An attempted approach to the tricyclic core of haliclonin A: Structural elucidation of the final product by 2D NMR

We describe the design and execution of a novel synthetic route to the tricyclic core of haliclonin A, a tetracyclic marine natural product. The approach features Bachi's thiol-medicated free radical cyclization of alkenyl isocyanide to build the bridged ring system, and ring-closing metathesis (RCM) reaction to form the macrocycle. Execution of the synthetic plan ultimately resulted in a diazatricyclic compound. By means of 2D NMR techniques, the structure of this compound was revealed to an unexpected product 8. Analysis of the synthetic pathways allowed concluding that the unexpected product is a result of an unexpected migration of olefinic bond during dioxolanation of the 2-cyclohexenone derivative 7. This investigation also resulted in a concise construction of the functionalized hexahydro-1H-isoindole-1,5 (4H)-dione 12 and the macrocyclic tricyclic ring system 8. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.