Conformationally-preorganized, miniPEG-containing γ-peptide nucleic acids

摘要

The present invention relates to γ-PNA monomers according to Formula I where substituent groups R1, R2, R3, R4, R5, R6, B and P are defined as set forth in the specification. The invention also provides methodology for synthesizing compounds according to Formula I and methodology for synthesizing PNA oligomers that incorporate one or more Formula I monomers.

主权项

1. A method for preparing a compound according to Formula I, comprising: (i) contacting the compound of Formula II with a compound according to Formula III to obtain a compound according to Formula IV (ii) contacting a compound according to Formula V with a coupling agent; and (iii) adding the product of step (ii) to the compound according to Formula IV to obtain the compound of Formula I, wherein B is a nucleic acid base selected from adenine, guanine, cytosine, thymine or uracil; Y is selected from the group consisting of bromine, iodine, 4-toluenesulfonate and methanesulfonate; R1, R2 and R5 each independently are selected from the group consisting of H, linear or branched (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)hydroxylalkyl, (C3-C8)aryl, (C3-C8)cycloalkyl, (C3-C8)aryl(C1-C6)alkylene, (C3-C8)cycloalkyl(C1-C6)alkylene, −CH2(OCH2CH2)qOP1, −CH2—(OCH2—CH2)q—NHP1, —CH2—(OCH2—CH2)q—SP1, and —CH2—(SCH2—CH2S)q—SP1; R3 and R4 each independently are H; R6 is selected from the group consisting of H, linear or branched (C1-C8)alkyl, substituted or unsubstituted (C3-C8)aryl and (C3-C8)aryl(C1-C6)alkylene; P is selected from the group consisting of H, 9-fluorenylmethyloxy carbonyl, Boc, benzyloxycarbonyl, tosylate, benzyl, alloc, trityl, benzhydryloxycarbonyl (Bhoc), O-nitroveratryloxycarbonyl (Nvoc), 1-(4,4-dimethyl-2,6-dioxacyclohexylidene)ethyl (Dde), diathiasuccinoyl (Dts), benzothiazole-2-sulfonyl (Bts), dimethoxytrityl and monomethoxytrityl; P1 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)aryl, (C3-C8)cycloalkyl, (C3-C8)aryl(C1-C6)alkylene and (C3-C8)cycloalkyl(C1-C6)alkylene; and n and q are independently integers between 1 and 10 inclusive.