Synthesis of N-(3-Azido-2-hydroxypropyl), N-(3-Phthalimido-2-hydroxypropyl) and N-(3-Amino-2-hydroxypropyl) Derivatives of Heterocyclic Bases

1994 ◽  
Vol 59 (5) ◽  
pp. 1153-1174 ◽  
Author(s):  
Maria Spassova ◽  
Hana Dvořáková ◽  
Antonín Holý ◽  
Miloš Buděšínský ◽  
Milena Masojídková
Keyword(s):  
Aqueous Medium ◽  
Cesium Carbonate ◽  
Subsequent Reaction ◽  
Weakly Alkaline ◽  
Basic Catalysis ◽  
Palladium On Carbon ◽  
Heterocyclic Bases ◽  
Derivatives Of

Alkylation of heterocyclic bases with azidomethyloxirane (I) under basic catalysis with potassium or cesium carbonate afforded N-(3-azido-2-hydroxypropyl) derivatives II. Hydrogenation of these compounds over palladium on carbon gave the corresponding 3-amino-2-hydroxypropyl derivatives III. The same compounds III were prepared by alkylation of heterocyclic bases with phthalimidomethyloxirane (VII) in the presence of cesium carbonate and subsequent reaction of the formed N-(3-phthalimido-2-hydroxypropyl) derivatives VIII with hydrazine. The phthalimido derivatives VIII are easily hydrolyzed already in weakly alkaline aqueous medium to give 9-[3-(o-carboxybenzoylamino)-2-hydroxypropyl] derivatives IX and X.

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.

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).

Binding of calcium and lead ions to carboxystarch prepared by action of nitrogen dioxide on native starch and its 2,3-dialdehyde derivatives

1986 ◽  
Vol 51 (6) ◽  
pp. 1340-1351 ◽  
Author(s):  
Rudolf Kohn ◽  
Karol Tihlárik
Keyword(s):  
Nitrogen Dioxide ◽  
Alkaline Medium ◽  
Binding Capacity ◽  
Lead Ions ◽  
Carbonyl Groups ◽  
Weakly Alkaline ◽  
Exchange Cations ◽  
Counter Ions ◽  
The Stability ◽  
Derivatives Of

The binding of calcium and lead ions to carboxy derivatives of starch prepared by allowing nitrogen dioxide to act on native maize starch (procedure A) and on starch 2,3-dialdehyde derivatives of degrees of oxidation DO(d.a.) ≥ 0.94 (procedure B) was studied. The carboxy group content of the samples in the H+ form was 4.6 - 12.1 mmol g-1. The effect of alkaline medium on the stability of the carboxy derivatives and on their ability to bind and exchange cations was examined. The Ca2+ → 2K+ exchange was evaluated in terms of the decrease in the electrostatic free enthalpy Δ(Gel/N)KCa, determined by alkalimetric potentiometric titrations, and the binding of Pb2+ ions was evaluated in terms of the activity of the Pb2+ counter-ions determined in suspensions of Pb salts of the carboxy derivatives by means of an ion specific electrode. The IR and CD spectra revealed that the carboxystarch preparations obtained by procedure A contained, in addition to free carboxy groups, a considerable amount of carbonyl groups. During the conversion of the latter groups to the former, even in a weakly alkaline medium, the carboxy derivatives undergo an appreciable degradation and lose, to a great extent, their ability to bind and exchange cations. Procedure B, on the other hand, leads to highly selective starch and amylose carboxy derivatives, exhibiting a small amount of carbonyl groups and featuring a relative stability towards alkaline medium; their binding capacity is as high as 12 milliequivalents of cations per g of sample.

1-Substitution derivatives of 4-aryl-2,3-dibromo-1-naphthol

1981 ◽  
Vol 46 (9) ◽  
pp. 2116-2122 ◽  
Author(s):  
Jiří Křepelka ◽  
Jiří Roubík ◽  
Jiří Holubek
Keyword(s):  
Aqueous Medium ◽  
Ethyl Esters ◽  
Derivatives Of

Alkylation of 7-ethyl-4-(4-ethylphenyl)-2,3-dibromo-1-naphthol (I) with ethyl esters of ω-bromoalkanoic acids XX-XXIII in a non-aqueous medium gave the 1-substitution derivatives II, IV, VI and VIII which were hydrolyzed to the acids III, V, VII and IX. The acid III was used for syntheses of the esters X-XIII and amides XIV-XVIII. Compounds II-XVIII exhibited moderate antineoplastic effects in animals with transplanted tumours; best results were observed with the compound II.

The melanocyte stimulating activity of N-nitroso-2-chloroethyl-carbamoyl derivatives of α-melanotropin fragments

1988 ◽  
Vol 53 (11) ◽  
pp. 2574-2582 ◽  
Author(s):  
Hedvig Medzihradszky-Schweiger ◽  
Helga Süli-Vargha ◽  
József Bódi ◽  
Kálmán Medzihradszky
Keyword(s):  
Biological Activity ◽  
Active Site ◽  
Frog Skin ◽  
Terminal Sequence ◽  
Subsequent Reaction ◽  
Affinity Labels ◽  
Derivatives Of

A number of N-nitroso-2-chloroethyl-carbamoyl (Q(NO)) derivatives of α-melanotropin fragments have been synthesized and their effect on the frog skin melanocytes studied. Peptides substituted in this way possess the biological activity of the parent compounds, indicating that they preserved their receptor recognizing ability. These compounds can therefore serve as affinity labels. Some of these derivatives, related to the C-terminal sequence of α-melanotropin show prolonged darkening reaction, which does not influence the subsequent reaction of melanocytes with α-melanotropin. The Q(NO)-derivative of a fragment derived from the classical active site of the hormone shows, however, inhibition of the effect of α-melanotropin. It can be concluded that the latter peptide acts through the melanotropin receptor, while others, related to the C-terminal sequence of the hormone through another mechanism.

Silyl Derivatives of the Mixed Sandwiches Cyclopentadienyl Manganese Benzene and Cyclopentadienyl Manganese Biphenyl, CpMn(C6H6) and CpMn(C6H5-Ph)

1997 ◽  
Vol 52 (9) ◽  
pp. 1037-1042 ◽  
Author(s):  
Max Herberhold ◽  
Thomas Hofmann ◽  
Stefanie Weinberger ◽  
Bernd Wrackmeyer
Keyword(s):  
Nmr Spectroscopy ◽  
Membered Ring ◽  
Grignard Reagents ◽  
Sandwich Complexes ◽  
Subsequent Reaction ◽  
Silyl Derivatives ◽  
Magnesium Halide ◽  
Derivatives Of

Mixed manganese sandwich complexes containing a silyl-substituted cyclopentadienyl ring, e. g. (η5 - C5H4 - R)Mn(η6- C6H6) (3a - c) and (η5- C5H4 - R)Mn(η6- C6H5 - Ph) (4a - c); (R = SiMe3 (a), Si2Me5 (b) and SiMe2tBu (c)), were obtained in low yield via intermediates {(η5 - C5H4 - R)MnCl} and their reaction with phenyl Grignard reagents. Use of the 4-trimethylsilyl-phenyl magnesium halide in the reaction with the intermediate {CpMnCl} led to complexes with silylsubstituted arene rings, CpMn(η6 - C6H5 - R′) (5a) and CpMn(η6 -R′ - C6H5 - C6H5 - R′) (6a); (R′ = SiMe3 (a)). Dilithiation of CpMn6H6) (1) and subsequent reaction with a chlorosilane gave (η5-C5H4 - R)Mn(η6 - C6H5 - R′) (7a,b); (R = R′ = SiMe3 (a), Si2Me5 (b)). A cyclophane 8 in which five- and six-membered ring are linked through a -Me2Si-SiMe2- bridge was obtained using 1,2-dichloro-tetramethyldisilane. The mixed manganese sandw ich complexes were thoroughly characterized by 1H , 13C, 29Si and 55Mn NMR spectroscopy. The 55Mn spectra can be used to detect low-yield side-products.

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.

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