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A flexible strategy has been developed to synthesize divergent flavonoids bearing a chiral A-ring. As two key steps, the coupling via a boron-mediated aldol condensation and the cyclization via a highly stereoselective intramolecular Michael addition of 1,3-diketone proceed under mild conditions; thus, the chiral flavonoids bearing C-7 oxy functional groups or olefinic bonds are both easily accessible. Using this approach, the first synthesis of (+)-cryptogione F, (+)-cryptocaryanone B, and (+)-cryptochinones A and C, as well as stereoselective synthesis of (+)-cryptocaryone and (+)-cryptocaryanone A, were achieved from 2-deoxy-d-ribose in high overall yields.

The first total synthesis of zalypsis and the practical synthesis of phthalascidin (Pt-650) are achieved through the Pictet-Spengler cyclization coupling strategy. The direct iodination of the primary alcohol in trihydroxyl intermediate 26 followed by SN2 reaction with potassium phthalimide is employed to rapidly introduce the required amino functionality at C-22 on the pentacyclic framework. By the approaches, the two antitumor agents can be obtained from sesamol or N-Cbz- l -tyrosine with ca. 8%-10% overall yield.

The first synthesis of (+)-botryolide-E and its C-7 epimer has been achieved in 8 steps from d -Glucono-δ-lactone, and their antibiotic activities were also investigated preliminarily.

A concise formal synthesis of ecteinascidin 743 is described. Key features involve the coupling of the multisubstituted tetrahydroisoquinoline and phenylalaninol moieties via a regio- and stereoselective Pictet-Spengler cyclization as well as the subsequent chemoselective MOM protection of the phenol group, which opens a rapid access to the desirable pentacycle. The synthesis successfully delivered the advanced intermediate with the characteristic macrolactone from sesamol in 23 steps.

A practical strategy for the synthesis of both (–)- and (+)-concentricolide from salicylic acid has been developed. The key feature of the approach is sequential aromatic lithiation and condensation with an aldehyde directed by a chiral oxazoline unit derived either from L- or D-phenylalaninol, which is employed as an auxiliary.

A new short approach to (−)-lepadins A–C has been developed based on a stereocontrolled Diels–Alder reaction employing a chiral dienophile. With this approach, (−)-lepadin B is synthesized from 5-deoxy-d-ribose in 13 steps with 14.8% overall yield. The cis-decahydroquinoline core containing five stereocenters could be rapidly constructed via stereoselective cycloaddition and subsequent five-step one-pot hydrogenation–cyclization.

A useful and flexible strategy for synthesis of (-)- and (+)-infectocaryone from commercial sugars is developed. The key step of the synthesis is a new-type Diels-Alder reaction with good chemoselectivity and stereoselectivity, in which a mixture of alkene regioisomers in a dynamic equilibrium is employed as chiral dienophiles for the first time.

Porcine gamma interferon is a cytokine produced by activated T cells and NK cells with broad-spectrum antiviral activity and immunomodulatory function. However, pIFN-γ is a secretory protein that has a short half-life in organisms and is easily inactivated, making it difficult to apply widely in clinics. Therefore, we tried to optimize the expression of pIFN-γ in Pichia pastoris to obtain a large amount of highly active, easily purified pIFN-γ protein in vitro. Through C-terminal sequence analysis, we found a signal sequence (EKREAEAE) that was easily enzymolysed by a signal peptide enzyme, resulting in degradation and inactivation of the pIFN-γ protein. In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. Our data also showed that the fermentation process could significantly improve productivity. A recombinant Pichia pastoris strain with the optimized pIFN-γ gene could obtain a high yield of pIFN-γ protein, up to 9536 mg/L, after staged incubation for 0-24 h at 28°C, pH 6.0, and 50% dissolved oxygen (DO), followed by incubation for 24-72 h at 25°C, pH 6.0 and 30% DO. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry.

(−)-Renieramycin T, an interesting tetrahydroisoquinolinequinone alkaloid with a novel renieramycin–ecteinascidin mixed framework, is synthesized from the known phenol 16 in 22 steps with 6.2% overall yield. In the convergent route, the key cyclocondensation between the isoquinoline moiety 27 and trisubstituted phenylalaninol 14 is achieved with good selectivity to furnish bistetrahydroisoquinoline 29, which permits a rapid construction of the pentacyclic framework having a fully substituted aromatic A ring.