7-TES-baccatin III

Shiina I, Saitoh K, Frechard-Ortuno I, Mukaiyama T (1998) Total Asymmetric Synthesis of Taxol by Dehydration Condensation between 7-TES Baccatin III and Protected N-Benzoylphenylisoserines Prepared by Enantioselective Aldol Reaction. Chem Lett 3... 

Some approaches for the semisynthesis of taxol are based on relatively economically priced 10-deacetylbaccatin III, obtained from leaves of the European yew Taxus baccata. The leaves are able to regenerate by growing again, whereas removal of the bark of the Pacific yew Taxus brevijblia, which contains taxol, kills the tree. The semisyntheses of Denis and Greene from 1988 [190] and 1994 [191] are discussed here. 10-Deacetylbaccatin III 257 is first protected at the 7-position with a triethyl-silyl residue and acetylated at the 10-position with acetyl chloride. The resulting 7-TES-baccatin III 258 is coupled with O-protected N-benzoyl-3-phenylisoserine using a sixfold excess of dipyridyl carbonate (DPC) to afford 2 -0-ethoxyethyl-7-TES-taxol 259, which is deprotected with 0.5% hydrochloric acid to afford taxol 241 [190]. 

Holton claimed in a patent application that (3/ ,45)-A-benzoyl-3-0-EE-(3-lactam 11 (5 equiv), obtained through tedious classical optical resolution of racemic t (. -3-hydroxy-4-phenylazetidin-2-one, could be directly coupled with 7-TES-bac-catin III (8) in the presence of 4-dimethylaminopyridine (DMAP) and pyridine and the subsequent deprotection afforded paclitaxel in ca. 82% yield.54 Although this procedure was proved to work by us and by others, the use of a large excess of (3-lactam is obviously inefficient. Moreover, the Holton procedure did not work at all when /V-f-Boc-(3-lactam 12 was used for our attempted syntheses of docetaxel and its 10-acetyl analogue. This is due to the lack of reactivity of the A-r-Boc-(3-lactam 12 toward the C-13 hydroxyl group of a protected baccatin III under the Holton conditions. The lack of reactivity is ascribed to the substantially weaker... 

With regard to the modification of the C-2 benzoate, several methods were reported for the introduction of other aryl or hetero-aromatic groups. However, those methods turned out to be not compatible to our purpose, which required modifications at C-2 as well as C-3. The successful routes to 2-modified baccatins 44 and 45 using 13-oxo-7-TES-DAB (41)72 are illustrated in Scheme 11.44 We also used 7-TES-(hexahydro)baccatin III (19) for the synthesis of 3 -modified 2-cyclo-hexanecarbonyl taxoids. 

Hydroxylation of enolate generated from 7-TES-13-oxobaccatin III 267 with various A -sulfonyloxaziridines, 33, (+)-146, and (+)-202, were studied by Baldelli et al. <2003JOC9773>. 7-TES-13-oxo-14/30H-baccatin III 268 was obtained in 83-88% yield. The yield and diastereoselectivity of the hydroxylation were not affected by the choice of oxaziridine, indicating that the stereoselectivity was substrate controlled. 

A,0-Bis(trimethylsilyl)trifluoroacetamide. This reagent is suitable for the silylation of carboxylic acids, alcohols, phenols, amides, and ureas. It has the advantage over bis(trimethylsilyl)acetamide in that the by-products are more volatile. It has been used for the selective protection of 10-desacetyI-baccatin III using LHMDS as a catalyst. The TES and TBDMS ethers were prepared similarly. Conventional conditions using the silyl chloride results in silylation of the C-7 hydroxyl ... 

---