Synthesis of new mono- and disubstituted hydroxyalkyl and aminoalkyl derivatives of heterocyclic bases

1978 ◽  
Vol 43 (12) ◽  
pp. 3444-3465 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Heterocyclic Bases ◽  
Derivatives Of

Synthesis and Biological Effects of N-(2-Phosphonomethoxyethyl) Derivatives of Deazapurine Bases

1993 ◽  
Vol 58 (6) ◽  
pp. 1419-1429 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý
Keyword(s):  
Biological Effects ◽  
Sodium Hydride ◽  
Cesium Carbonate ◽  
Cytostatic Effect ◽  
Phosphonic Acids ◽  
Dna Viruses ◽  
Purine Bases ◽  
Heterocyclic Bases ◽  
L 1210 Leukemia ◽  
Derivatives Of

Analogs of antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA,II), containing modified purine bases 1-deazaadenine (VII, 3-deazapurine (XI), 7-deaza-7-cyanoadenine (XIIIb) and 3-deazaguanine (XXIb) were prepared by alkylation of the heterocyclic bases with bis(2-propyl) 2-chloroethoxymethylphosphonate (V) in dimethylformamide in the presence of sodium hydride or cesium carbonate. The obtained protected derivatives were deblocked with bromotrimethylsilane to give the phosphonic acids. 3-DeazaPMEG (XXIb) is active against DNA viruses and exhibits a marked cytostatic effect against L-1210 leukemia.

Synthesis of 2-Deoxy-β-D-ribonucleosides and 2,3-Dideoxy-β-D-pentofuranosides on Immobilized Bacterial Cells

1994 ◽  
Vol 59 (10) ◽  
pp. 2303-2330 ◽  
Author(s):  
Ivan Votruba ◽  
Antonín Holý ◽  
Hana Dvořáková ◽  
Jaroslav Günter ◽  
Dana Hocková ◽  
...  
Keyword(s):  
The Other ◽  
Bacterial Cells ◽  
Amino Groups ◽  
E Coli ◽  
Pyrimidine Series ◽  
Acceptor Activity ◽  
Dependent Strain ◽  
Pyrimidine Bases ◽  
Heterocyclic Bases ◽  
Derivatives Of

Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs. All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N9-isomers in the purine and N1-isomers in the pyrimidine series. Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety. The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N7-nitrogen atom. On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives. Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed. The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-dideoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-dideoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.

General Method of Preparation of N-[(S)-(3-Hydroxy-2-phosphonomethoxypropyl)] Derivatives of Heterocyclic Bases

1993 ◽  
Vol 58 (5) ◽  
pp. 1151-1163 ◽  
Author(s):  
Petr Alexander ◽  
Antonín Holý
Keyword(s):  
Sodium Salt ◽  
Boron Trifluoride ◽  
Boron Trifluoride Etherate ◽  
Cesium Carbonate ◽  
Analogous Reaction ◽  
Sodium Salts ◽  
Heterocyclic Bases ◽  
Derivatives Of ◽  
General Method ◽  
Methanolic Ammonia

Reaction of (R)-1-O-p-toluenesulfonyl-1,2,3-propanetriol (IV) with N-trimethylacetylimidazole (II) afforded (R)-1-O-p-toluenesulfonyl-3-O-trimethyacetyl-1,2,3-propanetriol (V) which was reacted with dimethoxymethane in the presence of phosphorus pentoxide to give (R)-2-O-methoxymethyl-1-O-p-toluenesulfonyl-3-O-trimethyacetyl-1,2,3-propanetriol (VI). Compound VI was treated with acetic anhydride and boron trifluoride etherate and the obtained 2-acetoxy derivative VII reacted with bromotrimethylsilane to give the intermediary bromomethyl ether VIII. Compound VIII on reaction with tris(2-propyl) phosphite afforded (R)-2-O-bis(2-propyl)phosphonomethyl-1-O-p-toluenesulfonyl-3-O-trimethyacetyl-1,2,3-propanetriol (IX). Condensation of synthon IX with sodium salts of adenine, 2,6-diaminopurine, or with cytosine, 6-azacytosine or 2-chloroadenine in the presence of cesium carbonate, afforded fully protected diesters X and XIIIb which on methanolysis and reaction with bromotrimethylsilane gave N-[(S)-(3-hydroxy-2-phosphonomethoxypropyl)] derivatives of adenine (XIa), 2- chloroadenine (XIb), 2,6-diaminopurine (XIc), cytosine (XIVa) and 6-azacytosine (XIVb). In an analogous reaction, sodium salt of 4-methoxy-2-pyrimidone reacted with compound IX to give an intermediate XIIIa which on treatment with methanolic ammonia and subsequent deblocking under the same conditions also afforded the cytosine derivative XIVa. Sodium salt of 2-amino-6-chloropurine was in this way converted into the corresponding 2-aminopurine derivative XVIII. Deprotection of this compound gave 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)-2-aminopurine (XIX).

Synthesis of N-(2-(2-phosphonylethoxy)ethyl) derivatives of heterocyclic bases

1990 ◽  
Vol 55 (3) ◽  
pp. 809-818 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Rosenberg ◽  
Hana Dvořáková
Keyword(s):  
Triethyl Phosphite ◽  
Sodium Salts ◽  
Subsequent Hydrolysis ◽  
Pyrimidine Bases ◽  
Heterocyclic Bases ◽  
Derivatives Of

Reaction of bis(2-chloroethyl) ether (II) with triethyl phosphite afforded diethyl 2-chloroethoxyethylphosphonate (III). This compound reacts with sodium salts of heterocyclic bases to give diethyl esters of N-(2-(2-phosphonylethoxy)ethyl) derivatives of purine and pyrimidine bases IV. Compounds IV on reaction with bromotrimethylsilane and subsequent hydrolysis were converted into N-(2-(phosphonylethoxy)ethyl) derivatives IV.

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