Conformationally Restrained Chiral Analogues of Spermine:  Chemical Synthesis and Improvements in DNA Triplex Stability

The synthesis of novel chiral analogues of spermine, 11 (2 R,4 S ) and 14 (2 S,4 R ), is reported starting from trans -4-hydroxy- l -proline 3 . These cyclic analogues are generated from linear, achiral spermine by incorporating a pyrrolidine ring on the backbone to effect conformational rigidity, with simultaneous creation of two asymmetric centers. The chiral analogues bind both AT and CG rich DNA duplexes as effectively as spermine and exhibit even better association with DNA triplex than spermine. The newer analogues have features for structural elaboration to novel molecular entities of potential importance in therapeutics and material design.