Erythrina Alkaloid Analogues as nAChR Antagonists-A Flexible Platform for Leads in Drug Discovery.

Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at ß2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and (+)-Cocculidine, both found to be potent antagonists of the ß2-containing nAChRs.

Enantioselective Total Synthesis of (+)-Dihydro-ß-erythroidine.

Erythrina alkaloids represent a rich source of complex polycyclic, bioactive natural products. In addition to their sedative and hypotensive effect, their curare-like activity and structural framework have made them attractive targets for synthetic and medicinal chemists. (+)-Dihydro-ß-erythroidine (DHßE), the most potent nicotine acetylcholine receptor antagonist (nAChR) of the Erythrina family, is synthesized for the first time in 13 steps from commercially available material.

Polycyclic alkaloids via transannular Mannich reactions.

The tricyclic compound , representing the framework of the cylindricine and lepadiformine alkaloids, was prepared in a single operation via the first example of a transannular Mannich reaction involving a macrocyclic diketoamine .

Efficient and highly enantioselective formation of the all-carbon quaternary stereocentre of lyngbyatoxin A.

Indole 25, an advanced intermediate in a projected enantioselective total synthesis of lyngbyatoxin A 1, was prepared from allylic alcohol 11 in 9 steps and >95% ee, key transformations being the enantiospecific rearrangement of vinyl epoxide 14 and the Hemetsberger-Knittel reaction of azide 24.

A C2-symmetric nickel diamine complex as an asymmetric catalyst for enecarbamate additions to butane-2,3-dione.

Butane-2,3-dione was activated towards nucleophilic addition of enecarbamates by a series of metal triflate complexes of a C2-symmetric diamine to give stereogenic, aldol-like, t-alcohols, a novel nickel(II) triflate complex was identified as a good catalyst for this asymmetric transformation, and an aquo nickel(II) complex was identified by XRD techniques.