- Prostaglandins and Congeners. 27. Synthesis of Biologically Active 16-Halomethyl Derivatives of 15-Deoxy-16-hydroxyprostaglandin E2
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The 16-CF3, -CHF2, -CH2F, and -CH2Cl derivatives of DL-15-deoxy-16-hydroxyprostaglandin E2 (8a, 8b, 8c, and 8d, respectively) were prepared by conjugate addition of the lithiocuprates derived from the appropriately functionalized vinylstannanes 4 to cyclopentenone 6.Hydrolysis of the rather stable O-Si linkage at C-16 of the prostaglandin is discussed.The 13C-NMR chemical shifts of the prostaglandin analogues and intermediates are noted.
- Chen, Sow-Mei L.,Grudzinskas, Charles V.
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Read Online
- Photoenzymatic Synthesis of α-Tertiary Amines by Engineered Flavin-Dependent "ene"-Reductases
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α-Tertiary amines are a common motif in pharmaceutically important molecules but are challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent ‘ene'-reductases (EREDs) can catalyze radical additions into oximes to prepare this motif. Two different EREDs were evolved into competent catalysts for this transformation with high levels of stereoselectivity. Mechanistic studies indicate that the oxime contributes to the enzyme templated charge-transfer complex formed between the substrate and cofactor. These products can be further derivatized to prepare a variety of motifs, highlighting the versatility of ERED photoenzymatic catalysis for organic synthesis.
- Gao, Xin,Turek-Herman, Joshua R.,Choi, Young Joo,Cohen, Ryan D.,Hyster, Todd K.
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supporting information
p. 19643 - 19647
(2021/12/01)
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- Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains
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Emerging evidence suggests bromodomain-containing proteins 7 and 9 (BRD7 and BRD9) have roles in the regulation of human transcription and disease including cancer. We describe potent and selective inhibitors of the BRD7 and BRD9 bromodomains intended for use as tools to elucidate the biological roles of BRD7 and BRD9 in healthy and diseased cells.
- Hay, Duncan A.,Rogers, Catherine M.,Fedorov, Oleg,Tallant, Cynthia,Martin, Sarah,Monteiro, Octovia P.,Müller, Susanne,Knapp, Stefan,Schofield, Christopher J.,Brennan, Paul E.
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supporting information
p. 1381 - 1386
(2015/07/15)
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- Empirical method for predicting enantioselectivity in catalytic reactions: demonstration with lipase and oxazaborolidine
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We derived a novel equation capable of predicting the degree of enantioselectivity in a catalytic reaction without any knowledge of the reaction mechanism and/or the transition-state structure, and tested the validity of this equation by changing substrates systematically in the lipase or oxazaborolidine-catalyzed reactions. A good correlation was observed between the predicted and observed E values, and the stereochemistry of the products could be predicted correctly in most cases (28 out of 30).
- Ema, Tadashi,Ura, Norichika,Yoshii, Masataka,Korenaga, Toshinobu,Sakai, Takashi
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experimental part
p. 9583 - 9591
(2010/01/06)
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- Bisaryl-sulfonamides
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Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPARγ or PPARδ. In particular, the compounds of the invention modulate the function of PPARγ or PPARδ. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis.
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Page/Page column 35
(2008/06/13)
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- A general synthesis of enantiopure 1,2-aminoalcohols via chiral morpholinones
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Eleven optically active 1,2-aminoalcohols 20a-i and 26b-c were prepared from D-phenylglycine via cyclic imines 7b-i (or enamine 7a). The key step of the strategy is the diastereoselective reduction of chiral oxazinones 7a-i.
- Segat-Dioury, Fabienne,Lingibé, Olivier,Graffe, Bernadette,Sacquet, Marie-Claude,Lhommet, Gérard
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p. 233 - 248
(2007/10/03)
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- Endothelin antagonists
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A compound of the formula (I): or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.
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- ENDOTHELIN ANTAGONISTS
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A compound of the formula (I): STR1 or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.
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- ENDOTHELIN ANTAGONISTS
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A compound of the formula (I): STR1 or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.
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- The chemoselective cyclisation of unsymmetrical γ-diketones to cyclopentenones by ditected aldol reaction using a magnesium chelate
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The feasibility of synthesising disubstituted cyclopent-2-enones chemoselectively from unsymmetrical γ-diketones, using an aldol reaction directed by magnesium chelation, has been studied.Treatment of 3,3-dimethylhexane-2,5-dione 15 with aqueous sodium hydroxide (0.5 mol dm-3) gives a mixture of 3,5,5-trimethyl- 12 and 3,4,4-trimethylcyclopent-2-enone 14 in an isomer ratio 2.2:1.Insertion of an α-methoxycarbonyl grouping as a control element allows formation of a magnesium chelate 17 when treated with magnesium methoxide, and the major product is then mainly the undehydrated aldol 21.This, when treated with aqueous sodium hydroxide (0.5 mol dm-3) to dehydrate, hydrolyse and decarboxylate, gives the 3,5,5-trimethyl- and 3,4,4-trimethylcyclopent-2-enones in a nearly chemospecific ratio of 1:49.When 3-methoxycarbonyl-4,4-dimethylhexane-2,5-dione 16 is treated with aqueous sodium hydroxide (0.5 mol dm-3), omitting the magnesium methoxide treatment, the corresponding ratio of cyclopentenones was still an interesting 1:7.3.Treatment with sodium methoxide in methanol gives, by contrast γ-lactone 27.Treatment of undecane-4,7-dione 34 with aqueous sodium hydroxide (0.5 mol dm-3) at reflux gives 2,3-dipropylcyclopent-2-enone 36 and 3-butyl-2-ethylcyclopent-2-enones 35 in a ratio of almost 1:1.Treatment of 6-methoxycarbonylundecane-4,7-dione 33 with magnesium methoxide in methanol gives undehydrated aldol which when treated with aqueous sodium hydroxide gives the dipropylcyclopent-2-enone 36 and 3-butyl-2-ethylcyclopent-2-enones 35 in 9:1 ratio.Conversely, the 5-methoxycarbonyldione 32 gives a corresponding ratio of 36 to 35 of 1:9.The best ratios attained, 1:15 for 36 and 35 from 32 and 20:1 for 36 and 35 from 33, were when magnesium methoxide in refluxing benzene or toluene were employed.There is still a strong chemoselective effect when the magnesium treatment is omitted.Preliminary examination of the corresponding cyclohex-2-enone systems gave poorer chemoselectivities when either procedure was employed. 6-Methoxycarbonyldodecane-5,9-dione 52 gave 2,3-dipropyl-54 and 3-butyl-2-ethyl-cyclohex-2-enone 55 in a ratio of ca. 4:1 whilst the 5-methoxycarbonyldodecane-4,8-dione 53 gave a 1: ca. 4 ratio.
- Cadman, Michael L. F.,Crombie, Leslie,Freeman, Stephen,Mistry, Jayshree
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p. 1397 - 1408
(2007/10/02)
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- A Systematic Study on the Bakers'Yeast Reduction of 2-Oxoalkyl Benzoates and 1-Chloro-2-alkanones
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The bakers' yeast reduction of a series of 2-oxoalkyl arenecarboxylates (1a-f) (R=CH3 to n-C6H13; X=H) and the phenyl-modified derivatives (1g-l) (R=n-C5H11, X=OH, CH3, F, Cl, Br, or I) as well as 1-chloro-2-alkanones R(C=O)CH2Cl (6a-f) (R=CH3 to n-C6H13) were systematically investigated.The substrate specificities, configuration and percentee of the reduction products were found to be highly dependent on the length of the alkyl group (R) and the α substituent.Thus, the benzoates 1a-f gave optically active 2-hydroxyalkyl benzoates (2a-f) (R, configuration, percentee) (a: CH3, S, 99; b: C2H5, S, 98; c: C3H7, S, 26; d: n-C4H9, R, 55; e: n-C5H11, S, 15; f: n-C6H13, S, 63) in 11-91percent yields.Among the modification experiments of the phenyl group, 1g-l, the p-iodo substituent markedly increased the ee from 15 to 71percent, although the yield was rather lowered (22percent yield).The reduction of α-chloro ketones 6a-f also gave optically active 1-chloro-2-alkanols (7a-f) in 16-69percent yields.
- Sakai, Takashi,Wada, Kou,Murakami, Takahiko,Kohra, Kiichiro,Imajo, Norihisa,et al.
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p. 631 - 638
(2007/10/02)
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- SYNTHESE ET ETUDE ELECTROCHIMIQUE DE POLY(ALKYL-3 SELENOPHENES)
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Synthesis of 3-alkyl selenophenes via chloromethyl ketones and acetylenic chlorhydrins is described.The electropolymerisation yields electroactive and soluble polymers with high conductivity in the doped state.
- Mahatsekake, C.,Catel, J. M.,Andrieu, C. G.,Ebel, M.,Mollier, Y.,Tourillon, G.
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- Piperazines 1-hexyl-4(3-ketohexyl)
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Substituted piperazines of the following formula STR1 wherein R1 is C3 -C7 alkyl; R2 is keto or hydroxy C3 -C7 alkyl, keto C4 -C8 cycloakyl, C4 -C8/su
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- Addition of 4-Chlorobenzenesulphenyl Chloride to 3-Methylbut-1-yne, Hex-1-yne, and Phenylacetylene: Isomerisation and Hydrolysis of the Adducts
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The addition of (4-ClC6H4SCl, (2), to RCH(*)CH, (1; R=Pri, Bun), gives (E)-4-ClC6H4(R)C(*)C(H)Cl, (E)-(3), and (E)-4-ClC6H4(H)C(*)C(R)Cl, (E)-(4) in a fixed ratio; the addition to (1; R=Ph) gives regiospecifically (E)-(3; R=Ph) in ethyl acetate, but different proportions of (E)-(3) and (E)-(4) (R=Ph), in chloroform, sym-tetrachloroethane, and acetic acid.With an excess of the sulphenyl chloride (2), (E)-(3) and (E)-(4) isomerize to (Z)-(4) (same R).The sulphuric-acid catalysed hydrolysis of (E)-(3; R=Pri, Bun, Ph) gives α-chloroketones RCOCH2Cl(5) (same R).The (E)-(4) isomers do not hydrolyse.
- Capozzi, Giuseppe,Romeo, Giovanni,Lucchini, Vittorio,Modena, Giorgio
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p. 831 - 836
(2007/10/02)
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- 1-Hydroxymethyl-1-oxo-prostane-derivatives of the E, A and F-series
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The invention disclosed herein relates to pharmacologically active prostaglandin derivatives of the E, F, or A series having on the terminal methylene carbon of the alpha chain a substituent selected from the group consisting of: STR1 wherein R is an alkyl group and R15 is C1 -C4 alkyl, di-C1 -C4 -alkylamino, C1 -C4 alkoxy, and phenyl or phenyl substituted with one or more substituents from the group consisting of C1 -C4, OR, SR, F, or Cl wherein R is as previously defined.
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- 1-Substituted-1-oxo-prostane-derivatives of the E, A and F series
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The invention disclosed herein relates to pharmacologically active prostaglandin derivatives of the E, F, or A series having on the terminal methylene carbon of the alpha chain, a substituent selected from the group consisting of: STR1 wherein R is C1 to C6 alkyl, and phenyl or phenyl substituted with one or more substituents selected from the group consisting of C1 -C4 alkyl, OR16, SR16, F, or Cl, and R16 is C1 to C6 alkyl.
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- 15-Deoxy-16-hydroxy-16-chloromethyl or bromomethyl prostaglandins of the E and F series
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The invention disclosed herein relates to pharmacologically active prostaglandins of the E and F series in which C-16 is substituted with hydroxyl and chloromethyl or bromomethyl as well as the pharmacologically acceptable, nontoxic lower alkyl esters and salts thereof, and to the intermediates and processes for producing such compounds.
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- N-(Heterocycl ic-alkyl)-9-xanthenylamines
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The compounds are N-(imidazolylalkyl, imidazolinylalkyl and tetrahydropyrimidylalkyl)-9-xanthenylamines which have gastric acid secretion inhibitory activity.
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