Several methods for the preparation of halogenated and alkylated methylenebisphosphonates have been examined. C-Alkyl chloromethylenebisphosphonates were prepared by dihalogenation of tetraisopropylmethylene- bisphosphonate with sodium hypochlorite and selective monodehalogenation with methyl lithium, followed by alkylation of the thallium(I) salt and deesterification with bromotrimethylsilane and water. Such compounds were shown to be inhibitors of influenza A/X49 RNA transcriptase activity, and to be significantly better inhibitors of the replication of the virus in cell cultrue than either PAA or any unalkylated bisphosphonates. The C-benzyl analogue was found to show no reduction in affinity for calcified tissue over the parent species. Using the synthetic methodology developed, an affinity label was prepared for the virus proteins. When this was incubated with the virus and reduced with [ɜH] -NaBH4, the three virus P proteins were radioactively labelled. Some simple nucleopeptides were prepared as models of the VPg-pU linkage in poliovirus vRNA. The compounds were best prepared via a phosphorus(III) route in analogy to the phosphite triester method of nucleotide synthesis.