- Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state
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(Chemical Equation Presented) A clue to the origin of chirality? A solution of proline with high enantiomeric excess (85-99% ee) was obtained from solid proline of only 10% ee through novel dissolution and crystallization processes (see scheme). This observation may be an explanation for the origin of chirality on Earth.
- Hayashi, Yujiro,Matsuzawa, Masayoshi,Yamaguchi, Junichiro,Yonehara, Sayaka,Matsumoto, Yasunobu,Shoji, Mitsuru,Hashizume, Daisuke,Koshino, Hiroyuki
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Read Online
- Ketene Dithioacetals as 1,3-Dipolarophiles. Applications to the Synthesis of Cyclic Amino Acids
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Intramolecular azide cycloaddition reactions of ketene dithioacetals provide a new route to cyclic amino acids and a stereoselective synthesis of (2S,3S,4R)-3,4-dihydroxyproline (14) based on this methodology is described.
- Moss, William O.,Bradbury, Robert H.,Hales, Neil J.,Gallagher, Timothy
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Read Online
- Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors
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An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)2borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 μM.
- Loughlin, Wendy A.,Schweiker, Stephanie S.,Jenkins, Ian D.,Henderson, Luke C.
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p. 1576 - 1582
(2013/03/29)
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- HETEROCYCLIC COMPOUND DERIVATIVES AND MEDICINES
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The present invention provides a compound which is useful as a PGI2 receptor agonist, and a pharmaceutical composition. The present invention is directed to a pharmaceutical composition comprising a compound represented by the following formula [1]: (R1 and R2 are the same or different and each represents optionally substituted aryl, Y represents N or CH, Z represents N or CH, A represents NH, NR5, O, S, or ethylene, R5 represents alkyl, D represents alkylene or alkenylene, E represents phenylene or single bond, G represents O, S, or CH2, R3 and R4 are the same or different and each represents hydrogen or alkyl, Q represents carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, or N-(alkylsulfonyl)carbamoyl), or a pharmaceutically acceptable salt thereof as an active ingredient.
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- Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP
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For the preparation of both enantiomers of N-carbamoyl-2-methoxymethylpyrrolidine, the precursors of Enders' chiral auxiliaries, SAMP and RAMP, enzyme-catalyzed kinetic resolution of racemic N-carbamoyl, N-Boc, N-Cbz proline esters and prolinols were examined. B. licheniformis protease (subtilisin) preferentially hydrolyzed the (R)-carbamoylproline ester with an enantiomeric ratio (E) of 10. To a hydrophobic N-Cbz proline ester, subtilisin showed lower selectivity (E=2.8), and in contrast, a purified protease (isozyme A) from the earthworm showed the preference of (S)-enantiomer (E=13.6). In a practical sense, C. antarctica lipase B (Chirazyme L-2) was effective for the hydrolysis of both N-Boc and N-Cbz derivatives with E >100. The e.e. of (R)-N-carbamoyl-2-methoxymethylpyrrolidine was raised to be >99.9% by recrystallization at the N-Boc-prolinol stage, which was derived from the (R)-N-Boc-proline methyl ester (98.7% e.e.) through a preparative-scale enzyme-catalyzed resolution (49% yield) of the racemic substrate.
- Kurokawa, Masayuki,Shindo, Takeyuki,Suzuki, Masumi,Nakajima, Nobuyoshi,Ishihara, Kohji,Sugai, Takeshi
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p. 1323 - 1333
(2007/10/03)
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- Ketene-S,S-Acetals As 1,3-Dipolarophiles Towards Azides. A New Synthetic Entry Into Cyclic Amino Acids
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Intramolecular azide cycloaddition reactions of ketene-S,S-acetals proceed to give a reactive imine as the initially-formed intermediate and this mechanism is supported by thermolysis of (18) which gave the stable imine (22).N-Acylation of this intermedia
- Moss, William O.,Wakefield, Emma,Mahon, Mary F.,Molloy, Kieran C.,Bradbury, Robert H.,et al.
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p. 7551 - 7564
(2007/10/02)
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- SELECTIVE TRANSFORMATION OF N-t-BUTOXYCARBONYL GROUP INTO N-ALKOXYCARBONYL GROUP via N-CARBOXYLATE ION EQUIVALENT
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Reaction of a variety of N-t-butoxycarbonyl compounds with t-butyldimethylsilyl trifluoromethanesulfonate afforded the N-t-butyldimethylsilyloxycarbonyl compounds, chemoselectively, which upon treatment with an alkyl or aryl halide provided the corresponding N-alkoxy- or N-aryloxycarbonyl compounds, efficiently.
- Sakaitani, Masahiro,Ohfune, Yasufumi
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p. 5543 - 5546
(2007/10/02)
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