Total Synthesis of (-)-Vindorosine.

Outlined herein is a novel and scalable synthesis of (-)-vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone-derived lithium dienolates with indolyl N-tert-butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza-Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (-)-vindorosine and related alkaloids.

16-O-Methyl-cafestol.

THE TITLE COMPOUND [SYSTEMATIC NAME: (3bS,5aS,7R,8R,10aR,10bS)-7-meth-oxy-10b-methyl-3b,4,5,6,7,8,9,10,10a,10b,11,12-dodeca-hydro-5a,8-methano-5aH-cyclo-hepta-l[5,6]naph-tho[2,1-b]furan-7-methanol], C(21)H(30)O(3), was isolated from the beans of Coffea robusta. The mol-ecule contains five fused rings including a furan ring. The two six-membered rings are in chair conformations, but the third six-membered ring and the five-membered aliphatic ring adopt envelope conformations. Inter-molecular O-H⋯O hydrogen bonding is present in the crystal structure.

Highly Oxygenated Grayanane Diterpenoids from Flowers of Pieris japonica and Structure-Activity Relationships of Antifeedant Activity against Pieris brassicae.

Six new highly oxygenated grayanane diterpenoids, neopierisoids G-L, 1-6, together with 10 known related compounds, 7-16, were identified from the flowers of the poisonous plant Pieris japonica. The structures were elucidated on the basis of comprehensive NMR spectroscopy and mass analysis. The relative configurations of 1-6 were elucidated by analysis of ROESY spectra and comparison of NMR data with the analogues. The absolute configurations of 1-6 were established by the X-ray diffraction analysis of 1 and comparison of the CD spectra of 1-6. Compared with the skeleton of the normal grayanane diterpenoids, compounds 1-6 shared an unusual seco A ring moiety. The antifeedant activities of compounds 1-16 against Pieris brassicae were evaluated by using a dual-choice bioassay, and compounds 1-10 with a normal grayanane skeleton showed potent antifeedant activity against P. brassicae. The structure-activity relationships of antifeedant activities of 1-16 against P. brassicae are discussed.

Synthesis, characterization and in vitro evaluation of a series of novel polyrotaxane-based delivery system for artesunate.

A series of novel artesunate-polyrotaxanes (ATS-PRs) with folic acid capped, in which artesunate (ATS) was covalently bound to a cyclodextrin (CD) of the polyrotaxane (PR), were synthesized and were characterized by NMR, XRD, TG and DSC. The cytotoxicities of ATS-PRs on human colon cancer cell lines HT-29, SW480, HTC116 and DLD-1 showed that their antitumor activities were better than that of artesunate (ATS) and dihydroartemisinin (DHA). These ATS-PRs may provide a useful approach to the development of a highly effective drug candidate for the chemotherapy of human colon cancer.

Synthesis, characterization, and in vitro evaluation of artesunate-ß-cyclodextrin conjugates as novel anti-cancer prodrugs.

A novel series of artesunate-ß-cyclodextrin (ATS-ß-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of ß-cyclodextrin (ß-CD) through amino bond formation, were synthesized and characterized by (1)H NMR, HRMS, 2D NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-ß-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-ß-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NßCD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC50 values of 0.58, 1.62, and 5.18µmol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin.

Scutellarin-cyclodextrin conjugates: synthesis, characterization and anticancer activity.

A series of scutellarin-cyclodextrin conjugates (SCU-CD conjugates), in which scutellarin was covalently bound to one of the primary hydroxyl groups of ß-CD, were prepared, and their structures were determined using NMR and MS. These conjugates were further characterized by XRD and TG. The results showed that the aqueous solubility of the conjugates was much higher than that of scutellarin, and the conjugates could hardly be hydrolyzed to scutellarin in aqueous solutions. The cytotoxicity of SCU-CD conjugates on human colon cancer cell lines HT-29, SW480, Lovo and HTC116 indicated that the antitumor activities of the conjugates were better than that of scutellarin. This high antitumor activity, along with the satisfactory aqueous solubility and high stability of the conjugates, will be potentially useful for their application on human colon cancer chemotherapies.

A novel polyrotaxane-based delivery system for scutellarin: preparation, characterization, and in vitro evaluation.

The safe and effective polyrotaxane-based drug delivery system could potentially increase the antiproliferative activity of antitumor medicine. A novel scutellarin-polyrotaxane (SCU-PR), in which scutellarin (SCU) was covalently bound to one of the hydroxyl groups of polyrotaxane (PR), was synthesized, and its characterization was further investigated by NMR, XRD, TG, DSC. The cytotoxicity of SCU-PR was assessed in vitro using human HCT116 and LOVO cell lines in results that the IC50 values of SCU-PR (1.03×10(-6) and 1.01×10(-6)mol/L, respectively), which compared with those of free SCU (7.80×10(-5) and 7.70×10(-5)mol/L, respectively), were lower. The valuable properties of SCU-PR will be potentially useful for its application on human colon cancer chemotherapies.