- Enantioselective inclusion of pyrene-1-sulfonate salts of α-amino acids with crystals of α-cyclodextrin
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Enantioselective inclusion of α-amino acids with crystals of α-cyclodextrin (α-CD) has been achieved by converting the amino acids into sulfonate salts with pyrene-1-sulfonic acid (PyS). For example, crystals of α-CD selectively include L-leucine/PyS (1:1) salt in a host/guest ratio of ～1 with 92%ee from a solution of the racemic salt in ethanol/N-methylformamide (91:9) at 40 °C. Under conditions optimized for individual amino acids, the PyS salts of valine, phenylalanine, and methionine are also included with good enantioselectivities (up to 86%ee). Mechanistic studies for the inclusion of leucine/PyS salt reveals that the enantioselectivity originates from the difference in stability between the inclusion complexes of D- and L-leucine/PyS salts with α-CD in crystals.
- Hattori, Tetsutaro,Kitamoto, Yuichi,Maeda, Tetsuya,Miyoshi, Ikuko,Morohashi, Naoya
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- Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
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Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
- King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
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supporting information; experimental part
p. 4815 - 4830
(2011/10/01)
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- Resolution of non-proteinogenic amino acids via microbial lipase-catalyzed enantioselective transesterification
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A number of non-proteinogenic amino acids bearing aliphatic side chains were resolved with moderate to good enantioselectivities (E = 15-42) through the Burkholderia cepacia lipase-catalyzed enantioselective transesterification of the 2,2,2-trifluoroethyl esters of their N-benzyloxycarbonyl derivatives with methanol as a nucleophile in diisopropyl ether.
- Miyazawa, Toshifumi,Mio, Motoe,Watanabe, Yuko,Yamada, Takashi
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p. 219 - 224
(2008/09/20)
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- The total synthesis of pamamycin-607. Part 2: Synthesis of the C6-C18 domain
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Synthesis of the C6-C18 domain of pamamycin-607 was achieved in ten steps and 7% overall yield from commercially available d-norvaline. The key asymmetric transformations included a Paterson anti aldol addition, an anti selective reduction of the resultan
- Fraser, Benjamin H.,Mulder, Roger J.,Perlmutter, Patrick
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p. 2857 - 2867
(2007/10/03)
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- Enantioselective synthesis and absolute configuration of (-)-1-(benzofuran-2-yl)-2-propylaminopentane, ((-)-BPAP), a highly potent and selective catecholaminergic activity enhancer
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Enantioselective synthesis and absolute configuration of (-)-1-(benzofuran-2-yl)-2-propylaminopentane ((-)-BPAP), which is a highly potent and selective catecholaminergic activity enhancer (CAE) substance, are described. The synthetic approach consists of the coupling reaction of benzofuran with (R)-N-tosyl-2-propylazirizine or (R)-N-methoxy-N-methylnorvaliamide, followed by appropriate modifications of the resulting coupling products. As the results, (-)-BPAP turned out to have the R configuration, which was finally confirmed by X-ray crystallographic analysis.
- Oka, Takahiro,Yasusa, Takuya,Ando, Takashi,Watanabe, Mayumi,Yoneda, Fumio,Ishida, Toshimasa,Knoll, Joseph
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p. 1213 - 1219
(2007/10/03)
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- Structure-Activity Study of 5-Substituted 1-Carbobenzoxy-2-iminohydantoins as Potential Anticonvulsant Agents
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On the basis of our previous findings, a series of 5-substituted 2-iminohydantoins has been synthesized and tested for anticonvulsant activity to better understand the SAR of 2-iminohydantoins.Among the compounds tested, (S)-(+)-1-carbobenzoxy-2-iminohydantoin analogs with ethyl (6)-, n-propyl (7a)-, isopropyl (8)-, allyl (9)-, and sec-butyl (11)-substituted groups at the C5 of the iminohydanotin ring provided the best activities against the MES test with ED50 values in the range of 52-74 mg/kg.All of the above compounds except 8 also showed activity against the scMET test with ED50 values in the range of 141-223 mg/kg.All significantly active compounds (1, 6, 7a, 8, 9, and 11) possesed aliphatic hydrocarbon side chains of two- to three-carbon lengths at the C5 position.All of the compounds with no or minimal activity had either shorter or longer side chains.The compounds substituted at the C5 position by aryl groups, arylalkyl groups, or alkyl and arylalkyl groups containing heteroatoms also showed no activity against the MES and scMET tests.The results suggested that the C5 side chain with the correct stereochemistry in 2-iminohydantoins provides optimal anticonvulsant activity when the side chains are aliphatic hydrocarbons with a lenght, ignoring branchingg, of two to three carbons.
- Sun, Zhong-Yue,Kwon, Chul-Hoon,Wurpel, John N. D.
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p. 2841 - 2845
(2007/10/02)
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- Porcine Pancreatic Lipase Catalyzed Enantioselective Hydrolysis of Esters of N-Protected Unusual Amino Acids
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Porcine pancreatic lipase catalyzed the highly enantioselective hydrolysis of a kind of α-substituted carboxylic esters, i.e., the 2,2,2-trifluoroethyl esters of the N-benzyloxycarbonyl derivatives of unusual amino acids.
- Miyazawa, Toshifumi,Iwanaga, Hitoshi,Ueji, Shinichi,Yamada,Takashi,Kuwata, Shigeru
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p. 2219 - 2222
(2007/10/02)
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- Optical Resolution of Unusual Amino-Acids by Lipase-catalysed Hydrolysis
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The 2-chloroethyl esters of the N-benzyloxycarbonyl (Z) derivatives of several unusual amino-acids are converted by Aspergillus niger lipase into enantiomerically enriched Z-amino-acids with fairly high optical purities, the L-enantiomers being preferentially hydrolysed.
- Miyazawa, Toshifumi,Takitani, Tadanori,Ueji, Shinichi,Yamada, Takashi,Kuwata, Shigeru
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p. 1214 - 1216
(2007/10/02)
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- PAPAIN-ASSISTED RESOLUTION OF NATURAL AND XENOBIOTIC α-AMINO ACIDS
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A new and convenient method for the preparation of pure enantiomers of α-amino acids is described.Industrial papain, catalyzes the synthesis of L-Z-amino acid ethyl esters in ethanolic medium, with good yields.These esters are obtained from DL-Z-amino acids with 100percent optical purity.Unreactive D-Z-amino acids are readily isolated from reaction medium.Physical constants of natural and xenobiotic L-Z-amino acid esters and D-Z-amino acids are described.
- Moriniere, J. L.,Danree, B.,Lemoine, J.,Guy, A.
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p. 441 - 444
(2007/10/02)
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- Nonapeptide amide analogs of luteinizing releasing hormone
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The novel nonapeptide amide derivatives of the formula wherein R1 is Tyr or Phe; R2 is D-Leu, D-Ile, D-Nle, D-Val, D-NVa, D-Abu, α-Aibu, D-Phe, D-Phg, D-Ser, D-Thr or D-Met; R3 is Leu, Ile or Nle and R4 is alkyl
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