Patent ID: 6593482
Filing Date: 2003-07-15
Classification: A61P,C07D

Abstract:
A method of preparing (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropionate of 4,10&bgr;-diacetoxy-2&agr;-benzoyloxy-5&bgr;,20-epoxy-1,13&agr;-dihydroxy-7&bgr;-methylthiomethyloxy-9-oxo-tax-11-ene, formula (XXXIV): comprising:silylating a baccatin of formula (IX): â€ƒto obtain a silylated baccatin, wherein the silylation occurs at position 7; acetylating said silylated baccatin to obtain a silylated baccatin III of formula (XXX): removing the silyl group to obtain baccatin III with a 7-hydroxy group; or, alternatively, directly acetylating the baccatin of formula (IX) to obtain baccatin III with a 7-hydroxy group; reacting said baccatin III with a 7-hydroxy group, wherein said reacting may include more than one reaction step, including an optional reduction reaction, to generate a compound of formula (A): â€ƒwherein R is hydrogen; performing a metalation of said compound of formula (A) with an alkali metal or alkaline earth metal base, to produce a metalized methylthiomethyl-baccatin III derivative of formula (A), wherein R is an alkali metal or alkaline earth metal; coupling said metalized methylthiomethyl-baccatin III derivative of formula (A) with a protected &bgr;-lactam, wherein said protected &bgr;-lactam comprises a &bgr;-lactam of formula: â€ƒwherein Y is oxygen; G1 is an hydroxyl protecting group; R2â€³ is phenyl; and R3â€³ is phenyl; â€ƒto produce a 2â€²-protected 7-methylthiomethyl-paclitaxel derivative; and deprotecting said 2â€²-protected 7-methylthiomethyl-paclitaxel derivative by removing G1 to produce a compound of formula (XXXIV).