“…Hydrolysis of the methyl glycosides with H 2 SO 4 in AcOH/H 2 O gave the hemiacetal ( 14 ), which was oxidized with CrO 3 /pyridine, affording the lactone ( 15 ). Staudinger reduction of 15 occurred with spontaneous cyclization to afford the desired lactam ( 9 ) 2 Protonation trajectories of the glucosidic bond in the catalytic hydrolysis mechanism proposed by Heightman and Vasella: 32 (a) anti-protonation and (b) syn-protonation. 1 …”
The synthesis of xylobiose-derived nitrogen-containing inhibitors of xylanase is described starting with accessible precursors through efficient synthetic schemes. Four disaccharides were identified as powerful competitive inhibitors of the retaining family 10 xylanase, Cex, from Cellulomonas fimi, namely imidazole (K i ) 150 nM), lactam oxime (K i ) 370 nM), isofagomine (K i ) 130 nM), and deoxynojirimycin (K i ) 5800 nM) derivatives of xylobiose. By contrast, none of the compounds inhibited the family 11 xylanase, Bcx, from Bacillus circulans, to an appreciable extent. Two possible explanations are provided for the discrimination exhibited by the imidazole and the lactam oxime. One explanation relates to the different active site locations of the acid/base residue in the two enzymes: anti to the C1-O5 bond for the family 10 Cex and syn for the family 11 Bcx. The other explanation concerns proposed differences in the transition state conformation for the two enzymes: half-chair for Cex and boat for Bcx. The reasons for the difference in inhibition values between Cex and Bcx for the isofagomine and deoxynojirimycin derivatives are less clear-cut but may be ascribed to destabilizing steric and electrostatic interactions between the inhibitors and an essential tyrosine residue in the active site of Bcx.
“…Hydrolysis of the methyl glycosides with H 2 SO 4 in AcOH/H 2 O gave the hemiacetal ( 14 ), which was oxidized with CrO 3 /pyridine, affording the lactone ( 15 ). Staudinger reduction of 15 occurred with spontaneous cyclization to afford the desired lactam ( 9 ) 2 Protonation trajectories of the glucosidic bond in the catalytic hydrolysis mechanism proposed by Heightman and Vasella: 32 (a) anti-protonation and (b) syn-protonation. 1 …”
The synthesis of xylobiose-derived nitrogen-containing inhibitors of xylanase is described starting with accessible precursors through efficient synthetic schemes. Four disaccharides were identified as powerful competitive inhibitors of the retaining family 10 xylanase, Cex, from Cellulomonas fimi, namely imidazole (K i ) 150 nM), lactam oxime (K i ) 370 nM), isofagomine (K i ) 130 nM), and deoxynojirimycin (K i ) 5800 nM) derivatives of xylobiose. By contrast, none of the compounds inhibited the family 11 xylanase, Bcx, from Bacillus circulans, to an appreciable extent. Two possible explanations are provided for the discrimination exhibited by the imidazole and the lactam oxime. One explanation relates to the different active site locations of the acid/base residue in the two enzymes: anti to the C1-O5 bond for the family 10 Cex and syn for the family 11 Bcx. The other explanation concerns proposed differences in the transition state conformation for the two enzymes: half-chair for Cex and boat for Bcx. The reasons for the difference in inhibition values between Cex and Bcx for the isofagomine and deoxynojirimycin derivatives are less clear-cut but may be ascribed to destabilizing steric and electrostatic interactions between the inhibitors and an essential tyrosine residue in the active site of Bcx.
“…(Isolation of highly pure 13 is vital to the success of the subsequent palladium-catalyzed hydrogenation.) Attempts to perform this step from the crude azide as reported [20] were unseccessful in our hands. Finally, the sugar lactam 14 was treated with either methyl iodide or benzyl chloride to afford the fully N-and O-protected d-ribono-1,5-lactams 15 a and 15 b in overall yields of 52 % (15 a) and 44 % (15 b) (Scheme 4).…”
The iminoglycosylidene complexes 3 a,b, 9, and 16 a,b are conveniently prepared from the sugar lactams 2 a,b, 8, and 15 a,b by reaction with K 2 Cr(CO) 5 and subsequent deoxygenation with trimethylsilyl chloride (TMSCl). The Cr(CO) 5 -stabilized carbene moiety of the imino-d-ribo-pyranosylidene complexes 9 and 16 a,b has been exploited in the photoinduced generation of ketene-like species on irradiation with UV light. These intermediates were trapped with methanol to produce the methyl 2,6-imino-d-allonates 10 and 17 a,b. The C-glycosidation is b-selective and has been applied further to the preparation of the galactosyl 2,6-imino-d-allonate 19. Solvent effects suggest that the diastereoselectivity originates in the chromium fragment, which shields the re face of the proposed ketene intermediate. The sugar lactams 2 a,b, 8, and 15 a,b were converted to the iminoglycosylidene complexes 3 a ± c, 9, and 16 a,b by an efficient general procedure. [12] Cr(CO) 6 was allowed to react with a suspension of C 8 K in THF at À 78 8C to produce K 2 Cr(CO) 5 . Addition of a solution of the appropriate lactam in THF, followed by the introduction of TMSCl, formed the carbene complexes 3 a,b and 16 a,b in good yield, but the Abstract in German: Die Iminoglycosylidenkomplexe 3 a,b, 9 und 16 a,b können leicht aus den Zuckerlactamen 2 a,b, 8 und 15 a,b durch Reaktion mit K 2 Cr(CO) 5 und nachfolgender Deoxygenierung durch Chlortrimethylsilan dargestellt werden. Die Pentacarbonylchrom-stabilisierte Carbenfunktionalität in den Imino-d-ribo-pyranosyliden-Komplexen 9 und 16 a,b wurde durch Bestrahlung mit UV-Licht für die photoinduzierte Generierung von ketenähnlichen Spezies ausgenutzt, welche durch Methanol unter Bildung der 2,6-Imino-d-allonsäuremethylester 10 und 17 a,b abgefangen wurden. Die C-Glycosidierung verläuft b-selektiv und wurde auf die Darstellung des Galactosyl-2,6-imino-d-allonates 19 übertragen. Lösungsmitteleffekte wiesen darauf hin, daû die Diastereoselektivitäten durch das Chromfragment gesteuert werden, welches die re-Seite des angenommenen Ketenintermediates abschirmt.Scheme 3. Synthesis of the sugar lactams 2 a,b.
“…(1) In the i.r.-absorption spectrum of compound U-7NAc, two strong bands at 1655 and 1545 cm-' were readily attributed to C=O stretching and N-H bending of a secondary amide group respectively. A strong band at 1695 cm-' was assigned to C=O stretching of a y-lactam group on the basis of literature data (Bellamy, 1958;Hanessian, 1969).…”
An unknown amino sugar, U-7, which had been detected in the hydrolysate of the polysaccharide fraction (F-A) of Pseudomonas aeruginosa P14 lipopolysaccharide, was isolated from the hydrolysate of whole cells of this micro-organism and converted into the N-acetyl derivative (U-7NAc). On the basis of i.r.-absorption spectrometry, 13C-n.m.r. and 1H-n.m.r. spectroscopy and mass spectrometry, the structure of compound U-7NAc was identified as 2-acetamido-3-amino-2,3-dideoxyhexofuranurono-6,3-lactam. The configuration of compound U-7NAc was then unequivocally identified as 2-acetamido-3-amino-2,3-dideoxy-D-glucofuranurono-6,3-lactam by comparing the synthetic and natural compounds. Compound U-7 and synthetic 2,3-diamino-2,3-dideoxy-D-glucofuranurono-6,3-lactam showed the same behaviour on chromatography. G.l.c.--mass-spectral analyses of fraction F-A and synthetic 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid after methanolyses and trimethylsilylations showed the presence of the same derivative. It was concluded that the amino sugar U-7 was produced from the 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid residue present in fraction F-A.
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