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Volumn 20, Issue 24, 2009, Pages 2823-2834

Proteases screening for the kinetic resolution of amines with N-acyl α-amino acid trifluoromethyl esters: automated docking approach of binding energies using Subtilisin Novo as a prototype for serine proteases

Author keywords

[No Author keywords available]

Indexed keywords

ESTER DERIVATIVE; N (9 PHENYL)NONANOYL GLYCINE TRIFLUOROETHYL ESTER; N ACETYL PHENYLALANINE TRIFLUOROETHYL ESTER; N ACYL ALPHA AMINO ACID TRIFLUOROMETHYL ESTER DERIVATIVE; N OCTANOYL ALANINE TRIFLUOROETHYL ESTER; N OCTANOYL PHENYLALANINE TRIFLUOROETHYL ESTER; N PHENYL GLYCINE TRIFLUOROETHYL ESTER; SERINE PROTEINASE; UNCLASSIFIED DRUG;

EID: 74349126447     PISSN: 09574166     EISSN: 1362511X     Source Type: Journal    
DOI: 10.1016/j.tetasy.2009.11.013     Document Type: Article
Times cited : (9)

References (51)
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    • The use of N-protected amino acid carbamoylesters as acyl donors was also shown to accelerate the rate the α-CT-catalyzed amidation of chiral amines. See:
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    • note
    • For each acyl donor conversion was monitored by GC and HPLC. No significant incidence of conversion rate on the calculated E-value was noticed.
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    • note
    • With donor 3a, 5% conversion was detected in 2 h (14% in 5 h) for the non catalyzed reaction performed in 3-methyl-3-pentanol at 21 °C at 0.5 M concentration. With donor 3d, under the same experimental conditions 2% conversion was registered in 2 h (4% in 5 h). With donor 3f, the conversion was 2% in 2 h (15% in 5 h).
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    • note
    • Only the natural (S)-enantiomer substrate was recognized by the enzyme. The resolution performed over 90 min with 2 equiv of racemic acyl donor, instead of 1 equiv (cf. Table 2, entry 8), led to the following results: amine ee (50.1%); 2f de (97.0%), C (34.1%), E (102). The ee of the remaining donor was 22.8%.
  • 41
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    • note
    • 2 failed due to the importance of non-catalyzed reaction.
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    • See: the website at
    • See: the website at http://dasher.wustl.edu/tinker.
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    • ampac 8, 1992-2004 Semichem, Inc. PO Box 1649, Shawnee, ks 66222.
    • ampac 8, 1992-2004 Semichem, Inc. PO Box 1649, Shawnee, ks 66222.


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