Oxidative Free-Radical C(sp2)-H Bond Chlorination of Enaminones with LiCl: Access to Highly Functionalized α-Chlorinated Enaminones.

An oxidative free-radical C(sp2)-H bond chlorination strategy of enaminones has been developed by using LiCl as a chlorinating reagent and K2S2O8 as an oxidant. This transformation provides a new and straightforward synthetic methodology to afford highly functionalized α-chlorinated enaminones with a Z-configuration in good to excellent yields.

Divergent Synthesis of 2-Chromonyl-3-hydrazono-chromones and 2-Alkoxy-3-hydrazono-chromones through Switchable Annulation Reactions of o-Hydroxyphenylenaminones with Aryldiazonium Salts.

An unprecedented selective chromone annulation reaction controlled by solvent for the divergent synthesis of two types of 2,3-disubstituted chromone skeletons has been developed. A variety of 2-chromonyl-3-hydrazono-chromones and 2-alkoxy-3-hydrazono-chromones were constructed efficiently from readily available o-hydroxyphenylenaminones (o-HPEs) and aryldiazonium salts at room temperature. This strategy is highly chemoselective and features mild reaction conditions, broad substrate scope, broad functional group tolerance, easy gram-scale preparation, and simple filtration to obtain the pure products without tedious column chromatography.

Switchable Skeletal Rearrangement of Hexahydro-4H-indol-4-ones: Divergent Synthesis of Dihydroxy-4H-cyclopenta[b]pyridin-4-ones and 8-Alkenyl Oxepane-2,6-diones.

An unprecedented base-controlled selective skeletal rearrangement reaction of hexahydro-4H-indol-4-ones has been developed. In this protocol, highly functionalized dihydroxy-4H-cyclopenta[b]pyridin-4-ones and 8-alkenyl oxepane-2,6-diones were prepared with a broad substrate scope and high chemoselectivity in moderate to excellent yields selectively by modulating LiOH and Et3N. In addition, the newly formed 8-alkenyl oxepane-2,6-dione scaffolds could be easily further derivatized to 5-(pyrrol-2-yl)dihydrofuran-2(3H)-ones through a rare intramolecular rearrangement reaction.

Rh(III)-catalyzed selective mono- and dual-functionalization/cyclization of 1-aryl-5-aminopyrazoles with iodonium ylides.

An efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as a single coupling partner was demonstrated, in which fused benzodiazepine skeletons were obtained in excellent yields. This method greatly improved an effective approach to dual C-H unsymmetrical functionalization.

DNA shuffling of uricase gene leads to a more "human like" chimeric uricase with increased uricolytic activity.

Urate oxidase (Uox) is the enzyme involved in purine metabolism. Pseudogenization of Uox gene is the underlying mechanism of hyperuricemia and gout in human. Although Uox from various microorganisms has been used in clinical practice for many years, its application is limited by potential immunogenicity. In order to develop a more "human like" uricase, DNA shuffling was used to create chimeric uricase with both improved enzymatic activity and increased homology with deduced human uricase (dHU) gene. By using wild porcine uricase (wPU) gene and dhu as parental genes, a diverse chimeric library was generated. After preliminary screening by a "homebrew" high throughput protocol, approximately 100 chimeras with relatively high enzymatic activity were obtained. By further activity comparison of the purified enzymes, chimera-62 with increase in both activity and homology with dHU compared with wPU was selected. Its Km and catalytic efficiency were determined as 9.43±0.04µM and 2.67s(-1)µM(-1) respectively. There were 33 amino acid substitutions in chimera-62 when compared with dHU and 5 substitutions when compared with wPU. By homology modeling and 3-D structure analysis, it was speculated that mutations G248S and L266F contributed to the increased activity of chimera-62 by increasing the stability of α-helix and surface polarity respectively.