No abstract

A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.

No abstract

A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the causative toxins for ciguatera fish poisoning, has been developed. The synthesis features convergent coupling to form dioxane acetal, regioselective acetal cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate followed by intramolecular radical cyclization to construct the oxepane ring G, and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1 equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one predominating. This is the first illustration that reproduces the preference for the UP conformer over the DOWN one, which preference was observed for natural ciguatoxins.