Jiaan Shao

One-pot three-component approach to the synthesis of polyfunctional pyrazoles.

A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed.

Palladium-Catalyzed C–H Functionalization Using Guanidine as a Directing Group: Ortho Arylation and Olefination of Arylguanidines

Palladium-catalyzed C-H functionalization using guanidine as the directing group was achieved under mild reaction conditions. Various guanidine derivatives were produced in moderate to good yields by using simple unactivated arenes or ethyl acrylate as the source of arylation or olefination, respectively.

A "one-pot" multicomponent approach to polysubstituted 4-aminopyridines.

A novel and facile domino reaction has been developed to synthesize a variety of polysubstituted 4-aminopyridines from α-azidovinylketones, aldehydes and methylamine derivatives in reasonably good yields under mild conditions. Additionally, a possible mechanism is proposed.

A traceless approach to amide and peptide construction from thioacids and dithiocarbamate-terminal amines

A novel and traceless strategy has been devised that allows a coupling of thioacids and dithiocarbamate-terminal amines. This strategy had been assumed to be dependent on the attachment of a functional equivalent of a cysteine side chain in earlier native chemical ligation approaches. This approach enables the traceless removal of CS2 to directly generate the desired amide bond and is compatible with a range of unprotected side chains of amino acid. The ability to produce amide or peptides by a traceless removal of the auxiliary is a significant virtue of the method. Meanwhile, the application of this new peptide-bond-forming reaction to the synthesis of novel endomorphin (EM) derivatives with various binding potencies was realized.

Tuning the Annulation Reactivity of Vinyl Azides and Carbazates: A Divergent Synthesis of Aza-pyrimidinones and Imidazoles

A divergent cascade annulation has been developed using readily available vinyl azides and carbazates with a wide range of substituents. Vinyl azides were successfully applied as bifunctional partners to prepare aza-pyrimidinones via 6-ring closure with carbazates as well as to construct polyfunctionalized imidazoles via 5-ring closure with N-substituted carbazates. The aza-heterocycles were obtained with high levels of chemoselectivity and excellent yields.

Synthesis of poly-functionalized imidazoles via vinyl azides annulation

An efficient annulation of vinyl azides with activated imines has been developed for the synthesis of poly-functionalized imidazole derivatives. This reaction includes thermal decomposition of vinyl azides to 2H-azirines, nucleophilic attack of 2H-azirines with activated imines and subsequent cyclization to desired imidazoles.

Highly efficient and eco-friendly protocol to functionalized imidazoles via ring-opening of α-nitro epoxides

A simple and direct synthesis of functionalized imidazoles from α-nitro-epoxides and amidines was developed. This reaction could proceed smoothly in a highly efficient and eco-friendly manner in moderate to excellent yields. A plausible mechanism has also been proposed.

Hepatic differentiation of rat mesenchymal stem cells by a small molecule.

Mesenchymal stem cells (MSCs) are capable of self‐renewal and multilineage differentiation. A periodic acid–Schiff (PAS) stain‐based assay was developed to screen for small‐molecule inducers of hepatic differentiation of bone marrow MSCs. 2‐(4‐Bromophenyl)‐N‐(4‐fluorophenyl)‐3‐propyl‐3H‐imidazo[4,5‐b]pyridin‐5‐amine (SJA710‐6) was identified as a novel small molecule able to induce the differentiation of rat MSCs (rMSCs) toward hepatocyte‐like cells in vitro, where rMSCs treated with SJA710‐6 have typical morphological and functional characteristics of hepatic cells, including glycogen storage, urea secretion, uptake of low density lipoprotein (LDL) and expression of hepatocyte‐specific genes and proteins. Expression of FoxH1 (FAST1/2) induces the differentiation of rMSCs towards hepatocyte‐like cells, suggesting that this gene plays an important role in the hepatic fate specification of rMSCs.

6-Oxooxazolidine-quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR.

Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFR(T790M) and EGFR(L858R) kinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants.

Base-mediated synthesis of highly functionalized 2-aminonicotinonitriles from α-keto vinyl azides and α,α-dicyanoalkenes

A novel access to highly functionalized 2-aminonicotinonitriles via efficient annulations of α-keto vinyl azides and α,α-dicyanoalkenes is described. This annulation was achieved via base-mediated ring-openings and intramolecular rearrangements. A possible mechanism is also proposed.