- Novel μ opioid antagonists derived from the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2)
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Hybrid analogues of the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2, Dmt?=?2′,6′-dimethyltyrosine) containing cis-4-amino-Pro, trans-4-amino-Pro, cis-4-aminoethyl-Pro or cis-4-guanidinylethyl-Pro in the 2 p
- Shi, Saijian,Xu, Jian,Feng, LingLing,Fan, Xin,Chen, Zhen,Qin, Yajuan,Chung, Nga N.,Li, Tingyou,Schiller, Peter W.
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p. 1305 - 1314
(2020/08/05)
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- DIMERIC PEPTIDE INHIBITORS OF APOPTOSIS PROTEINS
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The present technology is directed to compounds, compositions, and methods related to treatment of cancers and viral infections mediated by lAPs. In particular the present compounds and compositions may be used to treat lAP-mediated ovarian cancer and hepatitis B infection.
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Paragraph 0156
(2019/02/13)
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- Production of cis-4-hydroxyproline
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PROBLEM TO BE SOLVED: To produce cis-4-hydroxyproline useful as a raw material of medicines and agrochemicals by an industrially suitable method.SOLUTION: The method for producing cis-4-hydroxyproline includes: hydrolyzing a hydroxyproline derivative represented by formula (1), wherein Rdenotes a 1-6C alkylcarbonyl group, an arylcarbonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aralkyloxycarbonyl group, in the presence of a hydrochloric acid catalyst; neutralizing the resultant with an organic base; and thereafter diluting the resultant with an alcohol.
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- Synthesis of (2S,4S)-4-hydroxyproline from D-glucose
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Diacetone-D-glucose 1 gives 3-O-methylxanthate 2 on reaction with NaH=Me I. Reductive deoxygenation of compound 2 by Bu3SnH gives the corresponding 3-deoxy glucose derivative 3 and on acid-catalyzed regioselective deprotection of C-5,6-acetonide gives the diol 4. The diol on oxidative cleavage with NaIO4 gives the aldehyde 5, which on further condensation with benzylamine followed by reduction with NaBH4 gives the amine 7. Z-Protection of the amine followed by methanolysis gives methyl furanoside 9. Reaction of 9 with methanesulfonyl chloride=Et3N gives the corresponding C-3-O-mesylate derivative 10. Catalytic hydrogenation of compound 10 (Pd=C=H2=MeOH 3 kg) gives bicyclic oxaazo compound 11, due to deprotection of the N-benzyl- and Z-protecting groups and intramolecular nucleophilic displacement of the C-2-O-mesylate by the C-5 amine in a one-pot reaction. Z-Protection of the amine 11 followed by acid-catalyzed hydrolysis gives acetal 13. Reduction of acetal by use of NaBH4 gives Z-prolinol 14. Selective oxidation of diol 14 by (2,2,6,6-tetramethylpiperidin-1-yl)-oxyl (TEMPO)=[(bis)(acetoxy)iodo]-benzene (BAIB) and NaClO2=NaH 2PO4, followed by Z-deprotection, gives the title compound I in 3.5% overall yield from D-glucose. Copyright Taylor & Francis Group, LLC.
- Mereyala, Hari Babu,Pathuri, Gopal,Nagarapu, Lingaiah
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p. 1278 - 1287
(2012/04/17)
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- SYNTHESIS OF PYRROLIDINE COMPOUNDS
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Provided are methods for the preparation of certain substituted pyrrolidine compounds, forms of (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride, and methods for preparing and using these forms.
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Page/Page column 69-71
(2008/12/07)
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- METHOD FOR PREPARING (CIS)-4-HYDROXYPROLINE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a method for preparing a (cis)-4-hydroxyproline derivative by a simple operation. SOLUTION: The (cis)-4-hydroxyproline derivative useful as an intermediate for drugs can be prepared in a good yield by a simple operation by adding a basic compound on the hydrolysis of a (trans)-4-hydroxyproline ester derivative to perform the reaction at a high temperature (50-120°C), and thereafter lowering the temperature of the reaction solution to 0-40°C to add the basic compound again.
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Page/Page column 8
(2008/06/13)
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- Method of inhibiting the transport of L-glutamate to treat CNS disorders
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A method of inhibiting the transport of a neurotransmitter away from the synapse comprising contacting a neurotransmitter transporter with a compound having the structure STR1 wherein STR2 or CONHR 3 in any combination and and wherein R 2 =OR 3, NR 3 2, alkyl, or substituted alkyl and R 3 =alkyl or substituted alkyl.
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- Regioselective synthesis of nitrones by decarboxylative oxidation of N- alkyl-α-amino acids and application to the synthesis of 1-azabicyclic alkaloids
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Tungstate-catalyzed oxidation of N-alkyl-2a-amino acids with 30% H2O2 solution under phase-transfer conditions gives nitrones regioselectively in good yields: Using this method, stereodivergent synthesis of (R)- and (S)-4- (t-butyldimethylsilyloxy)-1-pyrroline N-oxides ((R)-17a and (S)-17a) was achieved. In addition, (R)- and (S)-3-(t-butyldimethylsilyloxy)-1-pyrroline N-oxides ((R)-45 and (S)-45) were prepared by catalytic oxidation of the corresponding chiral pyrrolidines in a regioselective manner. These chiral cyclic nitrones, 17 and 45 are versatile intermediates for the synthesis of optically active nitrogen heterocycles, since stereoselective additions of carbon nucleophiles to these chiral nitrones can be readily performed. Typically, ZnI2-mediated addition of ketene t-butyldimethylsilyi methyl acetal (29a): to (R)-17a gave the' cis-adduct, methyl (2R,4R)-[1,4-bis(t- butyldimethylsilyloxy)pyrrolidin-2-yl]acetate (cis-30). In contrast, the addition of lithium acetylides 34 to the nitrone (R)-17a gave the trans- adducts, (2S,4R)-2-(1-alkynyl)-4-(t-butyldimethylsilyloxy)-1- hydroxypyrrolidines trans-35. These adducts are useful intermediates for syntheses of the nitrogen heterocycles (3R,5R)-1-aza-3- hydroxybicyclo[3.3.0]octane (37) and (6R,8R)-1-aza-8- hydroxybicyclo[4.30]nonane (38), respectively. The ZnI2-mediated addition of ketene silyl acetal 29a to the nitrone (R)-45 gave methyl (2S, 3R)-[1,3- bis(t-butyldimethylsilyloxy)pyrrolidin-2-yl]acetate (trans-50a), which was used for asymmetric synthesis of the Geissman-Waiss lactone ((-)-49).
- Ohtake, Hiroaki,Imada, Yasushi,Murahashi, Shun-Ichi
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p. 2737 - 2754
(2007/10/03)
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- Sialyl Lewis X mimetics incorporating fucopeptides
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Sialyl Lewis X mimetics incorporating fucopeptides are synthesized and shown to mimic the configuration and essential functional groups of sialyl Lewis X in space. The fucopeptides exhibit substantially the same biological activity as sialyl Lewis X in th
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- Nucleosides and Oligonucleotides Derived from trans-4-Hydroxy-N-acetylprolinol
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The 4-O-phosphoramidites of monomethoxytritylated 4-hydroxy-N-6-benzoyladenin-9-yl)acetyl>prolinol and 4-hydroxy-N-prolinol were prepared for incorporation into nucleic acids.The L-trans all-adenine oligonucleotide (ON) hybridises to natural oligothymidylate, apparently via triplex formation.All-purine sequences of the L-trans form can also form homo-complexes with their pyrimidine counterpart.The D-trans compounds give larger destabilisation when inserted in DNA.D-trans all-adenine ONs do not form complexes with natural oligothymidylate.For this series of modified ONs no hybridisation could be detected between complementary strands of opposite enantiomeric form.
- Ceulemans, G.,Aerschot, A. Van,Herdewijn, P.
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p. S234 - S237
(2007/10/03)
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- A Convenient Synthesis of (2S,4S)-4-Hydroxyproline
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A practical synthesis of (2S,4S)-4-hydroxyproline (1) based on DCC-induced inversion of the hydroxyl group of (2S,4R)-4-hydroxyproline (2) is described.
- Seki, Masahiko,Matsumoto, Kazuo
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p. 1161 - 1162
(2007/10/02)
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- Synthesis of De(hydroxymethyl)desulfo Analogues of Bulgecins A, B and C
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The syntheses of de(hydroxymethyl)desulfo analogues of Bulgecin A, B and C are described.Stereospecific β-glycosylation of aglycones was achieved using Schmidt's trichloroacetimidate metodology.
- Brown, Allan G.,Moss, Stephen F.,Southgate, Robert
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p. 451 - 454
(2007/10/02)
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- A synthesis of indolizidines related to castanospermine and swainsonine
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A general synthetic route to indolizidine alkaloids which are structurally similar to castanospermine and swainsosine is described. The described route uses modified pentose sugars and chiral reagents to control the absolute configuration at each asymmetr
- Jirousek,Cheung,Babine,Sass,Schow,Wick
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p. 3671 - 3674
(2007/10/02)
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- Benzamide derivatives
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A benzamide derivative represented by the formula: STR1 having a promoting activity of gastrointestinal tract and pharmacentical composition containing the same.
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- Conformationally Defined Neurotransmitter Analogues. Selective Inhibition of Glutamate Uptake by One Pyrrolidine-2,4-dicarboxylate Diastereomer
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In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared.These "conformer mimics", the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of -L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites.While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport.These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.
- Bridges, Richard J.,Stanley, Mark S.,Anderson, Michael W.,Cotman, Carl W.,Chamberlin, A. Richard
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p. 717 - 725
(2007/10/02)
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