D-GLUCONHYDROXIMO-1,5-LACTAM AND RELATED N-ARYLCARBAMATES - THEORETICAL CALCULATIONS, STRUCTURE, SYNTHESIS, AND INHIBITORY EFFECT ON BETA-GLUCOSIDASES

被引:60
作者
HOOS, R
NAUGHTON, AB
THIEL, W
VASELLA, A
WEBER, W
RUPITZ, K
WITHERS, SG
机构
[1] UNIV ZURICH,INST ORGAN CHEM,CH-8057 ZURICH,SWITZERLAND
[2] UNIV BRITISH COLUMBIA,DEPT CHEM,VANCOUVER V6T 1Z1,BC,CANADA
关键词
D O I
10.1002/hlca.19930760723
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The known D-gluconhydroximo-1,5-lactam (= D-glucono- 1,5-lactam oxime) 7a, its nitrogen isotopomers 7b and 7c, and the N-arylcarbamates 26-29 were synthesized from 2,3,4,6-tetra-0-benzyl-D-glucono-1,5-lactam (11a) and its nitrogen isotopomer 11b to establish the controversial structure of 7a and to study the inhibition of beta-glucosidases by the N-arylcarbamates 26-29. Conversion of 11a with Lawesson's reagent yielded a mixture of the thionolactam 15a and its manno-configurated isomer 16a, which was transformed into a mixture of the benzylated hydroximo-lactam 13a and the manno-isomer 17a. Debenzylation (Na/NH3) and acetylation of this mixture led to the gluco-configurated pentaacetate 14a and the manno-isomer 18a. Treatment of 11a with Et3O-BF4 and then with H2NOH gave exclusively the benzylated D-gluconhydroximo-1,5-lactam (benzylated D-nojirilactam oxime) 13a, which was transformed into 14a. Deacetylation of 14a yielded the hydroximo-lactam 7a. The isotopomers 7b and 7c were obtained by analogous reaction sequences, using either (NH3)-N-15 or (NH2OH)-N-15.HCl. To prepare the acetylated N-arylcarbamates 20-25, 13a was debenzylated and acetylated (--> 14a), followed by selective deacetylation to the tetraacetate 19a and treatment with the appropriate isocyanates. The structure of the 2-chlorophenyl carbamate 21 was established by X-ray analysis. Deacetylation of 20-23 led to the N-arylcarbamates 26-29. The N-15-NMR spectra of 7b, 7c, and of their precursors 13b, 13c, 14b, and 14c, show that the C=N bond in all these lactam oximes is exocyclic as predicted from semiempirical and ab initio SCF-MO calculations on the structure of acetamide oxime and 5-pentanelactam oxime. According to these calculations, 5-pentanelactam oxime is a (Z)-configurated, flattened chair. X-ray analysis established the structure Of D-glucono-1,5-lactam oxime (7a) in the solid state, where it adopts a conformation between C-4(1) and H-4(3). In H2O, 7a is a flattened C-4(1). The calculations also predict that protonation at the exocyclic N-atom strengthens the conjugation between the endocyclic N-atom and the hydroxyimino group, and leads to a half-chair conformation. This is evidenced by the chemical shift differences in the N-15-NMR spectra observed upon protonation of 7b and 7c. The hydroximolactam 7a and the N-arylcarbamates 26-29 are competitive inhibitors of the beta-glucosidases from sweet almond (emulsin) and from Agrobacterium faecalis (= Abg), with K(I) values between 8 and 21 . 10(-6) m against emulsin (at pH 6.8) and between 0.15 and 1.2-10(-6) m against Abg (at pH 7.0).
引用
收藏
页码:2666 / 2686
页数:21
相关论文
共 38 条
[1]   NITROSOMETHANE AND ITS NITRONE AND OXIME ISOMERS - A THEORETICAL-STUDY OF 1,2-INTRAMOLECULAR AND 1,3-INTRAMOLECULAR HYDROGEN SHIFTS [J].
ADENEY, PD ;
BOUMA, WJ ;
RADOM, L ;
RODWELL, WR .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (12) :4069-4074
[2]  
AEBISCHER BM, 1983, THESIS U FREIBURG
[3]  
[Anonymous], 1986, AB INITIO MOL ORBITA
[4]   ALPHA-LITHIOAMINE SYNTHETIC EQUIVALENTS - SYNTHESES OF DIASTEREOISOMERS FROM THE BOC PIPERIDINES [J].
BEAK, P ;
LEE, WK .
JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (09) :2578-2580
[5]   INHIBITION OF EMULSION BY D-GLUCONHYDROXIMO-1,5-LACTONE AND RELATED-COMPOUNDS [J].
BEER, D ;
VASELLA, A .
HELVETICA CHIMICA ACTA, 1986, 69 (02) :267-270
[6]   NITROGEN-15 MAGNETIC RESONANCE SPECTROSCOPY .2. COUPLING CONSTANTS [J].
BINSCH, G ;
ROBERTS, JD ;
ROBERTS, BW ;
LAMBERT, JB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (24) :5564-&
[7]   N-15 NMR-STUDIES OF 2-HYDROXYGUANIDINES AND AMIDE OXIMES [J].
CLEMENT, B ;
KAMPCHEN, T .
CHEMISCHE BERICHTE-RECUEIL, 1985, 118 (09) :3481-3491
[8]   REVERSIBLE INHIBITORS OF BETA-GLUCOSIDASE [J].
DALE, MP ;
ENSLEY, HE ;
KERN, K ;
SASTRY, KAR ;
BYERS, LD .
BIOCHEMISTRY, 1985, 24 (14) :3530-3539
[9]   EVALUATION OF AM1 CALCULATED PROTON AFFINITIES AND DEPROTONATION ENTHALPIES [J].
DEWAR, MJS ;
DIETER, KM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1986, 108 (25) :8075-8086
[10]   THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].
DEWAR, MJS ;
ZOEBISCH, EG ;
HEALY, EF ;
STEWART, JJP .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909