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Über die Synthese von 2′,3′‐Didesoxy‐3′‐(phosphonomethyl)nucleosiden, Phosphonat‐Analogen von 2′‐Desoxy‐3′‐nucleotiden
Author(s) -
Morr Michael,
Ernst Ludger,
Schomburg Dietmar
Publication year - 1991
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1991199101114
Subject(s) - chemistry , acetic anhydride , stereochemistry , isoindole , hydrazine (antidepressant) , pyridine , guanosine , medicinal chemistry , organic chemistry , catalysis , biochemistry , chromatography
Synthesis of 2′,3′‐Dideoxy‐3′‐(phosphonomethyl)nucleosides, Phosphonate Analogs of 2′‐Deoxy‐3′‐nucleotides 1,2‐Di‐ O ‐acetyl‐5‐ O ‐benzoyl‐3‐deoxy‐3‐(diethoxyphosphorylmethyl)‐β‐ D ‐ribofuranose ( 8 ) is linked (a) to the protected purine bases A Bz , G iB and T, respectively, in the presence of potassium nonaflate and (b) to the silylated pyrimidine bases C, U and U F (= 5‐fluoro‐U) according to the Hilbert‐Johnson method by using stannic tetrachloride. Selective 2′‐ O ‐deacetylation by hydroxylammonium acetate or hydrazine hydrate employing Ishido's procedure, followed by reaction with phenyl thionochlorocarbonate/4‐(dimethylamino)pyridine, furnishes thionocarbonates 14a–f . These are converted to the deoxy derivatives 15a–f with tributyltin hydride/azobis(isobutyronitrile). For the preparation of the free 2′‐deoxy‐3′‐phosphonic acids 18a–f a special strategy is developed. Hydrolysis of the phosphonic esters is carried out by using bromotrimethylsilane or iodotrimethylsilane, the latter being prepared in situ. 3′‐Deoxy‐3′‐(phosphonomethyl)guanosine ( 10b1 ) is described for the first time. The structures of the new compounds follow from their 1 H‐, 13 C‐ and 31 P‐NMR spectra. X‐ray structure analyses were carried out for 8 , for 9‐(5‐ O ‐benzoyl‐3‐deoxy‐3‐diethoxyphosphorylmethyl‐β‐ D ‐ribofuranosyl)‐6‐hydroxy‐2‐isobutyramidopurin ( 12b ) and its 2,3‐dideoxy analog 15b .