The N-phenylcarbamate 7, derived from 2-acetamido-2-deoxy-~-gluconhydroximo-l,5-lactone (3) and the analogous N-phenylcarbamate 14, derived from chitobionhydroximo-1,5-lactone (10) have been prepared as potential inhibitors of P-N-acetylglucosaminidases. The unambiguous synthesis of the hydroximo-1,5-lactone 3 involves oxidation of the oxime 1, followed by deprotection with Na/NH,.Introduction and Plan. -We have described the synthesis of the hr-phenylcarbamate derived from gluconhydroximo-1,Slactone [I] and the strong inhibition of emulsin by this compound [2], which also inhibits phosphofructokinase b [3].
The syntheses of the unprotected, (Z)-configurated hexon-and pentonhydroximo-lactones 2a--12a by oxidation of D-gluCOSe, cellobiose, D-galactose, D-mannose, 2-acetamido-2-deoxy-~-glucose, u-ribose, and u-arabinose oxime with Mn02, Hg(OAc),, or 0, in the presence of Cu,Cl,/pyridine are described. An (E/Z)-pair of protected hydroximo-lactones 14 and 15 was obtained by oxidation of the diisopropylidene-u-mannose oxime 13 with MnO,. In CH,CI, solution, the minor (E)-isomer 15 was slowly transformed into the major (Z)-isomer 14. The structure assignments for 2a-12a are based upon IR and NMR data, the Beckmann rearrangement of 1 and 14, and the X-ray structure analysis of 7a and 47. From the selectively deprotected hydroximo-lactones 2c, Sc, and 9c, the urethanes 2d, 2f, Sd, and 9d were prepared. (E/Z)-mixtures of the amino phosphates 27/28, 29/30, and 31/32 were obtained from the bromonitroso ethers 16, 19, and 17 and NdPO(OEt)2. The configuration of the bromonitroso ethers 18 and 19 were assigned on the basis of their CD spectra and of their correlation with the corresponding bromonitro ethers 24 and 25. Factors influencing the configuration of the hydroximo-lactones are briefly discussed.
At pH 4.5 (citrate buffer), o-gluconhydroximo-iactone (2), the N-methylurethane 3 and the Nphenylurethane 4 inhibit competitively the hydrolysis ofp-nitrophenyl B-o-glucopyranoside by emulsin. The IC,, values of 2, 3, and 4 were 1.6 x M, respectively. The K, values of 2 and 4 were 9.8 x lo-' and 2.3 x 10@ M, respectively, while D-glucono-1,S-lactone (1) showed IC,,= 1.1 X M and K, = 3.7 x 10-5 M.
1-C-Nitroglycals. Preparation and Reaction with Some Nitrogen NucleophilesAcetylation of the I-deoxy-1-nitromannopyranoses 2 and 6 was accompagnied by spontanous 8-elimination to give the 1-C-nitroglucals 3 and 7, respectively, while acetylation of the gluco-and galucto-contigurated I-deoxy-1-nitropyranoses 8 and 14 gave the acetates 9 and 15, respectively (Scheme I). The acetylation of the riboand urahino-contigurated I-deoxy-I-nitrofuranoses 19 and 21 also occurred without 8-elimination to give the acetates 20 and 22, respectively (Scheme 2). Mild base treatment of the previously described U-acetylnitro-B-oglucose 4, the 0-acetylnitro-/I-D-pyranoses 9 and 15, and the 0-acetylnitro-8-D-furanoses 17, 20, and 22 gave the I-C-nitroglycals 3,10,16,18 and 23, respectively (Scheme I and 2). The previously obtained I-C-nitroglucal3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m-nitrophenolate to give the free nitroglucal 5. Deacetylation of the benzylidene protected I-C-nitroglucal 10 (MeOH, NaOMe) gave the 4,643-benzylidene-I-C-nitroglucal 11 and traces of the 2-0-methyl-1-C-nitromannoses 12 and 13. The UV, IR, 'H-NMR and I3C-NMR spectra of the I-C-nitroglycals are discussed. In solution, the I-C-nitroglycals 1, 5,7,10,11, and 16 adopt approximately a 4H5-and 3 a flattened 4H5 conformation. The structure of 5 was established by X-ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H-bond. The 8-addition of NH, to the 1-C-nitroglucals 7 and 10 was followed by an O+N acetyl migration to give exclusively anomeric pairs of the N-acetyl-1-nitromannosamine derivatives 24/25 and 26/27, respectively (Scheme 3). The /I-addition of methylamine, octadecylamine, and tryptamine to the 1-C-nitroglucal 11 also stereoelectronically controlled and gave the crystalline N-alkyl-1-nitromannosamines 28,29, and 30, respectively. The stereoelectronically controlled /I-addition of NH, to the 1-C-nitrogalactal 16, followed by acetylation, yielded exclusively the talosamine derivative 31, while the reversible 8-addition of azide ions to 16 gave the anomeric 2-azido-I-nitrogalactoses 32 and 33. The @-addition of azide ions to the I-C-nitroglucal 1 led to the 2-azido-I-nitromannose 34. In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NOz group to give the 3-azidomannoheptulose 35 in high yields (Scheme 4 ) .
, and 4,6-0-benzylidene-~-~-galactose (see 42) were prepared by ozonolysis of the corresponding nitrones which were obtained from the acid-catalyzed reaction of p-nitrobenzaldehyde with the hydroxylamine 4, the unprotected oximes 3 and 5-9 and the 4,643 -benzylidenc oximes 3537, respectively (Schemes 1-3). Thegluco-and manno-nitrones 10 and 12 were isolated, and their ring size and their anomeric and ( E / Z ) configurations were determined by NMR spectroscopy and by their transformation into their corresponding nitro derivatives. The structure of the deoxynitroaldoses were determined by NMR spectroscopy, polarimetry, and, in the case of 14, 16, and 17, by formation of the 4,6-O-benzylidene (14+40) or 4,6-0-isopropylidene (16+43, 17-23) derivatives (Scheme 3). Acetylation of the nitroglucopyranose 14, the 2-acetamido-nitroglucopyranose 17, and the nitrogalactofuranose 19 gave the crystalline peracetylated nitroaldoses 22, 24, and 45, respectively (Scheme 4 , Figs. I and 3); acetylation of the nitromannopyranose 16 gave the nitro-arabino-glycal44 (Scheme 4 ) . The structure of the peracetylated nitroglucopyranose 22, the nitroglucosamine 25, the nitrogalactofuranose 45, and the nitroribofuranose 20 were confirmed by X-ray analysis (Figs. 1 4 ) . In all cases, including the b-u-glucopyranose derivative 22, considerably shortening of the (endocyclic) C( 1)-0 bond was observed. Basecatalyzed anomerization of the 8-D-configurated nitroglucopyranose 14, the nitromannopyranose 16, the benzylidene acetal 40 of nitroglucose, and the 2,3,4,6-tetraacetylated glucosamine derivative 24 gave the corresponding nitro-cc-u-aldoses 15, 26,47, and 25, respectively (Scheme 4).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.