PNA SYNTHESIS USING A BASE LABELED AMINO PROTECTIVE GROUP

摘要

A process is claimed for preparing peptide nucleic acid (PNA) oligomers of formula (I). Ro=H, 1-18C alkanoyl, 2-19C alkoxycarbonyl, 3-8C cycloalkanoyl (sic), 7-15C aroyl, 3-13C heteroaroyl or a gp. which enhances the intracellular uptake of the oligomer or interacts with a target nucleic acid during hybridisation; A and Q=amino acid residues; k and m=0-20; B=a nucleotide base, opt. in prodrug form; Qo=OH, NH2 or NHR''; R''=1-18C alkyl, 2-18C aminoalkyl or 2-18C hydroxyalkyl; n=1-50. The process comprises: (a) opt. coupling amino acids (Q') to a support of formula L-(Polymer) by solid-phase synthesis to give (Q')m-L-(Polymer), where L=a linking gp. contg. Qo in latent form and Q'=Q with optional side-chain protection; (b) coupling a cpd. of formula (II) to L-(Polymer) or (Q')m-L-(Polymer), where PG=a base-labile protecting gp. and B'=a nucleotide base with a protected exocyclic amino gp.; (c) removing PG; (d) repeating steps (b) and (c) n-1 times; (e) opt. coupling amino acids (A') to the prod. by solid-phase synthesis, where A'=A with optional side-chain protection, and introducing Ro if Ro is other than H; and (f) cleaving the PNA oligomer from the prod. of formula (III) and simultaneously or subsequently deprotecting B', A' and Q'. Also claimed are cpds. (II) and a process for preparing them.