Enantioselective total synthesis of (-)-limaspermidine and formal synthesis of (-)-1-acetylaspidoalbidine.

Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors.

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).

Enantioselective and regioselective organocatalytic conjugate addition of malonates to nitroenynes.

The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has been developed. The 1,4-addition adducts were obtained solely, in moderate to good yields (up to 93%) with good enantioselectivities (up to 99% ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral β-alkynyl acid derivatives and synthetically useful chiral nitroalkynes.

Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke.

Background: High-resolution MRI has been shown to be capable of distinguishing intact, thick fibrous caps from thin and ruptured caps in human carotid atherosclerosis in vivo. The aim of this study was to determine whether MRI identification of fibrous cap thinning or rupture is associated with a history of recent transient ischemic attack (TIA) or stroke.

Methods And Results: Fifty-three consecutive patients (mean age, 71 years; 49 male) scheduled for carotid endarterectomy were recruited after obtaining informed consent.