Process for the preparation of nucleoside alkyl-aralkyl- and aryl-phosphonites and -phosphonates

A process for the preparation of deoxyribonucleoside phosphonates of the formula I ##STR24## in which T is a triphenylmethyl protecting group for a primary hydroxyl group;

• B is a deoxyribonucleoside base radical, wherein the groups B may be the same or different and are independently selected from the group consisting of 1-thyminyl, 1-(N-4protected)-cytosinyl, 9-(N-6-protected)-adeninyl and 9-(N-2-protected)-quaninyl;
• G is an acyl or silyl protecting group for a secondary hydroxyl group;
• Z is selected from the group consisting of oxygen, sulfur and selenium;
• and
• R is selected from the group consisting of an alkyl moiety having up to 8 C atoms, cyclohexyl, benzyl, phenyl and phenyl substituted by a member selected from the group consisting of fluorine, chlorine, bromine, lower alkyl, lower alkoxy and trifluoromethyl,
• which comprises reacting a difunctional phosphonylating reagent of the formula II ##STR25## wherein X is chlorine or Y, and Y is a group of the formula ##STR26## wherein R.sup.1 and R.sup.2, which are identical or different, are selected from the group consisting of alkyl having up to 8 C atoms and phenyl, or R.sup.1 and R.sup.2, together with the nitrogen, form a moiety selected from the group consisting of imidazolo, triazolo, nitrotriazolo and tetrazolo moieties, with a nucleoside of the formula III ##STR27## wherein T and B have the meanings given above, and reacting the resulting compound of the general formula IV ##STR28## with a compound of the formula V ##STR29## wherein B and G have the meanings given above, to form compounds of the formula VI ##STR30## wherein T, R, B and G have the meanings given above, and oxidatively converting said compounds of the formula VI to compounds of the formula I, wherein the intermediate products of the process do not spontaneously form significant amounts of symmetrical 3',3'- and 5',5'-products.