A Ring and Its Substitutions

When C-13a ester hnkage was substituted by amide or epimerized to P form, reduced or loss of activity was observed. Chen et al. initially failed to transform 

Except for the C-13 substitutions, the most extensively studied in A ring modifications are contracted ring (A-nor), opened ring (A-seco), and the 11,12-dihydro analogs. Although some derivatives showed comparable activities, most of them were less active than paclitaxel. 

A C-11,12 double-bond rearranged product 24 was observed when 2, 7- i/-Troc-10-deacetyl paclitaxel was treated with Yarovenko reagent (Et2NCF2CHFCl), which can be then transformed into 2 -Troc-10-deoxy paclitaxel (25) by catalytic hydrogenation, along with the formation of a small amount of 12-fluorinated 26. All taxoids, after deprotection, showed reduced cytotoxicity seven to eight times. 

It has been found that the C-11,12 double bond in paclitaxel was resistant to many reaction conditions, including catalytic hydrogenation and ozonolysis. Harriman et al. reasoned that C-10 acetate may hamper the epoxidation from the p-face and the cupshaped core structure prevents the epoxidation from the ot-face. By removal of 10-acetate in paclitaxel, the 11,12-p-epoxide was formed quantitatively. The 11,12-epoxidized taxoid 27 was only one third as cytotoxic as paclitaxel against B16 melanoma cells. The 11,12 double bond in baccatin was reducible by zinc in acidic conditions. Since treatment of 11,12-dihydro baccatin 28b with base only yielded 13-acetyl-4- 

12- dihydrodocetaxel was almost inactive. Because of the poor activity of the documented 4-deacetyl taxoids, it is not sure if the inactivity has developed from the reduction of 11,12-olefin. Considering another report (see Section 3.2.2.1), the 

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