The research proposal outlines a plan for development and synthetic application of a modification of C-H insertion that was recently discovered in our labs. The noteworthy feature of C-H insertion is the ease of creation of quaternary chiral centers - structural element that is present in a number of bioactive natural compounds. Based on this methodology three total syntheses are proposed. The first project describes the synthesis of Bakuchinol (antioxidant, hepatoprotective, antibiotic compounds, with recently discovered PTP1B inhibitory activity in dose dependent manner with IC50 ca. 20 ?M). Also proposed is the synthesis of Rhazinilam, an anti-cancer compound that both induces spiralization of microtubules (IC50 ca. 7 ?M), and disassembly of microtubules (IC50 ca. 3 ?M). And finally, a synthetic approach to antibiotic Guanacastepene A (inhibitor of drug resistant strains of Staphylococcus aureus and Enterococcus faecalis) is described.
The project describes the development of C-H insertion on sulfonyl substrates as a synthetic method for creation of quaternary chiral centers, and its application to the synthesis of bioactive natural products: Bakuchinol, anti-tumor compound Rhazilinam, and antibiotic Guanacastepene. ? ? ?
| Liyanage, Duminda S; Jungong, Christian S; Novikov, Alexei V (2015) Oxidative conversion of ?-sultones to ?-lactones. Tetrahedron Lett 56:2269-2271 |
| Liyanage, Duminda S; Jungong, Christian S; Novikov, Alexei V (2015) SYNTHETICALLY USEFUL INTERMEDIATES BY DIAZOSULFONE AND SULFONATE C-H INSERTION. Synth Commun 45:226-231 |
| Jungong, Christian S; Novikov, Alexei V (2012) PRACTICAL PREPARATION OF RESVERATROL 3-O-?-D-GLUCURONIDE. Synth Commun 42:3589-3597 |
| Natori, Yoshihiro; Tsutsui, Hideyuki; Sato, Naoki et al. (2009) Asymmetric synthesis of neolignans (-)-epi-conocarpan and (+)-conocarpan via Rh(II)-catalyzed C-H insertion process and revision of the absolute configuration of (-)-epi-conocarpan. J Org Chem 74:4418-21 |
| Jungong, Christian S; John, Jinu P; Novikov, Alexei V (2009) Formation of six- vs. five-membered cyclic sulfones by C-H insertion. Tetrahedron Lett 50:1954-1957 |
| John, Jinu P; Jost, Joshua; Novikov, Alexei V (2009) Synthesis of plakortethers F and G. J Org Chem 74:6083-91 |
| Bequette, Joseph P; Jungong, Christian S; Novikov, Alexei V (2009) Enantioselective synthesis of Bakuchiol using diazosulfonate C-H insertion to install the quaternary center. Tetrahedron Lett 50:6963-6964 |
