Patent ID: 6121418
Filing Date: 2000-09-19
Classification: C07D,C07K,C08G,Y02P

Abstract:
A process for preparing PNA oligomers of formula I ##STR15## in which R.degree. is hydrogen, C.sub.1 -C.sub.18 -alkanoyl, C.sub.1 -C.sub.18 -alkoxycarbonyl, C.sub.3 -C.sub.8 -cycloalkanoyl, C.sub.7 -C.sub.15 -aroyl, C.sub.3 -C.sub.13 -heteroaroyl, or a group which favors intracellular uptake of the oligomer;A is an amino acid residue;k is an integer from zero to 10;Q is an amino acid residue;m is an integer from 0 to 20;B is a nucleotide base which is customary in nucleotide chemistry,or a prodrug form thereof;Q.degree. is hydroxyl, NH.sub.2 or NHR"", with R"" is C.sub.1 -C.sub.18 -alkyl, C.sub.2 -C.sub.18 -aminoalkyl or C.sub.2 -C.sub.18 -hydroxyalkyl; andn is an integer of 1-50;comprising(a) coupling Q' using a method which is customary for solid phase synthesis, to a polymeric support of formula IIL-{polymer} (II)to result in a compound of formula (III)(Q').sub.m -L-{polymer} (III),whereinQ' is an amino acid Q, the side chain of which is optionally protected,m is an integer from 0 to 20, andL is an anchor group which contains radical Q.degree. in protected form;b) either coupling a compound of formula IV ##STR16## to a compound of formula III using coupling reagents conventionally employed in peptide chemistry,whereinPG is a base-labile amino protecting group, andB' is a nucleotide base which is protected on the exocyclic amino function; or, if m=0, coupling a compound of the formula IV directly to the polymeric support of the formula II using coupling reagents conventionally employed in peptide chemistry,(c) removing said protecting group PG using a suitable reagent;(d) repeating (b) and (c) n-1 times;(e) coupling A' sequentially k times using a method which is customary for solid phase synthesis, followed by coupling of R.degree., if R.degree. is not hydrogen, to produce a compound of formula Ia ##STR17## wherein A' is an amino acid A, the side chain of which is optionally protected; andR.degree., L, B', Q', k, m and n are as defined above;(f) cleaving the compound of formula I out of the compound of formula Ia using a weak or medium strength acid, whereby the protecting groups, if any, present on A', Q', or B' are removed simultaneously with or subsequent to said cleaving.