The first attempts to synthesize oligo or poly(ribonucleotide)s (Table 7.1) were published shortly before 1960 (Khorana et al. 1956; Tener et al. 1958; Michelson 1959). A. M. Michelson polymerized the 2′,3′-cyclophosphates of all four nucleosides by means of phenyl phosphorochloridate (Scheme 7.1) and obtained mixtures of 2′,5′and 3′,5′connected nucleoside polyphosphates (Scheme 7.2a). This author also described a stepwise synthesis up to a DP of 6. Khorana and coworkers (Khorana et al. 1956, 1957; Tener et al. 1958; Coutsogeorgupopulos and Khorana 1964) used N,N′-dicyclohexylcarbodiimide as condensing agent and avoided the problem of reactions at the 2′-OH group by using thymidylic acid (a 2′-deoxynucleoside) as monomer (Scheme 7.3a). In a later publication (1964), they blocked the 2′-OH group by acetylation and used the 3′-phosphates as monomers for polycondensation (Scheme 7.3b). Oligo(nucleotide)s up to a DP of 6 were isolated, and oligo(nucleotide)s up to DP 11 were identified by chromatography.