Nucleotide coupling was investigated in reverse micelles formed by (ce
tyl)trimethylammonium bromide (CTAB), in hexane/pentan-1-ol. In partic
ular, the coupling of 2'-deoxy-5'-O-methylcytidine 3'-O-phosphate, pre
pared by phosphoramidite chemistry, with 5'-amino-5'-deoxythymidine wa
s studied in the presence of a H2O-soluble carbodiimide at w(o) = 11 a
nd 22 (w(o) = [H2O]/[CTAB]). The effect of w(o) on the reaction rate w
as investigated. A solid-phase strategy was developed for the synthesi
s of methyl-cytidyl-(3'-5')-5'-amino-5'-deoxythymidine. The nucleotide
coupling yielding the expected product occurred readily in reverse mi
celles. Nucleotide coupling is thus possible in reverse micelles, and
this is discussed in connection with the micellar self-replication pro
gram.