Synthesis and DNA‐Binding Studies of A New Cyclic Dimeric Symmetrical Pseudo‐Turn Mimetic

Abstract

A new dimeric cyclic 24 member symmetrical turn analogue was synthesized efficiently by an intramolecular Heck reaction. This facile reaction has produced selectively a single dimeric product having two sets of intramolecular hydrogen bonds (IHB) at the two ends of it. Different experimental studies have unambiguously proved the presence of a pseudo‐turn like structure. Furthermore, it was shown that this molecule binds to the minor groove of DNA just like a known minor groove binder, DAPI (4′,6‐diamidino‐2‐phenylindole).

Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs

“…Since NMR spectroscopy detected the presence of hydrogen bonds (marked as dashed lines in Figure 2A) in both the linear precursor and its corresponding product, conformational preorganization through such intramolecular hydrogen bonding was believed to promote cyclization. More recently, Banerji et al synthesized symmetrical pseudo-turn mimics 12 via double Heck cross-coupling (Figure 2B) [29]. Initially intending to build 12-membered rings, they were unable to obtain any monomeric cyclization product, even under high dilution More recently, Banerji et al synthesized symmetrical pseudo-turn mimics 12 via double Heck cross-coupling (Figure 2B) [29].…”

“…More recently, Banerji et al synthesized symmetrical pseudo-turn mimics 12 via double Heck cross-coupling (Figure 2B) [29]. Initially intending to build 12-membered rings, they were unable to obtain any monomeric cyclization product, even under high dilution More recently, Banerji et al synthesized symmetrical pseudo-turn mimics 12 via double Heck cross-coupling (Figure 2B) [29]. Initially intending to build 12-membered rings, they were unable to obtain any monomeric cyclization product, even under high dilution conditions; rather, dimeric 24-membered macrocycles were produced in 40-45% yields with exclusive E-geometry at the newly formed alkenes.…”