Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This str...

We developed neutral iridium catalysts with chiral spiro phosphine-carboxy ligands (SpiroCAP) for asymmetric hydrogenation of unsaturated carboxylic acids. Different from the cationic Crabtree-type catalysts, the iridium catalysts with chiral spiro phosphine-carboxy ligands are neutral and do not require the use of a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF-) counterion, which is ne...

A new cytochrome P450 monooxygenase, FcpC, from Streptomyces virginiae IBL-14 has been identified. This enzyme is found to be responsible for the bioconversion of a pyrano-spiro steroid (diosgenone) to a rare nuatigenin-type spiro steroid (isonuatigenone), which is a novel C-25-hydroxylated diosgenone derivative. A whole-cell P450 system was developed for the production of isonuatigenone via th...

The title compound, C(35)H(36)N(4)O(4), was prepared as a spiro-lactam ring formation of rhodamine B dye for comparison with a ring-opened form. The xanthene ring system is approximately planar. The r.m.s. deviation from planarity is 0.064 (6) Å for the xanthene ring. The dihedral angles formed by the spiro-lactam and 2,4-dihydroxy-benzene rings with the xanthene ring system are 86.6 (9) and 88...

The title compound, C(36)H(36)N(4)O(4), was prepared as a spiro-lactam ring formation of the rhodamine dye for comparison with a ring-opened form. The xanthene ring system is approximately planar [r.m.s. deviations from planarity = 0.023 (9) Å for the xanthene ring]. The dihedral angles formed by the spiro-lactam and 1,3-benzodioxole rings with the xanthene ring system are 86.8 (1) and 74.3 (1)...

The relaxant effect of the lactone of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g) with and without endothelium, precontracted with 1.0 microM phenylephrine. The lactone presented a greater potency than rosuvastatin in relaxing aortic rings. Unlike rosuvastatin, the effect of its lactone was endothelium-independent. Pretreatment with either indomethacin (10 micro...

Labeled 25-hydroxyvitamin D3-26,23-lactone was isolated from the serum of vitamin D-repleted rats given [3 alpha-3H]-25-hydroxyvitamin D324 hr prior to sacrifice. The metabolite was identified by cochromatography with the authentic lactone on straight-phase and reversed-phase high-performance liquid chromatography. Production of the lactone was abolished by nephrectomy indicating that the kidne...

A six-membered N-heterocyclic carbene fused with a spiro-scaffold is designed. The new NHC shows stronger σ-donation ability than typical 5-membered NHCs. This property leads to interesting reactivities of this spiro-fused six-membered NHC. For example, the NHC-BF3 Lewis pair complex can be readily prepared by using LiBF4 as the BF3 source, or through a direct bond-reconstruction of the tetrafl...

Inhibition of the MDM2-p53 protein-protein interaction is being actively pursued as a new anticancer therapeutic strategy, and spiro-oxindoles have been designed as a class of potent and efficacious small-molecule inhibitors of this interaction (MDM2 inhibitors). Our previous study showed that some of our first-generation spiro-oxindoles undergo a reversible ring-opening-cyclization reaction th...

objective during the last three decades sesquiterpenoid lactones have emerged as one of the largest groups of plant products with over 3000 naturally occurring substances known. the genus artemisia characteristically contains this biologically active type of secondary metabolites. with respect to increasing interest in the cytotoxic, antibiotic, phototoxic and antineoplastic activities of sesqu...