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.     

Transformation of the hydrazones of 6-chloro-3-(l-threo-2,3,4-trihydroxy-1-oxobutyl)-2-quinoxalinone into other heterocyclic compounds

The difference in reactivity of the two amino groups in 4-chloro-o-phenylene-diamine allowed it to react with l-threo-2,3-hexodiulosono-1,4-lactone to give, after further reaction with various hydrazines, 6-chloro-3-(1-substituted-hydrazono-l-threo-2,3,4-trihydroxybutyl)-2-quinoxalinones (5-14), whose structures were deduced from their reactions, as well as from mass spectrometry of the (p-nitrophenyl)-hydrazone. Elimination of one mole of water per mole from these hydrazones gave the 1-aryl-6-chloro-3-(l-threo-glycerol-1-yl)flavazoles; the mass spectrum of one of these flavazoles is discussed. Elimination of two moles of water per mole from the hydrazones (5, 7, and 8) occurred with simultaneous cyclization to give 3-[l-aryl-5- (hydroxymethyl)pyrazol-3-yl]-6-chloro-2-quinoxalinones. whose acetylation gave the corresponding- monoacetyl derivatives (that could also be obtained by the action of boiling acetic anhydride on the starting hydrazones). Periodate oxidation of the hydrazones and the flavazole derivatives afforded the corresponding aldehydes (that could react with hydrazines).     

Syntheses and Biological Evaluation of Alkanediamines as Antioxidant and Hypolipidemic Agents

A new series of compounds belonging to N,N′- [bis (1-aryl-6-hydroxy-hex-2-ene-1-one-3-yl)-1,n-alkanediamines (2–5a–f) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds namely 2c, 2e, 4c, 5b, 5c, 5e and 5f exhibit potent antioxidant activity. These compounds have also been evaluated for hypolipidemic activity.     

Synthesis of base substituted 2-hydroxy-3-(purin-9-yl)-propanoic acids and 4-(purin-9-yl)-3-butenoic acids

Alkylation of 6-chloropurine and 2-amino-6-chloropurine with bromoacetaldehyde diethyl acetal afforded 6-chloro-9-(2,2-diethoxyethyl)purine (3a) and its 2-amino congener (3b). Treatment of compounds 3 with primary and secondary amines gave the N6-substituted adenines (5a-5c) and 2,6-diaminopurines (5d-5f). Hydrolysis of 3 resulted in hypoxanthine (6a) and guanine (6b) derivatives, while their reaction with thiourea led to 6-sulfanylpurine (7a) and 2-amino-6-sulfanylpurine (7b) compounds. Treatment with diluted acid followed by potassium cyanide treatment and acid hydrolysis afforded 6-substituted 3-(purin-9-yl)- and 3-(2-aminopurin-9-yl)-2-hydroxypropanoic acids (8-10). Reaction of compounds 3 with malonic acid in aqueous solution gave exclusively the product of isomerisation, 6-substituted 4-(purin-9-yl)-3-butenoic acids (15).     

Reaction of dehydro-d-erythorbic acid and its aryl analogs with ortho-diamines

Condensation of 3-(d-erythro -2,3,4-trihydroxy-l-oxobutyl)-2-quinoxalinone and its 6-chloro derivative (obtained by the reaction of d-erythro-2,3-hexodiulosono-1,4-lactone with ortho-diamines) with aryl- or aroyl-hydrazines gave 3-[l-(phenylhydrazono)-d-erythro-2,3,4-trihydroxybutyl]-2-quinoxalinone (5) and relatives. Whereas boiling acetic anhydride causes the loss of two molecules of water per molecule of such hydrazones, affording, the 3-[5-(acetoxymethyl)-l-arylpyrazol-3-yl]-2-quinoxalinones, identical with those obtained from the l-threo isomer, alkali causes the loss of only one molecule, affording, the corresponding flavazoles. Periodate oxidation of 5 gave 3-[l-(phenylhydrazono)glyoxal-l-yl]-2-quinoxalinone, which afforded the corresponding mixed bis(hydrazones). A similar sequence of reactions was conducted with the aryl analogs, 4-phenyl-2,3-dioxobutano-1,4-lactone and its p-chlorophenyl derivative, whereby the 3-[2-aryl-l-(arylhydrazono)-2-hydroxyethyl]2-quinoxalinones, were prepared; these were transformed into 3-(α-hydroxybenzyl)-flavazoles that gave monoacetyl derivatives.     

Further farnesyl-homogentisic acid derivatives from Otoba parvifolia

The seeds of Otoba parvifolia contain three novel compounds apparently derived from homogentisic acid, rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid and its acetate as well as rel-(1′R,4′S,5′R)-2-(1′-farnesyl-4′,5′-dihydroxy-2′-oxocyclohexan-1′-yl)-acetic acid δ-lactone. The structure of an additional isolate, previously described as 2-(1′-farnesyl-2′-hydroxy-5′-oxocyclohex-3′-en-1′-yl)-acetic acid γ-lactone was revised to rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid δ-lactone.     

Synthesis of Base Substituted 2-Hydroxy-3-(purin-9-yl)-propanoic Acids and 4-(Purin-9-yl)-3-butenoic Acids

Abstract

Alkylation of 6-chloropurine and 2-amino-6-chloropurine with bromoacetaldehyde diethyl acetal afforded 6-chloro-9-(2,2-diethoxyethyl)purine (3a) and its 2-amino congener (3b). Treatment of compounds 3 with primary and secondary amines gave the N⁶-substituted adenines (5a–5c) and 2,6-diaminopurines (5d–5f). Hydrolysis of 3 resulted in hypoxanthine (6a) and guanine (6b) derivatives, while their reaction with thiourea led to 6-sulfanylpurine (7a) and 2-amino-6-sulfanylpurine (7b) compounds. Treatment with diluted acid followed by potassium cyanide treatment and acid hydrolysis afforded 6-substituted 3-(purin-9-yl)- and 3-(2-aminopurin-9-yl)-2-hydroxypropanoic acids (8–10). Reaction of compounds 3 with malonic acid in aqueous solution gave exclusively the product of isomerisation, 6-substituted 4-(purin-9-yl)-3-butenoic acids (15).     

Synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one from a pyranulose glycoside.

The synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one (9) is described. Treatment of pyranulose glycoside with bromine in carbon tetrachloride afforded brompyranulose glycoside in 90% yield. The reaction of (6S)- and (6R)-4-bromo-6-hydroxy-6-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-6H- pyran-3-one (2) in acidic media was examined with the following results: the reaction of 2 with trifluoroacetic acid (TFA) in dioxane afforded a mixture of 5-hydroxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (3) and its furan derivative 5-hydroxy-2-{5-(benzoyloxy)methyl]furan-2-yl}pyran-4-one (4), but the use of hydrochloric acid formed the bromofurfural, 3-bromo-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2-furancarboxyal dehyde only. Acetylation of a mixture (3 and 4) with acetic anhydride facilitated product separation to give the corresponding acetates 5-acetoxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (5) and 5-acetoxy-2-{5-[(benzoyloxy)methyl]furan-2-yl}pyran-4-one (6). Treatment of 5 with hydrazine afforded 3-hydroxymethyl-6-(beta-D-ribofuranosyl)-1H-pyridazin-4-one in 43% yield. Debenzoylation of 5 with aq ammonia gave 9 in 50% yield.     

On the ring transformation of hydrazine derivatives of l-ascorbic acid into nitrogen heterocyclic derivatives

l-hreo-2,3-hexodiulosono-1,4-lactone 2-(p-methoxyphenylhydrazone) (1) was condensed with arylhydrazines to give mixed bishydrazones, whose acetylation gave the corresponding di-O-acetyl derivatives. The hydrazone 1 undergoes elimination of one molecule of water per molecule during, the acetylation, and gives 4-(2-acetoxy- ethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(p-methoxyphenylhydrazone), which reacts with methylhydrazine, via a ring transformation process, to give 1-methyl-3-(L-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(p-methoxyphenylhydrazone). Alkali rearranged the mixed bishydrazones to 1-aryl-3-(l-threo-glycerol-1-yl)-4,5- pyrazoledione 4-(p-methoxyphenylhydrazones), which gave triacetyl and tribenzoyl derivatives, and, upon periodate oxidation, afforded 1-aryl-3-formyl-4,5- pyrazolediones 4-(p-methoxyphenylhydrazones) that gave the corresponding phenylhydrazones. The n.m.r. and mass spectra of some of these derivatives have been investigated.     

Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazol

The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and D-galacto-pentitol-1-yl)-1H-1,2,4-triazoles (8 and 9) were obtained in a one pot by deamination and dethiolation of 4-amino-3-(D-gluco- and D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazoles (1 and 2), respectively, using sodium nitrite in orthophosphoric acid and subsequent acetylation. Condensation of 1, 2, and 4-amino-3-(D-glycero-D-gulo-hexitol-1-yl)-5-mercapto-1,2,4-triazole (12) with phenacylbromide (11) afforded the corresponding 3-(D-gluco-, D-galactopentitol-1-yl) and 3-(D-glycero-D-gulo-hexitol-1-yl)-6-phenyl-7H-1,2,4-triazolo[3,4-b][1,3,4] thiadiazines (15, 16, and 17). Acetylation of 15-17 gave the penta- and hexa-O-acetyl derivatives 18-20, respectively. The structures were confirmed by using 1H, 13C, and 2D NMR spectra, DQFCOSY, HMQC, and HMBC experiments. The favored conformational structures were deduced from the vicinal coupling constants of the protons.     

Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate

We synthesized a series of novel small molecules, ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate derivatives 3a–3o, by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 2-aryloxymethylepoxide in the presence of potassium carbonate at refluxing in acetonitrile in moderate or excellent yields. We investigated the effects of all the compounds on A549 cell growth. The results showed that 15 compounds could suppress A549 lung cancer cell growth. Among them, compound 3i was the most effective small molecule in inhibiting A549 cell growth. Compound 3f might most effectively induce A549 cell differentiation. Compound 3g remarkably induced cellular vacuolation.     

Synthesis of novel vasodilatory active nicotinate esters with amino acid function

A variety of N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]amino acid esters 6a–h were synthesized through the reaction of 2-bromonicotinates 4 with a number of primary amino acid ester hydrochlorides 5 in refluxing tetrahydrofuran in the presence of triethylamine as dehydrohalogenating agent. Similarly, reaction of 4 with N-glycylglycine ethyl ester hydrochloride 7 ‘as a representative example of dipeptide derivative’ afforded smoothly the corresponding N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]-N′-glycylglycine ethyl ester analogues 8. However, reaction of 4 with 5 in refluxing pyridine yielded the unexpected 2-aminonicotinate esters 9. Vasodilation activity screening for the synthesized nicotinate esters was investigated in vitro on the contractile response of vascular thoracic aorta smooth muscle from Wistar rats, where all the tested compounds exhibit considerable vasodilatory properties. In addition, few prepared compounds especially, 6b, 6h and 9b reveal remarkable vasodilation potency (IC₅₀).     

Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents

Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen–Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI₅₀ values ranging from 0.04 to 11.4 μM, from the in vitro assays.     

Synthesis and Fungicidal Activity of 5-Aryl-1-(aryloxyacetyl)-3-(tert-butyl or phenyl)-4-(1H-1,2,4-triazol-1-yl)-4,5-Dihydropyrazole

A series of novel 5-aryl-1-(aryloxyacetyl)-3-(tert-butyl or phenyl)-4-(1H-1,2,4-triazol-1-yl)-4,5-dihydropyrazole 3a-3n were synthesized by the annulation of 2-aryloxyacetohydrazides with 3-aryl-1-t-butyl(or phenyl)-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones(1)in the presence of a catalytic amount of acetic acid.Compounds 2 were obtained by the Knoevenagel reactions of 1-t-butyl(or phenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone(2)with aromatic aldehydes in the presence of piperidine.Their structures were confirmed by IR,1H-NMR,ESIMS,and elemental analyses.The preliminary bioassay indicated that some compounds displayed moderate to excellent fungicidal activity.For example,compounds 31,3m,and 3n possessed100%inhibition against Cercospora arachidicola Hori at the concentration of 50 mg/L.     

Isolation and identification of the intermediates during pyrazole formation of some carbohydrate hydrazone derivatives

Reaction of the oxidation product of L-ascorbic acid, dehydro-L-ascorbic acid, with o-phenylenediamine, followed by 2,4,6-trichlorophenylhydrazine (3) afforded 3-[1-(2,4,6-trichlorophenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one (4), whose structure was deduced from studying its periodate oxidation, which gave the glyoxal derivative 3-[1-(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1H)one (5) that upon reduction afforded 3-[1-(2,4,6-trichlorophenylhydrazono)-2-hydroxyethy-1-yl]quinoxalin-2(1H)one (6). The reaction of 5 with 3 afforded the bishydrazone 3-[1,2-bis(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1H)one. The reaction of 5 with acetic anhydride in pyridine afforded the 2,3-dihydrofuro[2,3-b]quinoxaline derivative 2-acetoxy-3-[2-acetyl-2-(2,4,6-trichlorophenyl)hydrazono)]-2,3-dihydrofuro[2,3-b]quinoxaline. Acetylation of 4 with acetic anhydride in pyridine afforded the acyclic diacetate intermediate 3-[3,4-di-O-acetyl-2-deoxy-1-(2,4,6-trichlorophenylhydra-zono)but-2-en-1-yl]quinoxalin-2(1H)one (12), which was also obtained from the reaction of 4 with boiling acetic anhydride. Compound 12 rearranged under the reaction conditions to give the pyrazole derivatives 3-[5-(ace-toxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (14) and 2-acetoxy-3-[5-(acetoxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl)]quinoxaline (15), as well as the 2,3-dihydrofuro[2,3-b]quinoxaline derivative 2-(2-acetoxyethen-2-yl)-3-[2-(2,4,6-trichlorophenyl)hydrazono]-2,3-dihydrofuro[2,3-b]quinoxaline. Acetylation of 3-[5-(hydroxymethyl)-l-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (16) with acetic anhydride in pyridine or 12 with boiling acetic anhydride afforded 15 and 16, respectively. Treatment of 4 with diluted sodium hydroxide afforded the pyrazolo[2,3-b]quinoxaline (flavazole) derivative 1-(2,4,6-trichlorophenyl)-3-(L-threo-glycerol-1-yl)pyrazolo[2,3-b]quinoxaline whose acetylation afforded the acetyl derivative 3-(2,3,4-tri-O-acetyl-L-threo-glycerol-1-yl)-1-(2,4,6-trichlorophenyl)pyrazolo[2,3-b]quinoxaline. The assigned structures were based on spectral analysis. The activity of compound 4 against hepatitis B virus has been studied.     

3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors

A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4–10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4-methanesulfonylphenyl)-3-(2-methoxytetrahydrofuran-2-yl)-1-p-tolyl-1H-pyrazole 5 showed potent and selective COX-2 inhibition (IC₅₀ for COX-1: >100 μM and COX-2: 1.2 μM).     

Identification of antibacterial and antiviral activities of novel fused 1,2,4-triazine esters

The in vitro biological activities of novel derivatives of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetates (3a, 3d-j) have been evaluated and are reported. The final heterobicycles (3a-j) were obtained from monocyclic 1-aryl-2-hydrazonoimidazolidines (2a-f) by addition and cyclization reaction with fumaric acid esters. In particular, compounds 3d and 3e were found to exhibit comparable antibacterial potencies in vitro as that of ampicillin. Heterobicycles of the 3e, 3g and 3j type were screened for their antiviral activities against the selected viruses' DNA (human adenovirus type 5-Ad-5) and RNA (human enterovirus-Echo-9). Simultaneously, their cytotoxicities towards HEK-293 and GMK cells were established. In particular, heterobicycle 3j, completely non-toxic for GMK cells, was found to exhibit virucidal properties against Echo-9 virus justifying its further investigation as the potential antiviral agent.     

The synthesis of some branched-chain-sugar nucleoside analogues.

1-(2,3-Epoxy-5-O-trityl-beta-D-lyxofuranosyl)uracil was treated with a number of carbon nucleophiles. Ethynyl lithium gave 3'-deoxy-3'-ethynyl-5'-O-trityl-ara-uridine, which was reduced to the corresponding 3'-ethenyl compound. Sodium cyanide gave 3'-cyano-3'-deoxy-5'-O-trityl-ara-uridine which upon alkaline hydrolysis gave the corresponding 3'-carboxamido compound. 1,3-Dithian-2-yl lithium gave 3'-deoxy-3'-(1,3-dithian-2-yl)-5'-O-trityl-ara-uridine. The trityl group was removed from each of these compounds by mild acidic hydrolysis. Treatment of 2 with 0.1M H2sO4 and mercury (II) acetate afforded 3'-acetyl-3'-deoxy-ara-uridine which upon reduction with NaBH4 gave 3'-deoxy-3'-(1-hydroxyethan-1-yl)-ara-uridine. Acetylation of 6 yielded 5'-O-acetyl-3'-acetyl-2',3'-didehydro-2',3'-dideoxyuridine which upon reduction with NaBH4 produced a mixture of 5'-O-acetyl-2',3'-didehydro-2',3'-dideoxy-3'-(1-hydroxyethan -1-yl)uridine and 1-(R)[5-(S)-acetoxymethyl-4-(1-hydroxyethan-1-yl)-tetrahydrofuran- 2-yl]- uracil. Reduction of 14 with Raney nickel followed by removal of the trityl group gave 3'-deoxy-3'-methyl-ara-uridine.     

Synthesis of a series of ganglioside GM3 analogs containing a deoxy-N-acetylneuraminic acid residue.

Ganglioside GM₃ analogs containing 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-β- - galactopyranosyl)-(1 → 4)-2,6-di-O-benzoyl-β- -glucopyranoside with the methyl 2-thioglycoside derivatives of the respective deoxy-N-acetylneuraminic acids, using dimethyl(methylthio)sulfonium triflate as a promoter, gave the four required 2-(trimethylsilyl)ethyl -sialosyl-(2 → 3b)-β-lactosides. These were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding -sialosyl-(2 → 3b)--lactose trichloroacetimidates 15, 17, 19, and 21. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 15, 17, 19, and 21 in the presence of boron trifluoride etherate afforded the expected β glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target compounds.     

Cooperative aspects of hydrogen bonding in carbohydrates

Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro-l-ascorbic acid or its d-erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-(l-threo-glycerol-1-yl)-1-phenyl- and -1-(p-sulfamylphenyl)-4,5-pyrazole-dione 4-(p-sulfamylphenlhydrazone) and the related 3-(d-erythro-glycerol-1-yl)compounds. Whereas acetylation of l-threo-2,3-hexodiulosono-1,4-lactone 2,3-bis(p-sulfamylphenylhydrazone) (9) and 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone) (15) gave the O-acetyl derivatives, benzoylation of 15 gave the di-N-benzoy ltri-O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-(p-suIfamylphenylazo) -l-xylo-2-hexulosono-1,4-lactone 2-(p-sulfamylphenylhydrazone). The 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)flavazole (35) was prepared by the rearrangement of 3-[(1-p-sulfamylphenyl)hydrazono-l-threo-trihydroxybutyl]-2-quinoxalinont (33). Periodate oxidation of 15,33, and 35 gave 3-formyl-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone), 3-1-[(p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-(p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.