Taxol (paclitaxel) and docetaxel are highly effective anticancer drugs but have undesired side effects and multidrug resistance (MDR). Thus, developing new anticancer drugs with improved properties is important. 14β-Hydroxy-10-deacetylbaccatin III (14β-OH-DAB), isolated from Taxus wallichiana Zucc., has higher water solubility than 10-deacetylbaccatin III (DAB), making it a promising precursor for new taxoids with better pharmacological properties. A series of new taxoids (5a, 5b, 7a, 7b) were synthesized from 14β-OH-DAB using a highly efficient β-lactam synthon method. Cytotoxicity assays showed these new taxoids possess strong cytotoxicities against human breast, non-small cell lung, ovarian, and colon cancer cell lines. Specifically, 5a exhibits better activity than paclitaxel against non-small cell lung cancer (A549) and colon cancer (HT-29) cell lines, and shows substantial activity against adriamycin-resistant breast cancer (MCF7-R) cells. Attachment of the N-acylphenylisoserine side chain at C-14 instead of C-13 (as in 7a) results in a ~10-fold decrease in cytotoxicity, but 7a still retains 10 nM level IC50 cytotoxicities. Molecular modeling reveals that the energy-minimized structure of 7a overlaps excellently with that of docetaxel, suggesting it can mimic docetaxel's binding conformation to tubulin. Microtubule disassembly inhibitory activities relative to paclitaxel are 0.9T (5a), 3T (5b), >50T (7a), and >100T (7b). In vivo, 5a shows equivalent or slightly better activity than paclitaxel against A151 human ovarian carcinoma xenografts in nude mice, causing total tumor regression. Further investigations on the structure-activity relationships (SAR) of these new taxoids are ongoing.