Cyclobutyl-carbonyl substituted PNA: synthesis and study of a novel PNA derivative

A new, optically active, cyclobutyl-carbonyl substituted PNA monomer has been synthesized stereoselectively from a chiral amino acid prepared from (+)-α-pinene. A conformational search shows a lack of conformational bias for the monomer and incorporation of the monomer into a standard oligomer is tolerated without changing the binding affinity towards sequence complementary RNA, DNA or PNA targets.

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Methyl (1′R,2R,3′S)-2-benzyloxycarbonylamino-4-(3′-acetyl-2′,2′-dimethylcyclobutyl)butanoateC21H29NO5[α]D = +20.2 (c 1.4, MeOH)Source of chirality: (+)-α-pinene and asymmetric hydrogenationAbsolute configuration: (1′R,2R,3′S)

Methyl (1′R,2R,3′S)-2-[2″-tert-butoxycarbonylamino-1″-[(thymin-1-yl)acetyl]aminoethyl]-4-(3′-acetyl-2′,2′-dimethylcyclobutyl)butanoateC27H42N4O8[α]D = +33.0 (c 1.0, MeOH)Source of chirality: (+)-α-pinene and asymmetric hydrogenationAbsolute configuration: (1′R,2R,3′S)

(1′R,2R,3′S)-2-[2″-tert-Butoxycarbonylamino-1″-[(thymin-1-yl)acetyl]aminoethyl]-4-(3′-acetyl-2′,2′-dimethylcyclobutyl)butanoic acidC26H39N4O8[α]D = +14.5 (c 1.1, MeOH)Source of chirality: (+)-α-pinene and asymmetric hydrogenationAbsolute configuration: (1′R,2R,3′S)