Robert A. Holton

Selective protection of the C(7) and C(10) hydroxyl groups in 10-deacetyl baccatin III

Abstract New protocols for the selective protection of the C(7) and C(10) hydroxyl groups of 10-deacetyl baccatin III are described, leading to more efficient semisyntheses of taxol and taxol analogs. The C(10) hydroxyl group of 10-DAB can be highly selectively acylater or silylated, and subsequent selective protection of the C(7) hydroxyl group then becomes straightforward.

A novel asymmetric synthesis of cis-3-hydroxy-4-aryl azetidin-2-ones

Abstract Optically pure 3-keto-4-aryl azetidin-2-ones were prepared in high yield via the Staudinger reaction of an oxazolidone substituted ketene. Subsequent reduction with sodium borohydride quantitatively provided chiral cis -3-hydroxy-4-aryl azetidin-2-ones.

A simple synthesis of 10-deacetoxytaxol derivatives

Abstract The C-10 oxygen substituent can be reductively removed in high yield by reaction of taxol, baccatin III, or 10-deacetylbaccatin III with samarium diiodide. This reaction pathway can be completely shut down by protection of the C-7 hydroxyl group of baccatin III as the triethylsilyl ether.

Direct one step mono-functionalisation of symmetrical 1,2-diols

The mono-functionalisation of meso- and C2-symmetric diols has been achieved via the use of a new lanthanide(III) chloride catalysed acylation reaction.

In vitro efficacy of a novel chemoradiopotentiator— taxoltere metro

PURPOSE To evaluate the in vitro cytotoxic and radiopotentiating effects of a novel paclitaxel analog (taxoltere metro) on Chinese hamster ovary (CHO) cells and human colon cancer cells. METHODS AND MATERIALS Three cell lines (CHO cells, HCT116 human colon carcinoma cells [paclitaxel-sensitive], and VM46 cells [paclitaxel-resistant subline of HCT116]) were employed in this study. Cell survival was determined using the standard colony-forming assay. The ID50 value (drug concentrations required to reduce colony formation to 50% of the control value) was determined as a cytotoxic index from each cell survival curve. The sensitizer enhancement ratio (SER) as a radiopotentiating endpoint was determined as the ratio of the D0 values (with or without drugs) under hypoxic or air conditions. RESULTS Taxoltere metro was 5-15 times more effective in killing CHO cells than paclitaxel under both hypoxic and euoxic treatment conditions. Cytocidal effects of taxoltere metro on HCT116 cells and VM46 cells were 28 and 70 times higher than those of paclitaxel (p<0.001), respectively. Taxoltere metro also produced significant radiopotentiating effects on euoxic CHO and HCT116 cells, but not on hypoxic cells. The SER value of taxoltere metro for CHO cells was about 2.3 at a dose of 100 nM. With HCT116 cells, taxoltere metro yielded an SER of 1.2 at the low dose of 10 nM. In contrast, the parent compound paclitaxel yielded little or no radiosensitization with either CHO or HCT116 cells. CONCLUSION The results demonstrate that taxoltere metro is significantly more potent than paclitaxel in chemoradiopotentiating CHO cells and HCT116 human colon carcinoma cells. The data strongly suggest that taxoltere metro could be a promising chemoradiopotentiating agent for treatment of cancer.