Patent ID: 6441161
Filing Date: 2002-08-27
Classification: C07H

Abstract:
A method for preparing modified nucleosides, comprising:a) reacting a nucleoside starting material having the following formula: with a vinylstannane of the formula (alkyl3Sn)(R8)C&boxH;C(R8)2 and carbon monoxide in the presence of a palladium catalyst to form an ene-one intermediate;b) reacting the ene-one intermediate with an amine of the formula HNR1R2 wherein: Lg is independently selected from the group consisting of H or a leaving group; R1 and R2 function to modulate, modify and/or control the biological activity of the compound and are independently selected from the group consisting of H, C1-C18 alkyl, alkenyl or alkynyl, phenyl, aralkyl, alkaryl, an alkanoic acid or its ester and amide derivatives, a peptide fragment, an HIV aspartyl protease inhibitor, groups that are cleaved intracellularly, and groups that increase the hydrophilicity, hydrophobicity, electrostatic capacity or hydrogen bonding capacity of the compound; R3, R4 and R5 are independently selected from the group consisting of H, â€”OH, protected oxy-, â€”NH2, F, â€”N3, â€”CN, â€”NC, â€”OAc, â€”SAc, â€”OBz, and â€”OSiR73, wherein R7 is C1-C4 alkyl or phenyl; R6 is selected from the group consisting ofâ€”OH, protected oxy-, phosphate, diphosphate, triphosphate, phosphate esters, phosphoramidites, phosphorothionates, and phosphorodithionates; R8 is independently selected from the group consisting of H, aryl, aralkyl, alkyl, alkaryl, alkenyl, alkynyl, alkoxy, and â€”C(O)â€”R9, where R9 is selected from the group consisting of H, alkyl, aryl, aralkyl, alkaryl and alkoxy; the protected oxy- groups of R4 and R5 taken together can represent an isopropylidene group (â€”OC(CH3)2Oâ€”) or an orthoformate group (â€”OCH(OR7)Oâ€”); and the protected oxy- groups of R5 and R6 taken together can represent a 3â€²,-5â€²-tetraalkyldisiloxane group (â€”OSi(alkyl)2OSi(alkyl)2Oâ€”); and c) isolating said modified nucleoside.