Branched-chain derivatives of acyclic adenosine analogs: Alkyl and hydroxymethyl derivatives of S-adenosyl-L-homocysteinase inhibitors substituted at the 2- and 3-position of the side chain

1989 ◽  
Vol 54 (1) ◽  
pp. 248-265
Author(s):  
Antonín Holý
Keyword(s):  
Acid Hydrolysis ◽  
Sodium Borohydride ◽  
Sodium Salt ◽  
Osmium Tetroxide ◽  
Sodium Perchlorate ◽  
Side Chain ◽  
Isopropylidene Derivative ◽  
Branched Chain ◽  
Hydrolysis Of ◽  
Derivatives Of

Reaction of 1,3-dichloro-2-propanone (VII) with methylmagnesium chloride, followed by alkaline hydrolysis, afforded 2-methylpropane-1,2,3-triol (VIII) which on treatment with 2,2-dimethoxypropane and subsequent tosylation gave 4-(p-toluenesulfonyloxymethyl)-2,2,4-trimethyl-1,3-dioxolane (IXb). Compound IXb was condensed with sodium salt of adenine and the intermediate X was acid-hydrolysed to give 9-(RS)-(2,3-dihydroxy-2-methylpropyl)adenine (XI). Oxidation of XI with sodium periodate led to 9-(2-oxopropyl)adenine (XII). 9-(RS)-(2-Hydroxy-2-hydroxymethyloctyl)adenine (XVI) was obtained analogously from compound VII and hexylmagnesium bromide via triol XIV. Methyl 2-bromomethyl-2-propenoate (XVII) reacted with sodium salt of adenine and the resulting methyl 2-(adenin-9-ylmethyl)-2-propenoate (XVIII) was hydroxylated with sodium perchlorate and osmium tetroxide. The obtained methyl (RS)-2-(adenin-9-ylmethyl)-2,3-dihydroxypropanoate (XIX) was alkali-hydrolysed to give sodium salt of the acid XX. Reduction of ester XIX with sodium borohydride furnished 9-(RS)-(2,3-dihydroxy-2-hydroxymethylpropyl)adenine (XXI). 1-Nonen-3-ol (XXIII), obtained by reaction of propenal with hexylmagnesium bromide, was converted by hydroxylation with osmium tetroxide into nonane-1,2,3-triol (XXIVa) and further into its 1-O-p-toluenesulfonate XXIVb which reacted with 2,2-dimethoxypropane to give 2,2-dimethyl-4-hexyl-5-(p-toluenesulfonyloxymethyl)-1,3-dioxolane (XXV). Compound XXV reacted with adenine and the resulting intermediate XXVI was converted into 9-(RS)-(2,3-dihydroxynonyl)adenine (XXVII) by acid hydrolysis. 9-(3-Methyl-2-buten-1-yl)adenine (XXVIII), obtained by alkylation of sodium salt of adenine with 1-bromo-3-methyl-2-butene, was oxidized with potassium permanganate in an acid medium to give 9-(3-hydroxy-2-oxo-3-methylbutyl)adenine (XXIX). This compound was converted into 9-(RS)-(2,3-dihydroxy-3-methylbutyl)adenine (XXX) by reduction with sodium borohydride. 4-C-Hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose (XXXII) reacted with 2,2-dimethoxypropane under formation of 4-C-hydroxymethyl-1,2:3,5-di-O-isopropylidene derivative XXXIIIa whose p-toluenesulfonyl derivative XXXIIIb on treatment with adenine afforded 4-C-(adenin-9-yl)methyl-1,2:3,5-di-O-isopropylidene-α-D-xylofuranose (XXXIV). Acid hydrolysis of this compound, followed by oxidation in an alkaline medium, gave (2S,3R)-4-(adenin-9-yl)-3-hydroxymethyl-2,3-dihydroxybutanoic acid, isolated as its ethyl ester XXXVI.

Stereospecific synthesis of isomeric 4-substituted 9-(2,3-dihydroxybutyl)adenines

1982 ◽  
Vol 47 (1) ◽  
pp. 173-189 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Acid Hydrolysis ◽  
Sodium Borohydride ◽  
Sodium Salt ◽  
Catalytic Hydrogenation ◽  
Sodium Azide ◽  
Sodium Iodide ◽  
Stereospecific Synthesis ◽  
Isopropylidene Derivative

Reduction of ethyl 2,3-O-isopropylidene-D-tartrate with sodium borohydride afforded (4S, 5S)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (Va) which was benzoylated to give monobenzoyl derivative Vd and further transformed into p-toluensulfonyl derivative Ve. Reaction of the compound Ve with sodium salt of adenine followed by methanolysis gave 2,3-O-isopropylidene derivative Vf which on acid hydrolysis afforded 9-(2S, 3S)-(2,3,4-trihydroxybutyl)adenine (Ia). The enantiomer IIa was obtained from 3,4-O-isopropylidene-D-mannitol via (4R, 5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (VIa) using the same procedure. Reaction of compounds Vf and VIf with p-toluenesulfonyl chloride afforded 4-O-p-toluenesulfonyl derivatives Vg and VIg. These compounds were also obtained from Va and VIa via di-p-toluenesulfonyl derivatives Vc and VIc by reaction with sodium salt of adenine. Treatment of compounds Vg and VIg with sodium iodide gave 4-iodo derivatives Vh and VIh which on reaction with tri-n-butyltin hydride, followed by acid hydrolysis, afforded enantiomeric threo-2,3-dihydroxybutyl derivatives Ib andIIb. Compounds Vg and VIg on treatment with sodium azide, subsequent catalytic hydrogenation of the intermediates Vj and VIj and acid hydrolysis afforded enantiomeric threo-9-(4-amino-2,3-dihydroxybutyl)adenines (Ic,IIc).

Synthesis and antiviral activity of stereoisomeric eritadenines

1982 ◽  
Vol 47 (5) ◽  
pp. 1392-1407 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Votruba ◽  
Erik De Clercq
Keyword(s):  
Antiviral Activity ◽  
Acid Hydrolysis ◽  
Vesicular Stomatitis Virus ◽  
Sodium Borohydride ◽  
Osmium Tetroxide ◽  
Sodium Periodate ◽  
Parainfluenza Virus ◽  
Racemic Mixture ◽  
Isopropylidene Derivative ◽  
Vesicular Stomatitis

D-Eritadenine (Ia) and L-eritadenine (IIa) were prepared from 5-(adenin-9-yl)-5-deoxyaldofuranoses or enantiomeric 2,3-disubstituted erythronolactones (VIIIb, c, XIV). Oxidation of methyl 2,3-O-isopropylidene-D-ribofuranoside (IX) with periodate in the presence of ruthenium, followed by acid hydrolysis and reduction with sodium borohydride, afforded L-ribonolactone (XI). Its 2,3-O-isopropylidene derivative was subjected to alkaline hydrolysis, followed by oxidation with periodate, reduction with sodium borohydride and reaction with cyclohexanone to give 2,3-O-cyclohexylidene-L-erythronolactone (XIV). Condensation of [U-14C]-adenine with VIIIb, followed by acid hydrolysis, afforded [U-14C-adenine]-D-eritadenine. The threo-eritadenines III and IV were prepared by oxidation of 1-(adenin-9-yl)-1-deoxy-2,3-O-isopropylidenethreitols XVI and XVII with sodium periodate in the presence of ruthenium, followed by acid hydrolysis. Reaction of 9-(2,2-diethoxyethyl)adenine (XIX) with malonic acid gave 4-(adenin-9-yl)-3-butenoic acid (XXI); its methyl ester XXII, prepared by treatment with methanol, was isomerized with triethylamine to give methyl 4-(adenin-9-yl)-2-butenoate (XXIII). Hydroxylation of XXIII with osmium tetroxide afforded the racemic mixture of D- and L-threo-eritadenine (III+ IV). Eritadenines Ia and IIa were active against vaccinia, measles and vesicular stomatitis virus. Eritadenine Ia was also effective against reo- and parainfluenza virus. In general, the antiviral activity of the eritadenines decreased in the order D-erythro (Ia) > L-erythro (IIa) > D- and L-threo (III, IV).

Preparation of enantiomeric and racemic 2,3,4,5-tetrahydroxypentyl derivatives of adenine, cytosine and uracil

1982 ◽  
Vol 47 (10) ◽  
pp. 2786-2805 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Acid Hydrolysis ◽  
Sodium Borohydride ◽  
Catalytic Hydrogenation ◽  
Protecting Groups ◽  
Sodium Salts ◽  
Hydrolysis Of ◽  
Derivatives Of ◽  
Subsequent Acid

1-(Adenin-9-yl)-1-deoxy-DL-ribitol (III), -D-arabitol (IXa), -L-arabitol (XIVa), -DL-xylitol (XXIVa), 1-(cytosin-L-yl)-1-deoxy-D-arabitol (IXb), -L-arabitol (XIVb), 1-(uracil-1-yl)-1-deoxy-D-arabitol (IXc), -L-arabitol (XIVc) and -DL-xylitol (XXIVb) were prepared by reaction of 1-O-p-toluenesulfonyl-2,3:4,5-di-O-isopropylidenealditols Ib, VIIb, XIIb and XXIIb with sodium salts of adenine, N4-benzoylcytosine or 4-methoxy-2-pyrimidone followed by removal of the protecting groups. Condensation of the mentioned sodium salts with methyl 5-O-p-toluenesulfonyl-2,3-O-isopropylidene-β-D-ribofuranoside (IV) with subsequent acid hydrolysis and reduction with sodium borohydride afforded 1-(adenin-9-yl)-1-deoxy-L-ribitol (VIa) and 1-(cytosin-1-yl)-1-deoxy-L-ribitol (VIb). 1-(Adenin-9-yl)-1-deoxy-L-lyxitol (XVII), -L-lyxitol (XVIII) and -2-O-methyl-D-lyxitol (XXI) were prepared analogously. Acid hydrolysis of 5-(adenin-9-yl)-5-deoxy-4-O-benzyl-1,2-O-isopropylidene-α-D-xylofuranose (XXVa), followed by reduction with sodium borohydride and catalytic hydrogenation, gave 1-(adenin-9-yl)-1-deoxy-L-xylitol (XXVIb).

1'-Derivatives of sucrose and their acid hydrolysis

1980 ◽  
Vol 33 (11) ◽  
pp. 2487 ◽  
Author(s):  
RD Guthrie ◽  
ID Jenkins ◽  
JJ Watters
Keyword(s):  
Acid Hydrolysis ◽  
Hydrolysis Of ◽  
Derivatives Of

Syntheses of 1'-chloro-1'-deoxy- and 1'-deoxy-sucrose are described. Several routes were investigated, the most successful being through 6,1',6'-tri-O-(2,4,6-trimethylbenzenesulfonyl)sucrose. Attempts to prepare 1'-deoxy-1'-fluorosucrose were unsuccessful. The rates of the acid-catalysed hydrolysis of 1'-chloro-1'-deoxysucrose and of 1'- deoxysucrose have been measured. These values are compared with that for sucrose itself. The mechanism of the hydrolyses is discussed.

ChemInform Abstract: KINETICS OF THE ACID HYDROLYSIS OF VINYL DERIVATIVES OF BENZIMIDAZOLE-2-THIONE, BENZOXAZOL-2-ONE AND -2-THIONE

1983 ◽  
Vol 14 (17) ◽  
Author(s):  
L. I. SVYATKINA ◽  
N. D. ABRAMOVA ◽  
L. L. DMITRIEVA ◽  
B. V. TRZHTSINSKAYA ◽  
G. G. SKVORTSOVA
Keyword(s):  
Acid Hydrolysis ◽  
Vinyl Derivatives ◽  
Kinetics Of ◽  
Hydrolysis Of ◽  
Derivatives Of

Acid hydrolysis of N-methyl derivatives of 4-phenyl-5-oxo-4,5-dehydroindeno[1,2-b]pyridine

1986 ◽  
Vol 22 (10) ◽  
pp. 1104-1107 ◽  
Author(s):  
V. K. Lusis ◽  
D. Kh. Mutsenietse ◽  
G. Ya. Dubur
Keyword(s):  
Acid Hydrolysis ◽  
Methyl Derivatives ◽  
Hydrolysis Of ◽  
Derivatives Of

The synthesis and the pharmacological properties of enantiomeric derivatives of 7-(2,3-dihydroxypropyl)theophylline

1979 ◽  
Vol 44 (8) ◽  
pp. 2550-2555 ◽  
Author(s):  
Antonín Holý ◽  
Miroslav Vaněček
Keyword(s):  
Guinea Pig ◽  
Acid Hydrolysis ◽  
Sodium Salt ◽  
Blood Circulation ◽  
Pharmacological Properties ◽  
Camp Phosphodiesterase ◽  
Derivatives Of ◽  
Subsequent Acid

7-(S)-(2,3-Dihydroxypropyl)theophylline ((S)-I) and its enantiomer (R)-I were prepared by heating of the sodium salt of theophylline with 1-O-toluenesulfonyl-2,3-O-isopropylidene-D-glycerol or its L-enantiomer and subsequent acid hydrolysis. The two enantiomers I do not differ either by the inhibition of 3',5'-cAMP-phosphodiesterase, vasodilatatory activity on isolated guinea-pig aorta, or the effect on blood circulation of dogs in vivo.

Synthesis of 3-(5-Alkyl-4-acetyl(ethoxycarbonyl))-2-propenoates from Derivatives of 3-Phenoxy-2-furylmethylene

1992 ◽  
Vol 57 (8) ◽  
pp. 1684-1692 ◽  
Author(s):  
Štefan Marchalín ◽  
Vladimír Mlynárik ◽  
Anna Staňová ◽  
Dušan Ilavský
Keyword(s):  
Acid Hydrolysis ◽  
Hydrogen Chloride ◽  
Pure Form ◽  
Geometric Isomers ◽  
Transition Mechanism ◽  
One Step ◽  
Hydrolysis Of ◽  
Derivatives Of ◽  
Trisubstituted Furans

3-(2-Furyl)propenoates IV-VIII were obtained by treatment of 5-phenoxy-2-furylmethylene derivatives I-III with alcoholic hydrogen chloride in one step. The probable transition mechanism of synthons I-III into the 2,4,5-trisubstituted furans is presented. The geometric isomers E-IV, Z-V and Z-VI, isolated in pure form, were transformed into the corresponding acids E-IX, Z-IX and E-X by base-catalyzed hydrolysis. Acid hydrolysis of the 1,3-diketone I afforded (4Z,6Z)-6-acetyl-7-hydroxy-2,4,6-octatrien-4-olide (XI). Structure of the products was verified by spectral (IR, UV, NMR and mass) methods.

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