Rapid chromatographic technique for preparative separations with moderate resolution
Abstract: (11) Potassium ferricyanide has previously been used to convert w'c-1,2-dicarboxylate groups to double bonds. See, for example, L. F. Fieser and M. J. Haddadln, J. Am. Chem. Soc., 86, 2392 (1964). The oxidative dldecarboxylation of 1,2-dlcarboxyllc acids is, of course, a well-known process. See Inter alia (a) C. A. Grob, M. Ohta, and A. Weiss, Helv. Chim. Acta, 41, 1911 (1958); and (b) E. N. Cain, R. Vukov, and S. Masamune, J. Chem. Soc. D, 98 (1969).
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TL;DR: Investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of thePyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta.
Abstract: We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al Chem Biol 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERalpha than on the ERbeta subtype (Sun et al Endocrinology 1999, 140, 800-804) To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERalpha-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERalpha The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERalpha with high affinity (ca 50% that of estradiol), and it has a 410-fold binding affinity preference for ERalpha It also activates gene transcription only through ERalpha Thus, this compound represents the first ERalpha-specific agonist We investigated the molecular basis for the exceptional ERalpha binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling These investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERalpha
751 citations
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TL;DR: A photoredox-catalyzed C–H arylation reaction for the construction of benzylic amines is discovered, an important structural motif within pharmaceutical compounds that is not readily accessed via simple substrates.
Abstract: Serendipity has long been a welcome yet elusive phenomenon in the advancement of chemistry. We sought to exploit serendipity as a means of rapidly identifying unanticipated chemical transformations. By using a high-throughput, automated workflow and evaluating a large number of random reactions, we have discovered a photoredox-catalyzed C–H arylation reaction for the construction of benzylic amines, an important structural motif within pharmaceutical compounds that is not readily accessed via simple substrates. The mechanism directly couples tertiary amines with cyanoaromatics by using mild and operationally trivial conditions.
667 citations
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TL;DR: Methods currently used for the quantitative analysis of saponins, sapogenols, and glycoalkaloids are critically considered; advances in the use of newer methods being emphasized.
Abstract: Saponins occur widely in plant species and exhibit a range of biological properties, both beneficial and deleterious. This review, which covers the literature to mid 1986, is concerned with their occurrence in plants and their effects when consumed by animals and man. After a short discussion on the nature, occurrence, and biosynthesis of saponins, during which the distinction between steroidal and triterpenoid saponins is made, the structures of saponins which have been identified in a variety of plants used as human foods, animal feedingstuffs, herbs, and flavorings are described. Many of these compounds have been characterized only during the last 2 decades, and modern techniques of isolation, purification, and structural elucidation are discussed. Particular consideration is given to mild chemical and enzymatic methods of hydrolysis and to recent developments in the application of NMR and soft ionization MS techniques to structural elucidation. Methods currently used for the quantitative analysis of saponins, sapogenols, and glycoalkaloids are critically considered; advances in the use of newer methods being emphasized. The levels of saponins in a variety of foods and food plants are discussed in the context of the methods used and factors affecting these levels, including genetic origin, agronomic, and processing variables, are indicated. Critical consideration is given to the biological effects of saponins in food which are very varied and dependent upon both the amount and chemical structure of the individual compounds. The properties considered include membranolytic effects, toxic and fungitoxic effects, adverse effects on animal growth and performance, and the important hypocholesterolemic effect. A final section deals briefly with the pharmacological effects of saponins from ginseng, since use of this plant is increasing in certain sections of western society as well as being traditional in the Orient.
635 citations
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TL;DR: By analyzing the sign of the difference in chemical shifts for a number of analogous pairs of protons in the diastereomeric esters (or amides), the absolute configuration of the original carbinol (or amino) stereocenter can be reliably deduced.
Abstract: This protocol details the most commonly used nuclear magnetic resonance (NMR)-based method for deducing the configuration of otherwise unknown stereogenic, secondary carbinol (alcohol) centers (R1R2CHOH (or the analogous amines where OH is replaced by NH2)). This 'Mosher ester analysis' relies on the fact that the protons in diastereomeric alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA) esters (i.e., those derived from conjugation of the carbinol under interrogation with MTPA) display different arrays of chemical shifts (deltas) in their 1H NMR spectra. The protocol consists of the following: (i) preparation of each of the diastereomeric S- and R-MTPA esters and (ii) comparative (Delta delta(SR)) analysis of the 1H NMR spectral data of these two esters. By analyzing the sign of the difference in chemical shifts for a number of analogous pairs of protons (the set of Delta delta(SR) values) in the diastereomeric esters (or amides), the absolute configuration of the original carbinol (or amino) stereocenter can be reliably deduced. A typical Mosher ester analysis requires approximately 4-6 h of active effort over a 1- to 2-d period.
608 citations
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TL;DR: Results suggest that constituents 1-6 are very potent antioxidants toward LDL oxidation with Glabridin being the most abundant and potent antioxidant.
549 citations