Chemical synthesis of the EPF-family of plant cysteine-rich proteins and late-stage dye attachment by chemoselective amide-forming ligations.

Chemical protein synthesis can provide well-defined modified proteins. Herein, we report the chemical synthesis of plant-derived cysteine-rich secretory proteins and late-stage derivatization of the synthetic proteins. The syntheses were achieved with distinct chemoselective amide bond forming reactions - EPF2 by native chemical ligation (NCL), epidermal patterning factor (EPF) 1 by the α-ketoacid-hydroxylamine (KAHA) ligation, and fluorescent functionalization of their folded variants by potassium acyltrifluoroborate (KAT) ligation.

Diastereoselective Construction of Tetrahydro-Dispiro[indolinone-3,2'-pyran-5',4″-pyrazolone] Scaffolds via an Oxa-Michael Cascade [4 + 2] Annulation Reaction.

A straightforward metal-free oxa-Michael cascade [4 + 2] annulation reaction was established between isatin-derived Morita-Baylis-Hillman (Is-MBH) alcohols with alkylidene pyrazolones to access structural diverse tetrahydro-dispiro[indolinone-3,2'-pyran-5',4″-pyrazolone] scaffolds bearing two tertiary and two quaternary stereocenters. The Is-MBH alcohol was utilized as an oxa-Michael donor for the first time as a new approach in highly atom-economical transformations. This method offered a wide range of bioinspired novel tetrahydro-dispirooxindole-pyran-pyrazolone derivatives in excellent yields (up to 96%) and diastereoselectivities (up to >20:1) in a shorter reaction time (15 min).

DHQZ-17, a potent inhibitor of the transcription factor HNF4A, suppresses tumorigenicity of head and neck squamous cell carcinoma in vivo.

A series of 2, 3-dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound (17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non-toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC of 1.

Diastereo- and Enantioselective Synthesis of 2,2-Disubstituted Benzofuran-3-one Bearing Adjacent Quaternary and Tertiary Stereocenters.

The first highly diastereo- and enantioselective synthesis of armeniaspirol analogues was achieved using L-proline derived bifunctional squaramide which outperformed commonly used organocatalysts. Excellent yield (up to 99%) with diastereoselectivity (up to 99:1) and enantioselectivity (up to 99%) were obtained for a wide range of substrates.

Enantioselective Synthesis of Dihydrospiro[indoline-3,4'-pyrano[2,3-c]pyrazole] Derivatives via Michael/Hemiketalization Reaction.

A new bifunctional squaramide organocatalyst derived from L-proline mediated the first enantioselective synthesis of dihydrospiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives in excellent enantioselectivity by reacting pyrazolones with isatylidine β,γ-unsaturated α-ketoester. This new catalyst outperformed widely used thioureas and squaramides in inducing enantioselectivity.

Palladium catalyzed asymmetric allylation of 3-OBoc-oxindoles: an efficient synthesis of 3-allyl-3-hydroxyoxindoles.

3-Allyl-3-hydroxyoxindoles were synthesized in very good enantio- (up to 97% ee) and diastereoselectivities (dr up to 7.6:1) with contiguous quaternary and tertiary stereogenic centers by employing tartrate derived bi(oxazoline) in Pd-catalyzed allylation of 3-OBoc-oxindole. Synthetic utility of 3-allyl-3-hydroxyoxindole was demonstrated by synthesizing a highly substituted spiro(oxindole-3,2'-tetrahydrofuran) derivative in good yield and stereoselectivity.