An efficient semi-synthetic approach utilizing the appropriately functionalized (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone (4) and 7-(p-azidobenzoyl)baccatin III (3) is described which leads to the targeted biologically active taxol photoaffinity label 6. Taxol (1), a naturally occurring diterpene isolated from the bark of the Pacific yew,1,2 exhibits remarkably high anticancer/antitumor activity.3,4 Now in clinical trials in the United States, it appears to be one of the most exciting antitumor agents recently developed.5-7 Taxol elicits its biological activity through an unique mechanism of tubulin assembly promotion and subsequent polymer stabilization effects which ultimately leads to cell death.8 Although these effects are well documented, little is known about the precise mode of binding or topography of the taxol binding site on tubulin.8,9 Photoaffinity labels have been utilized extensively in the determination of binding orientations of organic molecules to biologically important receptors.10 Aryl azides are an important group of photoaffinity labels and are convenient to prepare. Utilizing semi-synthetic methodology developed in our laboratories toward the synthesis of taxol and taxol analogues,11-13 we report the semi-synthesis of a novel taxol photoaffinity label. Other reports of approaches to14 and semi-synthesis15 of taxol photoaffinity labels have appeared recently in the literature. Reports of minor decreases in biological activity of taxol derivatives possessing substituents at the C-7 hydroxyl group15-17 had prompted us to pursue the synthesis of the 7-(p-azidobenzoyl)taxol affinity label. The aryl azide located at the C-7 hydroxyl group of the molecule should allow, through labeling studies, the characterization of the binding site of taxol in tubulin. These studies may provide information for the elucidation of the precise mechanism of binding of taxol to microtubules.7-(p-Azidobenzoyl)taxol (6) was prepared by utilizing both the availability of the naturally occurring taxane, 10-deacetyl baccatin III,18 and the precedented synthesis of the C-13 phenylisoserine side chain via the ester enolate-imine condensation of (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone previously reported from our laboratory.12 7-(p-Azidobenzoyl)baccatin III (3) (Scheme 1) was prepared by esterification of baccatin III (2)18,19 with p-azidobenzoic acid in the presence of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP). The DCC/DMAP esterification takes advantage of the relative reactivity of the C-7 hydroxyl group in comparison to the C-13 hydroxyl group and the virtually unreactive C-1 hydroxyl group.20 The esterification proceeded in 53% yield with no diesterification evident. A diastereomeric mixture of the ethoxyethyl (EE) protected (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone 411,13 was coupled21 to baccatin III derivative 3 in the presence of pyridine and DMAP to afford taxol derivative 5 in 55% yield. Quantitative deprotection of the coupled product 5 by acid hydrolysis using 0.5% HCl in EtOH at 0 °C led to photoaffinity label 6.21