Synthesis of 9-(2-Phosphinomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (8) ◽  
pp. 1870-1878 ◽  
Author(s):  
Petr Alexander ◽  
Antonín Holý ◽  
Milena Masojídková
Keyword(s):  
Acid Hydrolysis ◽  
Phosphorus Atom ◽  
Amino Group ◽  
Protecting Group ◽  
Hydrolysis Of ◽  
Related Compounds

Alkyl 2-chloroethoxymethyl(diethoxymethyl)phosphinates VII and XIII were prepared by reaction of silyl esters of dialkoxymethylphosphinic acid with 2-chloroethyl chloromethyl ether. Adenine was alkylated with VII and XIII to give [2-(adenin-9-yl)ethoxy]methyl(diethoxymethyl)phosphinates VIII and XIV, bearing the dialkoxymethyl protecting group on the phosphorus atom. Acid hydrolysis of compounds VIII and XIV afforded 9-(2-phosphinoethoxymethyl)adenine (X). Alkyl dialkoxymethylphosphinates V and XI reacted with paraformaldehyde to give hydroxymethylphosphinates XV and XIX which were converted into the synthons XVI, XVII and XVIII capable of introducing a protected hydroxymethylphosphino group on a hydroxy or amino group.

Synthesis and acid hydrolysis of trans-dichlorobis(ethylenediamine)ruthenium(III) and related compounds

1975 ◽  
Vol 14 (10) ◽  
pp. 2575-2577 ◽  
Author(s):  
John A. Broomhead ◽  
Leon. Kane-Maguire ◽  
David. Wilson
Keyword(s):  
Acid Hydrolysis ◽  
Hydrolysis Of ◽  
Related Compounds

Antihistamine Substances. Tricyclic Analogues of N-(4,4-Diphenyl-3-butene-1-yl)nipecotic Acid and Some Related Compounds

1994 ◽  
Vol 59 (3) ◽  
pp. 667-674 ◽  
Author(s):  
Karel Šindelář ◽  
Alexandra Šilhánková ◽  
Jiří Urban ◽  
Jan Metyš ◽  
Martin Valchář ◽  
...  
Keyword(s):  
Acid Hydrolysis ◽  
Nipecotic Acid ◽  
Amino Esters ◽  
Hydrolysis Of ◽  
Related Compounds

Alkylation of ethyl nipecotate with bromides VII - X gave amino esters Ib - Vb. Alkylation of ethyl piperazine-2-carboxylate with 4-bromo-1,1-diphenyl-1-butene afforded compound Vb. Final product Ia - Va were obtained by acid hydrolysis of corresponding esters Ib - Vb. Some of the compounds showed significant antihistamine and antiulcer activities.

Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (9) ◽  
pp. 2069-2094 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Reaction Pathway ◽  
Sodium Hydride ◽  
Amino Group ◽  
Trimethylsilyl Derivative ◽  
Phosphonic Acids ◽  
Alkyl Derivatives ◽  
Hydrolysis Of ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of ◽  
Related Compounds

To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI. After protection of the adenine amino group by benzoylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with diisopropyl p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters XII were converted into phosphonic acids I by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives. The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 2,6-Diaminopurine derivatives XVIIId and XXIIb were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.

Sulfenyl Halides as Modifying Reagents for Polypeptides and Proteins

1968 ◽  
Vol 23 (10) ◽  
pp. 1319-1325 ◽  
Author(s):  
F. M. Veronese ◽  
A. Fontana ◽  
E. Boccu ◽  
C. A. Benassi
Keyword(s):  
Polypeptide Chain ◽  
Peptide Bond ◽  
Tryptophan Residue ◽  
Amino Group ◽  
Model Compounds ◽  
Mild Conditions ◽  
Selective Reaction ◽  
Hydrolysis Of ◽  
Related Compounds ◽  
Sulfenyl Halides

The conversion of 2-thio-aryl-tryptophan and related derivatives to the corresponding 2-hydroxycompounds by acidic hydrolysis was investigated. The thioether function is introduced into the tryptophan residue by the selective reaction of sulfenyl halides with the indole nucleus. The substitution occurs under mild conditions only when the amino group of the tryptophan residue is free. The assistance of the amino group was confirmed using model compounds. Thus 2-thio-(2-nitrophenyl) -tryptamine is smoothly converted to 2-hydroxy-tryptamine whereas 2-thio- (2-nitrophenyl) -β-indolyl-propionic acid is completely stable under the same conditions. The conversion of 2-thio-aryl-tryptophan units linked in a polypeptide chain to the corresponding 2-hydroxy-tryptophan occurs only under conditions during which hydrolysis of the peptide bond occurs. It was also observed that the 2-nitro-thiophenols which are released during the hydrolysis of 2-thio- (2-nitrophenyl) -tryptophan and related compounds are converted under the conditions of the reaction to 2-aminobenzene sulfonic acids.

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