Studies on Optically Active Amino Acids. V. Synthesis of Optically Active α-Aminoalcohols by the Reduction of α-Amino Acid Esters with Sodium Borohydride

Seki, Hedeo; Koga, Kenji; Matsuo, Hisayuki; Ohki, Sadao; Matsuo, Ichiro; Yamada, Shunichi

doi:10.1248/cpb.13.995

Cited by 88 publications

(24 citation statements)

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“…Boc-MePhe-OH [48] (3.1 g, 11 mmol) and N-ethyl-morpholine (1.4 ml, 11 mmol) were dissolved in tetrahydrofuran (30 ml) and cooled to -20". Isobutyl chloroformate (1.45 ml, 11 mmol) was added followed, after stirring at -15" for 10 min, by a cold solution of L-methioninol [49] (1.8 g, 13.3 mmol) in THF (10 ml). After stirring at -5" for 3 h and at 20" for 1 h, the mixture was diluted with ethyl acetate (170 ml) and ether (170 ml) and extracted with several portions of water, 2~ citric acid, IM KHC03 and 30% NaC1-solution.…”

Section: Metmentioning

confidence: 99%

Synthesis, Opiate Receptor Binding and Analgesic Activity of Enkephalin Analogues

Pless¹,

Bauer²,

Cardinaux³

et al. 1979

Helvetica Chimica Acta

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SummaryThe synthesis and biological testing of analogues of Met-enkephalin, a recently discovered opioid peptide from mammalian brain, are described. Testing involved determination of affinity constants for an opiate receptor site and of analgesic potency in the tail-flick test in mouse. The effects on opioid activity of modifying various parts of the enkephalin molecule are discussed. Tyr-D-Ala-Gly-MePheMet (O)-oll) (FK 33-824), which was highly active in these tests, was subsequently selected for clinical testing.The use of two complementary models -in vitro binding studies and in vivo test for analgesia -for the assessment of biological activity in the evaluation of analogues is explained.

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Section: Metmentioning

confidence: 99%

Synthesis, Opiate Receptor Binding and Analgesic Activity of Enkephalin Analogues

Pless¹,

Bauer²,

Cardinaux³

et al. 1979

Helvetica Chimica Acta

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“…Infrared: 1680 cm-I; 'Hmr 6: 1.19 (s,9),1.96(d,1,J = 3.51,2.35(d,1,J = 5.0),2),l),7.2(s,5);[aIDz4 96.2(c2.30);Anal. calcd.…”

Section: (+)-L-(piualoyl)-2(s)-benzylaziridinementioning

confidence: 99%

A mild, general preparation of N-acyl aziridines and 2-substituted 4(S)-benzyloxazolines

Bates¹,

Varelas²

1980

Can. J. Chem.

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“…L-Phenyl alanine -33.6' (c 1.54, HzO) was converted into S-(-)-2-amino-3-phenylpropan-1-01 ([a], ) according to the procedure of Seki et al (5). Ditosylation of this aminoalcohol according to the procedure outlined above for 2-aminoethanol gave an 83% yield of the chiral ditosylate, mp 100-101.5"C (EtOAc-hexane); ir: 3600, lm, 1370, 1170, 1150, 1090IHmr 6 : 2.35 2.40(s33),2.70(m.%), 3.55(m, 1),3.90(.n,2), 5.25(d, 1,9= 8), 6.8-7.8 (m, 13); [a], CMC1,).…”

Section: N-(gto!uenesr~lphony[1-2s(benzyl)aziridine Imentioning

confidence: 99%

Dianions of glyoxylic acid thioketals: conventent α-keto acid equivalents

Bates¹,

Ramaswamy²

1980

Can. J. Chem.

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. Can. J. Chem. 58,716 (1980). By varying the solvent, reaction temperature, and bases (i.e., gegenions present), optimum conditions for the alkylation of the dianions of glyoxylic acid derivatives 8 and 9 were established. It was found that the easily prepared, thermally stable, tetrahydrofuran-soluble potassium dianion of bis(ethy1thio)acetic acid was readily alkylated by alkyl halides. tosylates, epoxides, and N-tosyl aziridines. The latter alkylation is being used to develop a possible cytochalasin synthesis.The alkylated products may be readily converted into the corresponding a-keto acids or methyl 2,2-bismethoxycarboxylates. Chem. 58,716 (1980). On a etabli des conditions ideales d'alkylation des dianions de derives 8 et 9 de l'acide glyoxylique en faisant varier le solvant, la temperature et les bases (i.e., ions opposes). On a trouve que le dianion de potassium de l'acide bis(ethylthi0) acetique, soluble dans le tetrahydrofuranne que l'on peut preparer facilement et qui est thermiquement stable, peut &re alkyle facilement par les halogenures d'alkyles, les tosylates, les epoxydes et les N-tosyl-aziridines. On utilise la derniere alkylation pour developper une synthese realisable de la cytochalasine. Les produits alkyles peuvent etre transformes facilement en acides u cetoniques correspondants ou en carboxylates de bismethoxy-2,2 de methyle.[Traduit par le journal]In connection with a preliminary investigation directed at a synthesis of the microbial metabolites cytochalasins A, B, and F (1, 2)2 we required a glyoxylic acid (ester) anion equivalent (3).3 Our strategy involves alkylation of such an anion with an aziridine unit 1 which incorporates the chirality at C-3 of the cytochalasins, eventually followed by lactam formation to give compound 2. This inter-mediate contains an oxygen function at what will eventually become the C-9 position of the target molecules, and thus overcomes a possible difficulty arising from attempted oxidation at this hindered position later in the synthesis (2g). Cleavage of the aziridine by a nucleophile will result in a developing negative charge on the nitrogen atom. To facilitate the opening of the aziridine, the group R1 (attached to nitrogen) should thus be capable of stabilizing this negative charge, and in addition should not itself be very susceptible to nucleophilic attack. Thep-toluenesulphonyl group appeared to fulfil the necessary criteria (4).4 L-Phenylalanine was converted to the corresponding chiral amino alcohol ( 5 ) , which was subsequently ditosylated and cyclized to the desired crystalline chiral aziridine derivative B (R' = p-MeC,H,SO,-) which was used in our subsequent studies.The glyoxylic acid (ester) anion equivalent should possess a number of characteristics: ready availability, ease of preparation, high reactivity, and thermal stability. In addition, alkylation of this synthon should proceed in high yield to give a product which is stable and easily puj-ified and yet is readily convertible into the desired a-keto acid (ester). An investigation of t...

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Studies on Optically Active Amino Acids. V. Synthesis of Optically Active α-Aminoalcohols by the Reduction of α-Amino Acid Esters with Sodium Borohydride

Cited by 88 publications

References 0 publications

Synthesis, Opiate Receptor Binding and Analgesic Activity of Enkephalin Analogues

Synthesis, Opiate Receptor Binding and Analgesic Activity of Enkephalin Analogues

A mild, general preparation of N-acyl aziridines and 2-substituted 4(S)-benzyloxazolines

Dianions of glyoxylic acid thioketals: conventent α-keto acid equivalents

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