Synthesis of a Tetracyclic G∧C Scaffold for the Assembly of Rosette Nanotubes with 1.7 nm Inner Diameter

Abstract

The synthesis of a tetracyclic self-complementary molecule 4 for self-assembly into rosette nanotubes is presented. This new heterocycle has a core structure containing two pyrido[2,3-d]pyrimidine molecules fused together and features the Watson Crick hydrogen bond donor acceptor arrays of both guanine (G) and cytosine (C). Current methods to synthesize pyrido[2,3-d]pyrimidines require harsh conditions and long reaction times and result usually in low product yields. This is particularly problematic for the direct incorporation of functional groups that cannot withstand these conditions. Here, we present an efficient approach to access the multifunctional pyrido[2,3-d]pyrimidine intermediate 2 under relatively mild conditions using three regioselective SNAr reactions at C2, C4, and C7 on the trichloro compound I. The electron-withdrawing group and amino functionalities on 2 are then used as a handle to install the third and fourth rings of 4 using a Friedkinder-type condensation followed by mixed urea synthesis and cyclization.