- Method for synthesizing antiviral drugs cidofovir and buciclovir
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The invention relates to a method for synthesizing antiviral drugs, i.e., cidofovir and buciclovir, belonging to the field of asymmetric synthesis in organic chemistry. According to the invention, pyrimidine with position 1 substituted by an allyl group or purine with position 9 substituted by a butenyl group are used as raw materials and subjected to asymmetric dihydroxylation so as to obtain a key chiral intermediate of cidofovir or buciclovir, and then a multi-step reaction is carried out so as to obtain cidofovir or buciclovir. With such a route in the invention, the reaction raw materialsare easily available, stereoselectivity is high, and the chiral dihydroxynucleoside intermediates are obtained after the reaction, and the cidofovir and buciclovir can be smoothly obtained after multiple steps of transformation.
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- CIDOFOVIR PEPTIDE CONJUGATES AS PRODRUGS
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Cidofovir-based compounds having an amino acid, dipeptide or tripeptide attached to a cidofovir or cyclic cidofovir framework. The compounds show enhanced oral bioavailability and increased binding to the PepT1 transporter. The present invention also provides compositions and methods for treating virus infections, and a method of preparing cidofovir.
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Page/Page column 11; figure 3
(2008/06/13)
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- A Practical Synthesis of (S)-HPMPC
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Synthesis of the title nucleotide was accomplished in high yield starting from (S)-tritylglycidol (5) and N-benzoylcytosine (9).
- Brodfuehrer, Paul R.,Howell, Henry G.,Sapino, Chester Jr.,Vemishetti, Purushotham
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p. 3243 - 3246
(2007/10/02)
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- SYNTHESES OF ENANTIOMERIC N-(3-HYDROXY-2-PHOSPHONOMETHOXYPROPYL)DERIVATIVES OF PURINE AND PYRIMIDINE BASES
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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).
- Holy, Antonin
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p. 649 - 674
(2007/10/02)
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