Patent ID: 6465221
Filing Date: 2002-10-15
Classification: C07C,C12N,C12P

Abstract:
A method of producing a taxane ring containing alkaloid compound wherein a cell and/or a tissue of a plant belonging to the genus Taxus, which produces the taxane ring containing alkaloid compound, is cultured in the presence of an effective taxane ring containing alkaloid compound producing amount of at least one substance selected from the group consisting of:A) a compound in a concentration of 0.001 to 1000 &mgr;M of the formula X: â€ƒwherein Y is: i) a hydrogen atom, ii) a hydroxyl group, iii) a cyano group, iv) NR28aR28b, wherein R28a and R28b independently are a hydrogen atom, carbamoyl group, acyl group having 1 to 12 carbon atoms, alkyl group having 1 to 12 carbon atoms, alkylsulfonyl group having 1 to 12 carbon atoms, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl, OR29, wherein R29 is an acyl group having 1 to 12 carbon atoms, alkyl group having 1 to 12 carbon atoms, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl, â€”COâ€”R30, wherein R30 is a hydrogen atom, amino group or alkylamino group having 1 to 12 carbon atoms; or v) alkyl group having 1 to 12 carbon atoms, aminosulfonyl group, alkylsulfinyl group having 1 to 12 carbon atoms, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; R1a, R1b, R1c, R1d, R1e and R1f independently are a hydrogen atom; hydroxyl group; alkyl group having 1 to 12 carbon atoms; alkoxy group having 1 to 12 carbon atoms; aryl group; substituted aryl group; arylalkyl group; or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; R1a and R1c optionally form a double bond or R1c and R1e optionally form a double bond or R1e and R1f optionally form a double bond; R20, R21, R22, R23 and R24 independently are a hydrogen atom; hydroxyl group; alkyl group having 1 to 12 carbon atoms; aryl group; substituted aryl group; arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; a side chain consisting of C1â€”C2â€”C3â€”C4â€”C5â€”C6 which has one or more double bonds;R25 is: i) a hydroxyl group, ii) OM, wherein M is an alkaline metal atom, alkaline earth metal atom or NH4, iii) NR26aR26b, wherein R26a and R26b independently are a hydrogen atom, acyl group having 1 to 12 carbon atoms, alkyl group having 1 to 12 carbon atoms, amino acid residue, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; iv) OR27, wherein R27 is an alkyl group having 1 to 12 carbon atoms, carbohydrate residue, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; or v) an alkyl group having 1 to 12 carbon atoms, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; n is an integer of 1-7; and B) a compound in a concentration of 0.001 to 1000 &mgr;M of the formula XI: â€ƒwherein R1a, R1b, R1c, R1d, R1e, R1f and R1g independently are a hydrogen atom; hydroxyl group; alkyl group having 1 to 12 carbon atoms; alkoxy group having 1 to 12 carbon atoms; aryl group; substituted aryl group; arylalkyl group; or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; R1a and R1c optionally form a double bond or R1c and R1e optionally form a double bond or R1e and R1f optionally form a double bond or R1f and R1g optionally form a double bond or R1a and R1g optionally form a double bond; R20, R21, R22, R23 and R24 independently are a hydrogen atom; hydroxyl group; alkyl group having 1 to 12 carbon atoms; aryl group; substituted aryl group; arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; a side chain consisting of C1â€”C2â€”C3â€”C4â€”C5â€”C6 which has one or more double bonds;R25 is: i) a hydroxyl group, ii) OM, wherein M is an alkaline metal atom, alkaline earth metal atom or NH4, iii) NR26aR26b, wherein R26a and R26b independently are a hydrogen atom, acyl group having 1 to 12 carbon atoms, alkyl group having 1 to 12 carbon atoms, amino acid residue, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; iv) OR27, wherein R27 is an alkyl group having 1 to 12 carbon atoms, carbohydrate residue, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; v) alkyl group having 1 to 12 carbon atoms, aryl group, substituted aryl group, arylalkyl group or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; R31a and R31b independently are a hydrogen atom; hydroxyl group; acyl group having 1 to 12 carbon atoms; alkyl group having 1 to 12 carbon atoms; alkoxy group having 1 to 12 carbon atoms; amino acid residue; aryl group; substituted aryl group; arylalkyl group; or substituted arylalkyl group, wherein said aryl group or substituted aryl group is phenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl or naphthyl, and wherein said arylalkyl group or substituted arylalkyl group is benzyl, p-methoxybenzyl, p-chlorobenzyl or p-fluorobenzyl; then the taxane ring containing alkaloid compound is recovered from resulting cultures of the cell and/or tissue of a plant.