Acetyl hexapeptide-3, a competitive SNAP-25 inhibitor that mimics the action of botulinum neurotoxins but is nontoxic, was successively synthesized in a solution by peptide chemistry with a “3+2+1” fragment coupling strategy. The difficulties encountered in the convergent route, an optimization on scalable process, and controls on potential epimerization are systematically discussed. Final purification led to the target product’s overall 36.5% yield with 98.3% purity and excellent optical purity.

One step synthesis of the natural product indirubin by reductive coupling of isatin with KBH4 is described and a possible mechanism for the reaction is proposed. Eleven indirubin derivatives were obtained easily from the corresponding substituted isatin.Download high-res image (121KB)Download full-size image

Kilogram-scale synthesis of a bioactive pentapeptide in solution by “3 + 2” fragment coupling strategy has been successively accomplished in the development of OGP (10–14), a minimal OGP-derived sequence that retains the full proliferative activity of the osteogenic growth peptide. The synthetic scheme, coupling conditions, and scaling-up of the process are systematically studied; the epimerization of the tripeptide fragment and pentapeptide are also evaluated.

Tetrahydro-β-carbolines with strictosamide skeleton have been synthesized via intermolecular condensation, selective reduction, and intramolecular cyclization starting from phthalic anhydrides and tryptamine. The reactions are carried out under mild conditions with a wide range of substrates and functional groups.Starting from phthalic anhydride and tryptamine, the synthesis of tetrahydro-β-carbolines has been described via intermolecular condensation, selective reduction and intramolecular cyclization.

Biomimetic transformation of gentiopicroside was carried out by β-glucosidase at pH 7.0 for 3 days at 37 °C. Two products, erythrocentaurin and 5,6-dihydro-5-formyl-6-methyl-1H,3H-pyrano[3,4-c]pyran-1-one were isolated and identified by 1H NMR, 13C NMR, UV, IR, MS and elemental analyse. The possible mechanisms were discussed.