Jing-Chao Tao

Glycosylation of 6-amino-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine and its iodo- and bromo- analogues with the protected ribofuranose and 2′-deoxyribofuranose under different conditions resulted in the synthesis of N⁹- and N⁸-glycosylated purine nucleosides. Five key intermediate nucleosides, having 6-methoxy, 7-iodo, and 2-bromo groups, were further derivatized to 23 final 8-aza-7-deazapurine nucleoside derivatives. The structures of N⁹- and N⁸-glycosylated products were assigned based on UV and NMR spectra. HMBC analysis of 2D NMR spectra and X-ray crystallographic studies of the representative compounds unambiguously verified the connection of ribose ring to N⁹- or N⁸-position of the purine ring. The anticancer activity of these new compounds was evaluated.

Two series of novel acylthiosemicarbazide and oxadiazole fused‐isosteviol derivatives were synthesized based on the 19‐carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines (HCT‐116, HGC‐27, and JEKO‐1) using an MTT assay. Lead compounds from the acylthiosemicarbazides (4) showed IC₅₀ values in the lower micromolar range. For example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory activities against the three cell lines with IC₅₀ values of 0.95–3.36 μm. Furthermore, 2D‐HQSAR and 3D‐topomer CoMFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.

Chiral primary amine–squaramides have not been extensively studied to date in the field of organocatalysis. In this paper, novel chiral squaramides derived from natural product stevioside were developed. Both enantiomers of a series of γ-nitroaldehydes were generated by using these squaramide catalysts for the Michael addition reaction of isobutyraldehyde to nitroolefins. This asymmetric reaction proceeded well to afford the desired products in high yields (up to 98%) with high to excellent enantioselectivities (up to 99% ee).

A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3’-fluorinated analogues were constructed from a common 3’-deoxy-3’-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3’-fluororibose purine nucleosides1–15and eight 3’-fluororibose 2-chloro/2-aminopurine nucleosides16–23with various substituents at position 6 of the purine ring were efficiently synthesized. Furthermore, 3’-fluorine analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer) and 143B (osteosarcoma cancer) tumor cell lines. We have demonstrated 3’-fluorine purine nucleoside analogues display potent tumor cell growth inhibition activity at sub- or low micromolar concentration.

Copper-catalyzed asymmetric allylation of chiral N-tert-butanesulfinyl imines has been described. Dual stereocontrol, through the combination of a chiral auxiliary and a chiral copper complex, has played an important role in achieving the nearly perfect diastereoselectivities (all dr > 99 : 1), especially for ketimine substrates.

A simple and efficient one-pot approach for assembling novel spiro[indolepyranopyrrole] derivatives was developed and used to prepare a series of biologically important compounds. The reaction was easily performed with high efficiency under very simple and mild conditions without any catalysts and it gave good yields, avoiding time-consuming costly synthesis and laborious workup and purification of products. The cytotoxic activities of these new spiro[indolepyranopyrrole] derivatives were evaluated in vitro. Most of the tested compounds exhibited significant cytotoxicities to Raji cell lines.

A doubly stereocontrolled organocatalytic asymmetric Michael addition to the synthesis of substituted succinimides is described. Starting from aldehydes and maleimides, both enantiomers of the succinimides could be obtained in high to excellent yields (up to 98%) and enantioselectivities (up to 99%) when one of the two special chiral diterpene‐derived bifunctional thioureas was individually used as a catalyst. Moreover, these catalysts can be efficiently used in large‐scale catalytic synthesis with the same level of yield and enantioselectivity. Chirality 00:000–000, 2014.