Total Syntheses of (+)-α-Allokainic Acid and (-)-2- epi-α-Allokainic Acid Employing Ketopinic Amide as a Chiral Auxiliary.

Asymmetric Michael reaction of iminoglycinate 4 to α,ß-unsaturated esters had been developed with >98:<2 diastereoselectivity. A reverse of diastereoselectivity for Michael reaction could be achieved by the replacement of lithium enolate with magnesium enolate. This methodology was applied to the total syntheses of (+)-α-allokainic acid 1 and (-)-2- epi-α-allokainic acid 6 each in 11 synthetic steps starting from 4 in 17.8 and 18.0% yields, respectively.

S- Cis Diene Conformation: A New Bathochromic Shift Strategy for Near-Infrared Fluorescence Switchable Dye and the Imaging Applications.

In this paper, we present a novel charge-free fluorescence-switchable near-infrared (IR) dye based on merocyanine for target specific imaging. In contrast to the typical bathochromic shift approach by extending π-conjugation, the bathochromic shift of our merocyanine dye to the near-IR region is due to an unusual S- cis diene conformer. This is the first example where a fluorescent dye adopts the stable S- cis conformation. In addition to the novel bathochromic shift mechanism, the dye exhibits fluorescence-switchable properties in response to polarity and viscosity. By incorporating a protein-specific ligand to the dye, the probes (for SNAP-tag and hCAII proteins) exhibited dramatic fluorescence increase (up to 300-fold) upon binding with its target protein. The large fluorescence enhancement, near-IR absorption/emission, and charge-free scaffold enabled no-wash and site-specific imaging of target proteins in living cells and in vivo with minimum background fluorescence. We believe that our unconventional approach for a near-IR dye with the S- cis diene conformation can lead to new strategies for the design of near-IR dyes.