series of closely related C27 sterol precursors of cholesterol differing only in the number and location of olefinic double bonds. The features of the described system are compared with those of previously described thin-layer, gas-liquid, gravity column, and high-pressure liquid chromatographic methods.