O-benzoyl Derivative Research Articles

Stereoselectivities in the reaction of methyl 4,6- O-benzylidene-α- and -β- d-hexopyranosid-2-uloses with diazomethane

The stereoselectivities in the reaction with diazomethane of methyl 4,6- O benzylidene-3- O-methyl-α- d- arabino-hexopyranosid-2-ulose ( 2), its 3-epimer ( 3), its β anomer ( 5), and the corresponding 3- O-benzoyl derivative ( 4) have been examined in comparison with those in the Grignard reaction and in reduction with sodium borohydride. The opposite stereoselectivity of the diazomethane reaction, with equatorial attack on α anomers ( 2 and 3) and axial attack on β anomers ( 4 and 5), to that of the other reactions, is explained by an attractive, electrostatic interaction in the transition state between the diazomethyl cation and either the axial O-1 of the methoxyl group or lone-pair electrons of O-5.

Acylation of pyran-2,4,6-trione (acetonedicarboxylic anhydride)

The reaction of acetone-1,3-dicarboxylic acid with acetic anhydride at 40–50 °C gives 4-acetoxypyran-2,6(3H)-dione. This O-acetyl derivative can be converted into the C-acetyl derivative, 3-acetylpyran-2,4,6-trione. Pyran-2,4,6-trione reacts with benzoyl chloride to yield the O-benzoyl derivative, 4-benzoyloxypran-2,6(3H)-dione, whereas the reaction with ethoxycarbonylacetyl chloride gives the bis-C-acyl derivative, 3,5-bis(ethoxycarbonylacetyl)pyran-2,4,6-trione.

Synthesis of daunosamine

The rearrangement of methyl 3-azido-2- S-benzyl-3-deoxy-2-thio-α- D-altropyranoside ( 3) in methanol to give methyl 3-azido-2- S-benzyl-3-deoxy-2-thio-αβ- D-altrofuranoside ( 4a) was catalysed by Amberlite CG-120(H +) resin. Partial benzoylation of 4a gave the 6- O-benzoyl derivative ( 4b), the 5- O-toluene- p-sulphonyl derivative ( 4c) of which was converted into methyl 5,6-anhydro-3-azido-2- S-benzyl-3-deoxy-2-thio-αβ- L-galactofuranoside ( 7) with methanolic sodium methoxide. Reduction of 7 with lithium aluminium hydride gave the 3,6-dideoxy sugar ( 8a) which, with Raney nickel, gave methyl 3-amino-2,3,6-trideoxy-αβ- L- lyxo-hexofuranoside ( 9). Acid hydrolysis of 9 gave 3-amino-2,3,6-trideoxy- L- lyxo-hexose (daunosamine) which is a component of the antibiotic daunomycin.

Preparative syntheses of 2,6-dideoxy-α- L- lyxo-hexose (2-deoxy-α- L-fucose) and its D- ribo epimer (digitoxose)

Methyl 4,6- O-benzylidene-2-deoxy-α- D- ribo-hexopyranoside ( 1) is converted into methyl 3,4-di- O-benzoyl-6-bromo-2,6-dideoxy-α- D- ribo-hexopyranoside ( 3) via the 3- O-benzoyl derivative ( 2) of 1 by subsequent treatment with N-bromosuccinimide. Compound 3 is the key intermediate in high-yielding, preparative syntheses of the title dideoxy sugars, which are constituents of many antibiotics. Dehydrohalogenation of 3 affords the 5,6-unsaturated glycoside 7. which undergoes stereospecific reduction by hydrogen with net inversion at C-5 to give methyl 3,4-di- O-benzoyl-2,6-dideoxy-β- L- lyxo-hexopyranoside ( 8), whereas reductive dehalogenation of 3 provides the corresponding D- ribo derivative 4. The unprotected glycosides 9 ( L- lyxo) and 5 ( D- ribo) are readily obtained by catalytic transesterification, and mild, acid hydrolysis gives the crystalline title sugars 10 ( L- lyxo) and 6 ( D- ribo) in 45 and 57% overall yield from 1 without the necessity of chromatographic purification at any of the steps.

Synthesis of 6-azido- and 6-amino-2,3,6-trideoxy- d- erythro-hexose

The synthesis of 6-azido- and 6-amino-2,3,6-trideoxy- d- erythro-hexose ( 19 and 22) and several of their derivatives is described. Hydrogenation and hydrogenolysis of methyl 4,6- O-benzylidene-2,3-dideoxy-α- d- erythro-hex-2-enopyranoside ( 1) gave methyl 2,3-dideoxy-α- d- erythro-hexopyranoside ( 3), which was transformed into methyl 6-azido-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 9) via the 6-tosylate or the 6- O-tris(dimethylamino)phosphonium bromide derivative. The 4-acetate ( 8) or 9 was also prepared from methyl 4- O-acetyl-2,3-dideoxy-6- O-toluene- p-sulphonyl-α- d- erythro-hexopyranoside ( 7). Hydrogenation or 8 in methanol-acetic anhydride gave the diacetate 12. Reduction of 8 in methanol gave a mixture (1:2) of unstable 4- O-acetyl-6-amino-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 10) and methyl 6-acetamido-2,3,6-trideoxy-α- d- erythro-hexopyranoside. Reduction of 9 afforded methyl 6-amino-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 13). Transformation of 1, via the 6-bromo-4- O-benzoyl derivative 15, into methyl 6-azido-4- O-benzoyl-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 16), followed by O-debenzoylation, afforded 9. Hydrogenation of 16 in the presence of acetic anhydride gave methyl 6-acetamido-4- O-benzoyl-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 17), which yielded 11 on O-debenzoylation. Acid hydrolyses of 3 and 9 liberated the corresponding free sugars 18 and 19. Hydrolysis of 11 gave 6-acetamido-2,3,6-trideoxy- d- erythro-hexopyranose ( 20) and minor amounts of the 1,6-anhydro derivative 21. Acetolysis of 11 afforded 6-acetamido-4- O-acetyl-1,6-anhydro-2,3,6-trideoxy-β- d- erythro-hexopyranose ( 22), the O-deacetylation of which yielded a mixture of the bicyclic compound 21 (major product) and 20.

ChemInform Abstract: STUDIES ON PYRAZOLO(3,4‐D)PYRIMIDINE DERIVATIVES. IV. ON 1‐METHYL‐ AND 1‐PHENYL‐1H‐PYRAZOLO(3,4‐D)PYRIMIDINE 5‐OXIDE

AbstractVerschiedene Reaktionen der durch Kondensation der Pyrazole (I) mit Orthoameisensäureester in 38 ‐ 39%iger Ausbeute erhältlichen Pyrazolopyrimidin‐S‐oxide (II) wurden untersucht.

C-glycosyl compounds. Stereospecific synthesis of 2,5-anhydro- d-allose derivatives via diazotization

A stereospecific synthesis of substituted derivatives of 2,5-anhydro- d-allose via conformational control and diazotization is described. Diazotization of the conformationally mobile methyl 2-amino-2-deoxy-α- d-altropyranoside ( 7) and its 3,4,6-tri- O-benzoyl derivative ( 8) led to a selectively disfavored, ring-contraction reaction, but, for the conformationally rigid 2-amino-1,6-anhydro-2-deoxy-3- O-p-tolylsulfonyl-β- d-altropyranose ( 19), the rearrangement was unequivocally chanenlled stereospecifically, and almost quantitatively, to a 2,5-anhydro- d-alloseptanose derivative ( 21). Conformational assignments and rearrangement mechanisms are discussed. O-Detosylation was achieved by photolysis. The 1,3-dioxolane derivative used for the protection of the anomeric center was found very resistant toward acid hydrolysis, and disadvantageous in the regeneration of the free aldehyde group.

Preferential sulfonylation of methyl 2,6-di- O-mesyl-α- D-glucopyranoside

When equimolar ratios of mesyl chloride and methyl 2,6-di- O-mesyl-α- D-glucopyranoside were allowed to react in pyridine and the product resolved by preparative t.l.c., the 2,6-di-, 2,3,6-tri-, 2,4,6-tri-, and 2,3,4,6-tetra-mesyl esters were obtained in (0.5–0.6):1:(4–5):(1-2-1.4) molar ratio. Benzoylation of either the isolated 2,4,6-tri- O-mesyl ester or, more conveniently, the mixture from monomesylation gave the crystalline methyl 3- O-benzoyl-2,4,6-tri O-mesyl-α- D-glucopyranoside ( 8). As both of these trimesyl esters ( 7 and 8) are unreported, isolation of the benzoate established the 2,4,6-ester arrangement, and the 2,3,6-triester was prepared by standard methods. Treating methyl α- D-glucopyranoside with 3 molar equivalents of mesyl chloride and, subsequently, with 1 molar equivalent of benzoyl chloride, proved a convenient method for preparing the 3- O-benzoyl derivative in moderate yield. Monotosylation of methyl 2,6-di- O mesyl-α- D-glucopyranoside was not so definitive as mesylation, but a molar ratio of 1:2.8 for the 3- O-tosyl:4- O-tosyl product was derived from n.m.r. data. This work, when combined with literature reports, establishes that, in methyl α- D-glucopyranoside, the reactivity toward sulfonylation is 6-OH>2-OH>4-OH>3-OH.

Studies on pyrazolo[3,4-d]pyrimidine derivatives. IV. On 1-methyl- and 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine 5-oxide.

Various reactions usually carried out on heterocyclic N-oxides were examined on 1-methyl-(IIm-0) and 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine 5-oxide (IIp-0) prepared from the condensation-cyclization of 1-methyl-(IIIm-1) or 1-phenyl-5-amino-4-hydroxyiminomethyl-1H-pyrazole (IIIp-1) and ethyl orthoformate. The reaction of IIp-0 with alkaline solution gave the ring fission product between the 5- and 6-position such as 5-formamido- (IIIp-5) and 5-amino-4-hydroxyiminomethyl-1-phenyl-1H-pyrazole (IIIp-1). Application of the Reissert reaction to II-0 resulted in the formation of the ring fission products such as O-benzoyl derivative of IIIp-1 (IIIp-6) and 5-amino-1-methyl-1H-pyrazole-4-carbonitrile (IIIm-3). Acetic anhydride and IIm-0 gave 1-methyl-1H-pyrazolo [3, 4-d] pyrimidin-4-ol-(Im-4). But the reaction with IIp-0 gave both 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-4-ol (Ip-4) and 5-acetamido-1-phenyl-1H-pyrazole-4-carbonitrile (IIIp-8). Ip-4 was also obtained from the reaction of IIp-0 with tosyl chloride. The thermal decomposition of II-0 afforded 4, 4'-bis [1-methyl-1H-pyrazolo [3, 4-d] pyrimidine] (IXm) and 4, 4'-bis [1-phenyl-1H-pyrazolo [3, 4-d] pyrinidime] (IXp) together with 1-methyl-(Im-0) and 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine (Ip-0). The Grignard reaction of II-0 gave 1-Methyl-(IIm-7-9) and 1-phenyl-4-alkyl-1H-pyrazolo-[3, 4-d] pyrimidine 5-oxide (IIp-5-9). Im-0 and II-0 were transformed into 1-methyl-(XIXm) and 1-phenyl-1H-pyrazolo [3, 4-b] pyridines (XIXp) by the reaction with some active methylene compounds or ketone such as malononitrile (A-1), ethyl cyanoacetate (A-2), ethyl acetoacetate (A-3), acetylacetone (A-4) and cyclohexanone (A-5). Thus, in the presence of ethoxide ion Im-0 reacted with A-1 to give 6-amino-1-methyl-1H-pyrazolo [3, 4-d] pyridine-5-carbonitrile (XIXm-1). The direct reaction of IIm-0 with A-1 and A-2 gave 4, 5-dihydro-5-hydroxy-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-malononitrile (XXm) and ethyl α-cyano-4, 5-dihydro-5-hydroxy-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-acetate (XXm-2). But the direct reaction with A-3, 4 and 5 afforded the corresponding XIXm (XIXm-3, 4, and 5), respectively. The reaction of IIp-0 with A-1, 3, and 4 formed the corresponding XIXp (XIXp-1, 3, and 4) together with IXp (in the case of A-3 and 4), Ip-0 (in the case of A-4) and the ring fission product such as ethyl 2-(4-cyano-1-phenyl-1H-pyrazol-5-ylaminomethylene)-3-oxobutyrate (XXIp-3) and ethyl 2-(4-hydroxy-iminomethyl-1-phenyl-1H-pyrazol-5-ylaminomethylene)-3-oxobutyrate (XXIp-3') (in the case of (A-3).

Synthesis and reactions of potassium cyanoacetohydroxamate

The reaction of ethyl cyanoacetate with hydroxylamine gave potassium cyanoacetohydroxamate (I), which cyclised under basic conditions to yield the isoxazolone (IIIa). Reactions of (I) with hydroxylamine and acetylacetone gave α-(hydroxyamidino)acetohydroxamic acid (II) and the cyanopyridone (IV), respectively. The reaction with benzoyl chloride yielded three products [the O-benzoyl derivative (V), the isoxazolone (IIIb), and NO-dibenzoylhydroxylamine] in amounts depending on the reaction conditions.

Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

For the synthesis of y 1-(3′-deoxy-β-D- glycero-pentofuran-2′-ulosyl)uracil ( 16), the precursor, 5′-O-benzoyl derivative ( 2), 2 was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil ( 4) 2 was benzoylated to N 3-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil ( 8) and its 3′,5′-O-isopropylidene analog ( 10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil ( 11) was first benzoylated to give 2′,5′-di-O-benzoate ( 12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product ( 12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil ( 15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.

Synthesis and properties of the stereoisomeric diethyl 2-aminocyclohexane-1,4-dicarboxylates

Nucleophilic addition of ammonia to ethyl 4-cyanocyclohex-3-enecarboxylate (III), followed by hydrolysis and esterification yielded the four stereoisomeric diethyl 2-aminocyclohexane-1,4-dicarboxylates (I). The conformations of these isomers were established by n.m.r. spectroscopy and by stereospecific deaminations to give cyclohexenes or diethyl 2-hydroxycyclohexane-1,4-dicarboxylates (II). N- and O-Benzoyl derivatives of the cyclohexanecarboxylates (I) and (II) respectively are discussed in relation to deshielding effects on α-protons. Diethyl c-2-aminocyclohexane-r-1,c-4-dicarboxylate (Id) undergoes intramolecular cyclisation to give ethyl 7-oxo-6-azabicyclo[3.2.1]octane-4-carboxylate (X).

Synthesis of the 3- and 4-methyl, 3,4-dimethyl, and 3,4,6-trimethyl ethers of methyl 2-acetamido-2-deoxy-α- D-mannopyranoside

The methyl ethers of 2-amino-2-deoxy- D-mannose are reference compounds in studies, by the methylation procedure, of the chemical structure of polysaccharides containing 2-amino-2-deoxy- D-mannose and 2-amino-2-deoxy- D-mannuronic acid residues. Methylation of methyl 2-acetamido-2-deoxy-α- D-mannopyranoside ( 1) gave the 3,4,6-trimethyl ether. Methylation of the 6-trityl ether of 1, followed by detritylation, gave the 3,4-dimethyl ether of 1. Methylation of the 4,6- O-benzylidene derivative ( 6) of 1, followed by removal of the benzylidene group, gave the 3-methyl ether of 1. Benzoylation of 6, followed by removal of the benzylidene group and monobenzoylation, gave the 3,6-dibenzoate of 1, which was methylated, and the product saponified, to give the 4-methyl ether of 1; the latter compound was also obtained by a similar route via the 3- O-acetyl-6- O-benzoyl derivative.

Sucrochemistry : Part VI. Further reactions of 6,6′- DI- O-tosylsucrose and a comparison of the reactivity at the 6 and 6′ positions

Reaction of 6,6′-di- O-tosylsucrose hexa-acetate ( 1) with sodium chloride in hexamethylphosphoric triamide gave a mixture containing preponderantly the hexa-acetates of 6,6′-dichloro-6,6′-dideoxysucrose ( 2) and 6-chloro-6-deoxy-6′- O-tosyl-sucrose ( 3). Reaction of 3 with sodium benzoate in (Me 2N) 3PO gave the 6-chloro-6-deoxy-6′- O-benzoyl derivative 4. Subsequent O-de-esterification afforded syrupy 6-chloro-6-deoxysucrose ( 5), which gave a crystalline heptamethanesulphonate. The chloro groups in the heptabenzoate 7 and the hexa-acetate 2 were replaced by azide in (Me 2N) 3PO to give the corresponding derivatives of 6-azido-6-deoxysucrose ( 12) and 6,6′-diazido-6,6′-dideoxysucrose ( 8), respectively. O-De-esterification of the hexa-acetates 2 and 8 yielded the parent 6,6′-dichloride 6 and 6,6′-diazide 9, respectively. 6,6′-Di- O-tosylsucrose hexabenzoate ( 10) reacted with sodium bromide in (Me 2N) 3PO to give the 6,6′-dibromide 11, in high yield, which afforded 6-deoxy-β- D- xylo-hex-5-enopyranosyl 6′-deoxy-β- D- threo-hex-5′-enofuranoside hexabenzoate on treatment with silver fluoride in pyridine.

Studies on Aminosugars. XXXII. Synthesis of 3′, 4′-Dideoxykanamycin B

Abstract Penta-N-ethoxycarbonylkanamycin B (1) prepared from kanamycin B was treated with 2,2-dimethoxypropane in DMF to give a 3′,4′;4″,6″-di-O-isopropylidene derivative (3). Subsequent benzoylation afforded a 2″-O-benzoyl derivative (4), Removal of the isopropylidene groups from 4 followed by controlled isopropylidenation afforded the corresponding 4″,6″-O-isopropylidene derivative (5), which was then transformed to a 3′,4′-di-O-mesyl derivative (6). Treatment of 6 with sodium iodide and zinc dust in DMF gave the desired 3′,4′-unsaturated derivative (7). Hydrogenation and removal of the protecting groups gave the title compound. The 3′,4′-dideoxykanamycin B expectedly showed remarkable activity against kanamycin-resistant bacteria as well as sensitive strains.

Benzoyl derivatives of d-gluconolactones and their reaction with alcohols

Benzoylation of d-glucono-1,4-lactone and d-glucono-1,5-lactone afforded the corresponding tetra- O-benzoyl derivatives. They showed the optical rotation and i.r. spectral absorption characteristic for 1,4 or 1,5-lactones, respectively. Opening of the lactone ring was effected by treatment with alcohols to give tetra- O-benzoyl- d-gluconates having an unesterified hydroxyl group at C-4 or C-5, respectively.

Flourocarbohydrates : Part XVIII. 9-(3-deoxy-3-flouro-β- D-xylofuranosyl)adenine and 9-(3-deoxy-3-flouro-α- D-arabinofuranosyl)adenine

An alternative synthesis of 3-deoxy-3-fluoro-α- D-xylose ( 4a) from methyl 2,3-anhydro-5- O-benzyl-β- D-ribofuranoside ( 1) is described. Methyl 5- O-benzyl-3-deoxy-3-fluoro-β- D-xylofuranoside ( 3) and methyl 5- O-benzyl-3-deoxy-3-fluoro-α- D-arabinofuranoside ( 11) were converted, via the 2,5-di- O-benzoyl derivatives ( 6) and ( 12), into the correspondingαβ- D-glycosyl bromides ( 7) and ( 13). The latter compounds were then condensed with 6-benzamidopurine to yield the fluorinated nucleosides, 6-benzamido-9-(2,5-di- O-benzoyl-3-deoxy-3-fluoro-β- D-xylofuranosyl)purine ( 8) and 6-benzamido-9-(2,5-di- O-benzoyl-3-deoxy-3-fluoro-α- D-arabinofuranosyl)purine ( 14), respectively. Structural assignments of the fluoronucleosides ( 8) and ( 14) were based upon u.v. comparison with known 9-(3-deoxy-β- D-pentofuranosyl)adenines, and the fact that, on alkaline hydrolysis, compounds 8 and 14 yielded crystalline fluoronucleosides ( 9) and ( 15) which gave the 5′-toluene- p-sulphonates 10 and 16; on heating, compound 10 formed a 3,5′-cyclic p-toluenesulphonate, whereas compound 16 did not. These results are consistent with the anomeric configuration assigned to 9-(3-deoxy-3-fluoro-β- D-xylofuranosyl)adenine ( 9) and 9-(3-deoxy-3-fluoro-α- D-arabinofuranosyl)adenine ( 15). This synthesis of deoxyfluoronucleosides is considered to be less limited in application than those so far reported.

Reaction of ammonia with acylated aldoheptoses : Derivatives of D- glycero- D- gulo-heptose, D-glycero- L- manno-heptose, and D- glycero- D- galacto-heptose

The reaction of methanolic ammonia with the hexa- O-acetyl and hexa- O-benzoyl derivatives of D- glycero- D- gulo-heptose, D- glycero- L- manno-heptose, and D- glycero- D- galacto-heptose affords the 1,1-bis(acylamido)-1-deoxy- D-heptitols (2,3), from which the acetates have been prepared. The yields of 2 and 3 are in general higher than those of the corresponding hexose derivatives. On ammonolysis of hexa- O-benzoyl- D- glycero- L- manno-heptose, an N-benzoyl- D- glycero- L- manno-heptosylamine is formed, together with the main product.

Further observations on the antiscorbutic activity of O-benzoyl derivatives of L-ascorbic acid in guinea pigs.

Further observations on the antiscorbutic activity of O-benzoyl derivatives of L-ascorbic acid in guinea pigs.

Synthesis of L-Ascorbic Acid Acyl Derivatives stabilized against Oxidation

Benzoylation of the enediol system of L-ascorbic acid and 5, 6-isopropylidene-L-ascorbic acid have been investigated with the aim of obtaining O-benzoyl derivatives of L-ascorbic acid stabilized against oxidation. 2-O-benzoyl-L-ascorbic acid, 3-O-benzoyl-5, 6-isopropylidene-L-ascorbic acid, 2, 6-di-O-benzoyl-L-ascorbic acid, 3, 6-di-O-benzoyl-L-ascorbic acid and 3, 5, 6-tri-O-benzoyl-L-ascorbic acid have been prepared by making choice of suitable reaction conditions, especially of the mole ratios of the three reagents i.e.L-ascorbic acid or its isopropylidene homologues, benzoyl chloride and base. The structure of the products were determined on the basis of elementary analyses. IR and NMR data supplemented by UV spectra and PK values.