Paclitaxel (I) was protected as the 2'-(triethylsilyl) derivative (II) and then converted to the 7-methylsulfanylmethyl ether (III) by treatment with dimethyl sulfide and benzoyl peroxide. Subsequent desilylation of (III) using aqueous acetic acid or HCl in H2O/CH3CN furnished the desired 7-O-methylsulfanylmethyl paclitaxel. Alternatively, the title compound was also obtained by direct methylsulfanylmethylation of paclitaxel.
The reaction of 10-O-deacetyl-baccatin III (I) with triethylsilyl chloride and pyridine gives the 7-O-silyl derivative (II), which is acylated with Ac2O and pyridine to yield 7-O-(triethylsilyl)baccatin III (III). The condensation of (III) with the chiral oxazolidine-carboxylic acid (IV) by means of DCC and DMAP in ethyl acetate affords the 13-O-ester (V), which is desilylated by means of HF and TEA in dichloromethane to provide the free 7-hydroxy derivative (VI). The reaction of (VI) with dimethylsulfoxide, Ac2O and HOAc gives the 7-O-(methylsulfanylmethyl) derivative (VII), which is finally hydrolyzed at the oxazolidine ring by means of HCl in ethyl acetate to give rise to the target 7-O-(methlsulfanylmethyl)taxol.
The reaction of 10-O-deacetyl-baccatin III (I) with triethylsilyl chloride and pyridine gives the 7-O-silyl derivative (II), which is acylated with Ac2O and pyridine to yield 7-O-(triethylsilyl)baccatin III (III). The desilylation of (III) by means of HCl in ethanol yields baccatin III (VIII), which is condensed with DMSO by means of Ac2O and HOAc to afford the ketonic derivative (IX). The reduction of (IX) by means of NaBH4 in ethanol affords 7-O-(methylsulfanylmethyl)baccatin III (X), which is condensed with the chiral azetidinone (XI) by means of LiHMDS in THF to provide 2'-O-(1-ethoxyethyl)-7-O-(methylsulfanylmethyl)taxol (XII). Finally, this compound is deprotected by means of HCl in ethanol to give the target 7-O-(methylsulfanylmethyl)taxol.
The reaction of 10-O-deacetyl-baccatin III (I) with triethylsilyl chloride and pyridine gives the 7-O-silyl derivative (II), which is acylated with Ac2O and pyridine to yield 7-O-(triethylsilyl)baccatin III (III). The condensation of (III) with the chiral azetidine (XI) by means of LiHMDS In THF affords 2'-O-(1-ethoxyethyl)-7-O-(triethylsilyl)taxol (XIII), which is treated with HF and pyridine to provide the desilylated taxol derivative (XIV). The reaction of (XIV) with DMSO, Ac2O and HOAc gives the 2'-O-protected 7-O-(methylsulfanylmethyl) derivative (XII), which is finally deprotected by means of HCl in ethanol to yield the target 7-O-(methylsulfanylmethyl)taxol.