92924-62-4Relevant articles and documents
Microwave-assisted hydrolysis of phosphonate diesters: An efficient protocol for the preparation of phosphonic acids
Jansa, Petr,Baszczynski, Ondrej,Prochazkova, Eliska,Dracinsky, Martin,Janeba, Zlatko
, p. 2282 - 2288 (2012)
A new highly efficient method for the hydrolysis of acyclic nucleoside phosphonate diesters (or generally of any organophosphonates) to the corresponding phosphonic acids has been developed. This novel methodology employs inexpensive hydrochloric acid in equimolar amounts to the number of ester groups present in the molecule and thus, avoids using trimethylsilyl halogenides, the standard reagents for these types of transformations. Moreover, simple and easy work-up of the reaction mixture affords very clean products in high yields (usually 77-93%). Another advantage of the described hydrolysis of phosphonate diesters is the fact that the course of the reaction can be instantly monitored through pressure changes in the reaction vessel. This 'green' method has also been successfully used for the preparation of otherwise synthetically difficult to access (phosphonomethoxy)ethyl (PME) derivatives of guanine (PMEG) and hypoxanthine (PMEHx), and furthermore, the method gains access to important novel acyclic nucleoside phosphonates derived from 2-chlorohypoxanthine and from xanthine (e.g. PMEX).
SYNTHESES OF ENANTIOMERIC N-(3-HYDROXY-2-PHOSPHONOMETHOXYPROPYL)DERIVATIVES OF PURINE AND PYRIMIDINE BASES
Holy, Antonin
, p. 649 - 674 (2007/10/02)
Methods of preparation of N-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) derivatives of (2S)- and (2R)-configuration compounds I and XXVII, respectively are described.The general method starts from the corresponding N-(2,3-dihydroxypropyl) derivatives which were converted either into the (R)-enantiomers XIII by reaction of the base with (R)-glycidol butyrate (XII) in the presence of cesium carbonate and subsequent methanolysis, or into the (S)-enantiomers XI by alkylation of the base with (R)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (V) in the presence of the same reagent.The amino groups on the heterocyclic base in compounds XI and XIII were benzoylated by silylation followed by reaction with benzoyl chloride and the obtained N-benzoates XV and XVII on reaction with trityl chloride afforded the corresponding 3'-O-trityl derivatives XVI and XVIII.These compounds were condensed with bis(2-propyl)-p-toluenesulfonyloxymethanephosphonate (XXIII) in dimethylformamide in the presence of sodium hydride to give the fully protected diesters XXIV and XXVIII.These compounds could be selectively acid-hydrolyzed to remove the trityl group only under formation of compounds XXXV, or methanolyzed and then acid-hydrolyzed to remove the trityl and N-benzoyl groups and lead to compounds XXVI and XXX, or treated with bromotrimethylsilane to remove the trityl and 2-propyl group to give phosphonates of the type XXVI.All the three types of compounds were then converted into free phosphonates of the (S)-series (I) and (R)-series (XXVII).Derivatives of cytosine (Ia, XXVIIa), adenine (Ib, XXVIIb), 2,6-diaminopurine (Ic, XXVIIc) and guanine (Id, XXVIId) were prepared.Condensation of the partially blocked adenine derivative XXXV with the tosyl derivative XXIII and subsequent deprotection afforded 9-(S)-(2,3-diphosphonomethoxypropyl)adenine (XLIII).Reaction of the same compound XXXV or its (R)-enantiomer XXXVIII with diethyl chlorophosphonate, followed by deblocking, afforded 3'-O-phosphoryl derivatives (S)-HPMPA (XXXVII) and (R)-HPMPA (XL).
Synthesis of purin-9-ylalkylenoxymethyl phosphonic acids
-
, (2008/06/13)
An improved process for the preparation of purin--9-ylalkylenoxymethyl phosphonic acids, novel nucleotide analogs, typified by (S)-9-(3-hydroxy-2-phosphonylmethoxy-propyl)adenine, also known as (S)-HPMPA. The improved process employs novel intermediates, is shorter and more efficient by virtue of eliminating large scale isomer separations and ion exchange chromatography, and also is applicable to guanine derivatives as well as to adenine derivatives.
