ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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-O-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 β-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 15NH3 or 15NH2OHHCl. 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 15N-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 4C1 and 4H3. In H2O, 7a is a flattened 4C1. 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 15N-NMR spectra observed upon protonation of 7b and 7c. The hydroximolactam 7a and the N-arylcarbamates 26-29 are competitive inhibitors of the β-glucosidases from sweet almond (emulsin) and from Agrobacterium faecalis (= Abg), with KI values between 8 and 21·10-6M against emulsin (at pH 6.8) and between 0.15 and 1.2·10-6M against Abg (at pH 7.0).
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19930760723
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