The preparation of some bromodeoxy- and dibromodideoxy-pentonolactones

Brief reaction of d-lyxono-1,4-lactone (1) with hydrogen bromide in acetic acid (HBA) yields 2-bromo-2-deoxy-d-xylono-1,4-lactone (2), and a similar treatment of d-ribono-1,4-lactone (8) gives 2-bromo-2-deoxy-d-arabinono-1,4-lactone (12). On longer reaction with HBA, 1 is converted into 2,5-dibromo-2,5-dideoxy-d-xylono-1,4-lactone, whereas 8 forms a mixture of 2,5-dibromolactones. Reduction of 2 and 12 gives 2-bromo-2-deoxy-d-xylose and -d-arabinose, respectively. On hydrogenolysis, 2 and 12 are converted into 2-deoxy-d-threo- and 2-deoxy-d-erythro-pentono-1,4-lactone, respectively. The 2,5-dibromolactones can be selectively hydrogenolysed to 5-bromo-2,5-dideoxy-d-pentono-1,4-lactones.     

Preparation of some bromodeoxyaldonic acids

Reaction of L-ascorbic acid with hydrogen bromide in acetic acid gave 6-bromo-6-deoxy-L-ascorbic acid, which was converted into 5,6-dideoxy-D-glycero-hex-2,3-enono-1,4-lactone. Hexonic acids or their lactones also gave bromo compounds on treatment with HBrAcOH. From D-galactono-1,4-lactone a 6-bromo derivative was obtained. Calcium D-gluconate yielded 2,6-dibromo-2,6-dideoxy-D-mannono-1,4-lactone, whereas D-mannono-1,4-lactone gave 2,6-dibromo-2,6-dideoxy-D-glucono-1,4-lactone.     

Studies on dehydro-l-ascorbic acid 3-oxime 2-phenylhydrazone: Conversion into substituted triazoles

l-threo-2,3-Hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone) (1) gave 2-(p-bromophenyl)-4-(l-threo-1,2,3-trihydroxypropyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (2), and this gave a diacetyl and a dibenzoyl derivative. On treatment of 2 with liquid ammonia, methylamine, or dimethylamine, the corresponding triazole-5-carboxamides (5–7) were obtained. Periodate oxidation of 5 gave 2-(p-bromophenyl)-4-formyl-1,2,3-triazole-5-carboxamide (10), and, on reduction, 10 gave 2-(p-bromophenyl)-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamide, characterized as its monoacetate. Condensation of 10 with phenylhydrazine gave the triazole hydrazone. Acetonation of 2 gave the isopropylidene derivative. Reaction of 2 with HBr-HOAc gave 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-(p-bromophenyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone. Similar treatment of 1 with HBr-HOAc gave 5-O-acetyl-5-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone). This was converted into 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with boiling acetic anhydride. On reaction of 1 with benzoyl chloride in pyridine, dehydrative cyclization occurred, with the formation of 4-(l-threo-2,3-dibenzoyloxy-1-hydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone, which was converted into the amide on treatment with ammonia.     

Improved preparation and synthetic uses of 3-deoxy-d-arabino-hexonolactone: an efficient synthesis of Leptosphaerin

Acetylation of d-glucono-1,5-lactone and subsequent treatment with triethylamine gave 2,4,6-tri-O-acetyl-d-erythro-hex-2-enono-1,5-lactone. Hydrogenation of the latter in the presence of palladium on carbon yielded 2,4,6-tri-O-acetyl-3-deoxy-d-arabino-hexono-1,5-lactone (5) in almost quantitative yield calculated from gluconolactone. Catalytic hydrogenation of 5 with platinum on carbon in the presence of triethylamine gave 2,4,6-tri-O-acetyl-3-deoxy-d-arabino-hexopyranose in quantitative yield. Deacetylation of 5 gave 3-deoxy-d-arabino-hexono-1,4-lactone, which was converted into 3-deoxy-5,6-O-isopropylidene-2-O-methanesulfonyl-d-arabino-hexono-1,4-lactone (10). The latter was converted into 2-acetamido-2,3-dideoxy-d-erythro-hex-2-enono-1,4-lactone (Leptosphaerin). When 10 was boiled in water in the presence of acid, it gave a high yield of 2,5-anhydro-3-deoxy-d-ribo-hexonic acid.     

Studies on dehydro-l-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

l-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro-l-ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-(l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-(l-threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-l-threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.     

Studies on dehydro-d-arabino-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

d-erythro-2,3-Hexodiulosono-1,4-lactone 2-arylhydrazones (2) were prepared by condensation of dehydro-d-arabino-ascorbic acid with the desired arylhydrazine. Reaction of 2 with hydroxylamine gave the 2-arylhydrazone 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (5), whereas the unacetylated triazole derivatives were obtained upon reaction of 3 with bromine in water. On treatment of 5 with hydrazine hydrate, 2-aryl-4-(d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides (6) were obtained. Acetylation of 6 gave the hexaacetyl derivatives. Similarly, treatment of 5 with liquid ammonia gave the triazolecarboxamides (12). Vigorous acetylation of 12 with boiling acetic anhydride gave tetraacetates, whereas acetylation with acetic anhydride-pyridine gave triacetates. Periodate oxidation of 6 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxylic acid 5-hydrazides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides, characterized as acetates. Similarly, periodate oxidation of 12 gave the triazolealdehyde (15), and reduction of 15 gave the hydroxymethyl derivatives (16). Acetylation of 16 gave the mono- and di-acetates, and, on reaction with o-phenylenediamine, 15 afforded the triazoleimidazole. Controlled reaction of 3 with sodium hydroxide, followed by neutralization, gave 3-(d-erythro-glycerol-1-yl)-4,5-isoxazolinedione 4-arylhydrazones. Reaction of 3 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-d-erythro-2,3-hexodiulosono-1,4-lactone 2-arylhydrazone 3-oximes (21). Compounds 21 were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-d-erythro-glycerol-1-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with acetic anhydride.     

β-elimination in aldonolactones. Synthesis of 2-deoxy-D-lyxo-hexose and 2-deoxy-D-arabino-hexose

Benzoylation of D-glycero-L-manno-heptono-1,4-lactone (1) with benzoyl chloride and pyridine for 2 h afforded crystalline penta-O-benzoyl-D-glycero-L-manno-heptono-1,4-lactone (2), but a large excess of reagent during 8 h also led to 2,5,6,7-tetra-O- benzoyl-3-deoxy-D-lyxo-hept-2-enono-1,4-lactone (3). Catalytic hydrogenation of 3 was stereoselective and gave 2,5,6,7-tetra-O-benzoyl-3-deoxy-D-galacto-heptono-1,4-lactone (4). Debenzoylation of 4 followed by oxidative decarboxylation with ceric sulfate in aqueous sulfuric acid gave 2-deoxy-D-lyxo-hexose (5). Application of the same reaction to 3-deoxy-D-gluco-heptono-1,4-lactone afforded 2-deoxy-D-arabino-hexose (6).     

Studies on dehydro- -ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro- -ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl- -threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-( -threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-( -threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy- -threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy- -threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.     

The inhibitory activity of 2-acetamido-2-deoxy-D-gluconolactones and their isopropylidene derivatives on 2-acetamido-2-deoxy-beta-D-glucosidase

2-Acetamido-2-deoxy-D-glucono-1,4-lactone (1) and 2-acetamido-2-deoxy-D-gluconic acid (3) have been examined for inhibitory activity against 2-acetamido-2-deoxy-β-D-glucosidase from bull epididymis. Crystalline 1 and 3 were compared with the known, crystalline 2-acetamido-2-deoxy-D-glucono-1,5-lactone (2), and a correlation of the activities of these compounds with various factors is presented. The inhibition constant of the 1,5-lactone 2 is lower (0.45μM) than that (4.43μM) of the 1,4-lactone 1. The effect of time is the opposite; whereas the activity of solutions of 2 decreases with time, solutions of 1 show an increase in inhibitory power, but both reach an equilibrium after 5 h. The free acid 3 exhibits no inhibitory activity. 2-Acetamido-2-deoxy-5,6-O-isopropylidene-D-glucono- 1,4-lactone (4) and 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-glucono-1,5-lactone (5), which are appropriately protected to prevent conversion into the other lactone isomer, were also tested; 4 has 1/1000th the activity of 5.     

Synthesis of new N-substituted 3,4,5-trihydroxypiperidin-2-ones from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 8a in quantitative yield. Using this reaction procedure, N-butyl, N-hexyl, N-dodecyl, N-benzyl, N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-d-ribonamides 8b-h were obtained in quantitative yield. Bromination of the amides 8a-e with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-ethyl, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonamides 9a-e in 40-54% yields. To obtain 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-9f-h, the bromination is necessary before the amidation reaction. Treatment of the bromoamides 9a-h with NaH in DMF followed by methanolysis affords N-alkyl-d-ribono-1,5-lactams 12a-h in quantitative yield.     

Synthesis and structural characterizations of para-bis(dialkyl/diarylphosphino)phenylenes built around tetrahalogenated benzene cores

Double deprotonation of 1,2-dibromo-4,5-difluorobenzene and 1-bromo-2-chloro-4,5-difluorobenzene by lithium diisopropylamide (LDA) in ethereal solutions is facile at very low temperatures (T < −90 °C). The organo-dilithium intermediates thus generated react readily with chlorophosphines ClPR₂ (R = Ph and/or ⁱPr), producing 1,2-dibromo-3,6-bis(diphenylphosphino)-4,5-difluorobenzene (1a), 1,2-dibromo-3,6-bis(diisopropylphosphino)-4,5-difluorobenzene (1b) and 1-bromo-2-chloro-3,6-bis(diphenylphosphino)-4,5-difluorobenzene (1c). Corresponding P-oxides 2a-c are obtained by oxidation of 1a-c with H₂O₂. Analogous reactions of 1,2-dibromo-4,5-difluorobenzene and 1-bromo-2-chloro-4,5-difluorobenzene with only 1 equiv. of LDA do not result in selective monodeprotonations, as 1a and 1c are formed preferentially after ClPPh₂ quench. All of the isolated new compounds were fully characterized by multinuclear NMR spectroscopy, elemental analysis and/or mass-spectrometry. In addition, 1a, 1c, 2a, and 2b were characterized by single crystal X-ray diffraction methods.     

Studies in the sphingolipids series,XXXII : Synthesis and resolution into optical antipodes of C20-phytosphingosine

C₂₀-Phytosphingosine, D(+)-ribo-2-amino-1, 3, 4-trihydroxyeicosane (8a), is synthesized through the following intermediates: 2-Methoxyoctadecanoic acid chloride (1)→Ethyl 2-methoxyoctadecanoylacetoacetate (2)→Ethyl (2-p-nitrophenylhydrazono)-2,3-dioxo-4-methoxyeicosanoate (3)→Ethyl 2-acetamido-3-oxo-4-methoxyeicosanoate (4)→Ethyl 2-acetamido-3-hydroxy-4-methoxyeicosanoate (5)→2-Acetamido-3-hydroxy-4-methoxyeicosanoic acid (6), 2-Amino-3-hydroxyeicosanoic acid 1,4-lactone hydrobromide (7a, b)→DL-ribo (8a) and DL-xylo(?)-2-amino-1,3,4-trihydroxyeicosane (8b). The resolution of the racemic base (8a) has been effected through its salts with D-tartaric acid.     

Synthesis of some C-glycosyl- and polyhydroxyalkyl-pyridazines

Photo-oxygenation of 3-hydroxymethyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran, 5-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-3-(1-hydroxyethyl)-2-methylfuran (8a), and 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoic acid (8b) yielded the corresponding endo-peroxides, which were transformed into 4-hydroxymethyl-6-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-3-methylpyridazine, 6-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-4-(1-hydroxyethyl)-3-methylpyridazine, and 6-(d-arabino-tetritol-1-yl)-3-methylpyridazine by treatment with hydrazine. The γ-di-ketones (Z)-1-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-3-(1-hydroxyethyl)pent-2-ene-1,4-dione and d-arabino-6,7,8,9-tetraacetoxy-4-methoxynonane-2,5-dione can be obtained by reduction of the endo-peroxides 9a and 9b (derived from 8a and 8b, respectively) with dimethyl sulphide. The C → O rearrangement reported for C-glycosyl endo-peroxides was also observed for 9a.     

Some studies on dehydro-d-ascorbic acid 2-(phenylhydrazone)

Reaction of hydroxylamine with d-erythro-2,3-hexodiulosono-1, 4-lactone 2-(phenylhydrazone) (2) gave the 3-oxime 2-(phenylhydrazone) (3). On boiling with acetic anhydride, 3 gave 4-(d-erythro-2,3-diacetoxy-l-hydroxypropyl)-2-phenyl-1,2, 3-triazoIe-5-carboxylic acid 5,1′-lactone. Compound 3 was also converted into the related, unacetylated 2-(p-bromophenyl)triazole with bromine. Treatment of 2 with boiling acetic anhydride gave an optically inactive, olefinic compound, assigned the structure 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(phenylhydrazone). The 2-(phenylhydrazone) 2 gave the corresponding 2,3-bis(phenylhydrazone) on condensation with phenylhydrazine.     

Synthèse des 2-amino-2-désoxy-d-arabinono- et -d-xylono-lactones par condensation d'acides aminés avec le d-glycéraldéhyde. Analyse structurale par rayons X de deux dérivés

Synthesis of 2-amino-2-deoxy-d-pentonolactones was performed by diastereoselective hydroxyalkylation of 2,3-O-isopropylidene-d-glyceraldehyde with ethyl isocyanoacetate, to give two oxazolines in a ratio of 7:3. Hydrolysis gave first the corresponding amides, and then the 2-amino-2-deoxypentonolactones. The structure of the 2-amino-2-deoxy-d-arabinono-1,4-lactone was established by X-ray diffraction, indicating exclusive formation of trans-oxazolines and of an “erythro” configuration at C-3C-4 of the major compound.     

Synthesis and evaluation of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines as Bcl-2 inhibitory anticancer agents

A series of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines 8a–j has been designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents based on our previous lead compound 8a. Synthesis of the target compounds was readily accomplished through a cyclisation reaction between indole-3-carboxylic acid hydrazide (5) and substituted isothiocyanates 6a–j, followed by oxidative cyclodesulfurization of the corresponding thiosemicarbazide 7a–j using 1,3-dibromo-5,5-dimethylhydantoin. Active compounds of the series 8a–j were found to have sub-micromolar IC₅₀ values selectively in Bcl-2 expressing human cancer cell lines; notably the 2-nitrophenyl analogue 8a was found to exhibit potent activity, and compounds 8a and 8e possessed comparable Bcl-2 binding affinity (ELISA assay) to the established natural product-based Bcl-2 inhibitor, gossypol. Molecular modeling studies helped to further rationalise anti-apoptotic Bcl-2 binding, and identified compounds 8a and 8e as candidates for further development as Bcl-2 inhibitory anticancer agents.     

An improved synthesis of 5-thio-D-ribose from D-ribono-1,4-lactone

5-Thio-D-ribopyranose was synthesized from D-ribono-1,4-lactone (1) by two approaches: (i) 5-bromo-5-deoxy-D-ribono-1,4-lactone (2) was successively transformed into 5-bromo-5-deoxy, 5-S-acetyl-5-thio or 5-thiocyanato-D-ribofuranose derivatives; appropriate treatment then lead to 5-thio-D-ribopyranose (7) in 46-48% overall yield and; (ii) 2 was transformed into the 5-S-acetyl-5-thio-D-ribono-1,4-lactone derivative (11). Reduction and deprotection of 11 afforded 5-thio-D-ribopyranose (7) in 57% overall yield.     

The 13C-n.m.r. spectra of peracetylated cello-oligosaccharides

The reaction of 1,4-anhydro-2-deoxy-5,6-O-isopropylidene-d-arabino-hex-1-enitol (1) with m-chloroperbenzoic acid in ethanol gives 2,3-unsaturated ethyl glycosides together with saturated ethyl glycosides formed by trans-ring opening of 1,2-epoxide intermediates. Similar results are obtained on peroxidation of 1,4-anhydro-2-deoxy-3-O-(2,3:5,6-di-O-isopropylidene-α-d-mannofuranosyl)-5,6-O-isopropylidene-d-arabino-hex-1-enitol (2). Products resulting from osmylation of 1 and 2 and cleavage of the osmate esters are also described. 2-Deoxy derivatives are prepared from 1 and 2 by methoxymercuration-demercuration and also by reduction of 2-bromo-2-deoxy derivatives obtained by ethoxybromination.     

Biosynthesis of chondroitin sulfate. Purification of UDP-D-xylose:core protein beta-D-xylosyltransferase by affinity chromatography

Silver carbonate on Celite (the Fetizon reagent) was shown to be selective as an oxidizing agent, and convenient for the preparation of various aldonolactones. Whereas substituted aldoses having the 1-hydroxyl group free were readily converted into the corresponding lactones, partially protected 2-acetamido-2-deoxypyranoses having more than one free hydroxyl group were selectively oxidized at C-1. The oxidation was carrried out in boiling benzene or 1,4-dioxane. A series of partially protected 2-acetamido-2-deoxy-1,5-aldonolactones [2-acetamido-4,6-O-benzylidene-2-deoxy-D-mannono-1,5-lactone (13),2-acetamido-4,6-O-benzylidene-2-deoxy-D-glucono-1,5-lactone (15), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-glucono-1,5-lactone (18), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-mannono-1,5-lactone (20), 2-acetamido-2-deoxy-3,4-di-O-methyl-D-mannono-1,5-lactone (24), and 2-acetamido-2-deoxy-3,4-di-O-methyl-D-glucono-1,5-lactone (25)] was thus prepared; for these, the oxidation was accompanied by two side-reactions: (a) an elimination (dehydration) that gave the unsaturated lactones [2-acetamido-4,6-O-benzylidene-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (12), 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-D-erythro-hex-2-enono-1,5-lactone (17), and 2-acetamido-2,3-dideoxy-4-O-methyl-D-erythro-hex-2-enono-1,5-lactone (23)], and (b) partial gluco-to-manno epimerization occurring during the oxidation of 2-acetamido-4,6-O-benzylidene-2-deoxy-D-glucopyranose (14), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-glucopyranose (16), and 2-acetamido-2-deoxy-3,4-di-O-methyl-D-glucopyranose (22).The free unsaturated lactone, 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (26), was obtained on hydrolysis of the isopropylidene group in lactone 17.     

Facile synthesis and rearrangement of L-threo-2,3-hexodiulosono-1,4-lactone 2-(2-arylhydrazones)

Controlled reaction of L-threo-2,3-hexodiulosono-1,4-lactone with substituted phenylhydrazines gave the 2-(monoarylhydrazones) (2), which underwent dehydrative acetylation to 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxohutyro-1,4-lactone 2-(2-arylhydrazones) (3). The latter reacted with methylhydrazine to give 1-methyl-3-(1-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(2-arylhydrazones) (4). Reaction of the monoarythydrazones (2) with phenylhydrazine gave the mixed bishydrazones (5), which were rearranged by alkali and acidification to the pyrazolediones (6). Compounds 6 gave triacetyl (7) and tribenzoyl derivatives (8), and, on periodite oxidation, the aldehydes (9), which afforded the monohydrazones (10). The i.r.. n.m.r.. and mass-spectral data of some of the compounds were investigated.