Short Total Synthesis of (−)-Kainic Acid

A short total synthesis of (−)-kainic acid has been developed involving a novel diastereofacial differentiating Cu-catalyzed Michael addition–cyclization reaction, which provided access to a chiral pyrroline in a highly stereoselective manner. The chiral pyrroline was converted to (−)-kainic acid via the stereoselective 1,4-reduction of the pyrroline double bond in three steps

Structure Determination of a New Juvenile Hormone from a Heteropteran Insect

The structure of the juvenile hormone (JH) in the suborder Heteroptera, order Hemiptera, has been known for a very long time to be different from the JH of other orders, but the structure has been a matter of controversy. The structure was first elucidated by an unprecedented approach involving the screening of a JH molecular library. The novel Heteroptera-specific JH (JHSB₃) is a new category of JH that is featured by the skipped bisepoxide structure

The Structure of (−)-Kaitocephalin Bound to the Ligand Binding Domain of the (S)-α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)/Glutamate Receptor, GluA2

Background: The natural product (−)-kaitocephalin is a potential scaffold for development of subtype-specific glutamate receptor antagonists. Results: The crystal structure of (−)-kaitocephalin bound to an AMPA receptor ligand binding domain was determined. Conclusion: The orientation of (−)-kaitocephalin in the binding site can explain the subtype selectivity of the parent compound. Significance: Comparisons with the structure of other glutamate receptors provides avenues for development of new subtype-specific antagonists. Glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and excessive stimulation of these receptors is involved in a variety of neurological disorders and neuronal damage from stroke. The development of new subtype-specific antagonists would be of considerable therapeutic interest. Natural products can provide important new lead compounds for drug discovery. The only natural product known to inhibit glutamate receptors competitively is (−)-kaitocephalin, which was isolated from the fungus Eupenicillium shearii and found to protect CNS neurons from excitotoxicity. Previous work has shown that it is a potent antagonist of some subtypes of glutamate receptors (AMPA and NMDA, but not kainate). The structure of kaitocephalin bound to the ligand binding domain of the AMPA receptor subtype, GluA2, is reported here. The structure suggests how kaitocephalin can be used as a scaffold to develop more selective and high affinity antagonists for glutamate receptors

Regioselective Prins Cyclization of Allenylsilanes. Stereoselective Formation of Multisubstituted Heterocyclic Compounds

The Prins cyclization of hydroxy or amino group-containing allenylsilanes with carbonyl compounds occurred at the allenic terminus in a regio- and stereoselective manner to give the di- or trisubstituted tetrahydrofurans, tetrahydropyrans, and pyrrolidines. During the reaction, the allenic axial chirality of the starting material was efficiently transferred to the newly formed carbon chiral centers of the product