Abstract: The present invention relates to a method of producing paclitaxel from a protected coupled ester compound having a formula: wherein P1 is a hydrogenatable protecting group, comprising deprotecting the 7-O-position and 3′-N-position of the protected coupled ester compound to form a first intermediate compound, benzoylating the first intermediate compound at the 3′-N-position thereby to form a second intermediate compound, and deprotecting the second intermediate compound by replacing P1 with hydrogen in the presence of an acid. The present invention also provides chemical compounds useful in the production of paclitaxel.

Abstract: The present invention relates to a method of producing paclitaxel or a paclitaxel analog comprising the esterification of C-7, C-10 di-CBZ 10-deacetylbaccatin III with an N-carbamate protected, C-2-protected 3-phenyl isoserine side chain. The C-7, C-10 carbobenzyloxy groups are then replaced with hydrogen and an acyl group is substituted at the C-3′ nitrogen. The resulting compound is acylated at the C-10 hydroxyl position, and deprotected at the C-2′ position by replacing the hydroxyl protecting group with hydrogen to produce paclitaxel or a paclitaxel analog. The present invention also relates to alternative methods of acylating a 10-hydroxy paclitaxel analog. The first method comprises dissolving a 10-hydroxy paclitaxel analog in an acceptable ether solvent therefor to form a first solution at a first temperature.

Abstract: A chemical compound comprising an isotopically labeled analog of a standard taxane molecule, wherein said isotopically labeled analog is synthetically formed to have incorporated therein at a selected position a stable isotope of an element existing at said selected positon in said standard taxane molecule, said isotope having amass different form a mass of a mass of a most abundantly occurring isotope of said element in nature, such that said isotopically labeled analog has a molecular weight different form a molecular weight of said standard taxane molecule.

Abstract: A chemic compound having the formula: ##STR1## wherein P.sub.1 is a hydroxyl protecting group, R.sub.1 is an alkyl group, an olefinic group, an aromatic group, Ph, PhCH.sub.2, an O-alkyl group, an O-olefinic group, an O-aromatic group, O--Ph, or O--CH.sub.2 Ph, and wherein Z is an N-imido group. In particular, P.sub.1 may be selected from the group consisting of benzyl, benzyloxymethyl and benzoyl, and Z may be a heterocyclic N-imido group, preferably having 5 to 7 atoms in the ring and alternatively substituted with at least one electron withdrawing group, preferably selected from the group consisting of a chloro group, a fluoro group and a nitro group. In particular, it is contemplated that Z may be succinimido, phthalimido, 5-norbornene-2,3-dicarboxyimido, maleimido and substituted derivatives thereof.

Abstract: A chemical compound having the formula: ##STR1## wherein P.sub.1 is a hydroxyl protecting group, R.sub.1 may be H or electron withdrawing group, R.sub.2 may be H or electron withdrawing group, R.sub.3 may be H or electron withdrawing group, R.sub.4 may be H or electron withdrawing group, R.sub.5 may be H or electron withdrawing group, R.sub.6 may be an alkyl group, an olefinic group, an aromatic group, Ph, PhCH.sub.2, an O-alkyl group, an O-olefinic group, an O-aromatic group, O--Ph, or O--CH.sub.2 Ph.

Abstract: A method of acylating C-2' O-protected-10-hydroxy taxol selectively at the C-10 hydroxyl position over the C-7 hydroxy position thereof to produce C-2' O-protected taxol is accomplished first by dissolving C-2' O-protected-10-hydroxy taxol in an acceptable ether solvent therefor, such as tetrahydrofuran, to form a first solution at a first temperature. The first solution is then cooled to a second temperature, and a lithium base, preferably n-butyl lithium, is added to form an intermediate compound having a lithium alkoxide at the C-10 position thereof. An acylating agent, such as acetyl chloride, is then added. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent and the lithium base. The result is a solution containing C-2' O-protected taxol. This solution may then be washed, concentrated and purified. The present invention is also directed to C-10 lithium alkoxide intermediate compounds for the production of paclitaxel.

Abstract: A method of acylating C-2' O-protected-10-hydroxy taxol selectively at the C-10 hydroxyl position over the C-7 hydroxy position thereof to produce C-2' O-protected taxol is accomplished first by dissolving C-2' O-protected-10-hydroxy taxol in an acceptable ether solvent therefor, such as tetrahydrofuran. A lithium salt, preferably lithium chloride, is added. A trialkylamine base or pyridine is next added, followed by the addition of an acylating agent, such as acetyl chloride. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent. This solution may then be diluted with ethyl acetate to form an organic phase and an aqueous phase, with the organic phase being washed and thereafter reduced. Recrystallization and column chromatography may be employed to purify the C-2' O-protected taxol.

Abstract: A method of acylating 10-deacetylbaccatin III at the C-10 position over the C-7 hydroxy position thereof to produce baccatin IIII is accomplished first by dissolving 10-deacetylbaccatin III in an acceptable ether solvent therefor, such as tetrahydrofuran. A lithium salt, preferably lithium chloride, is added. A trialkylamine base or pyridine is next added, followed by the addition of an acylating agent, such as acetyl chloride. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent. The result is baccatin III in solution. This solution may then be diluted with ethyl acetate to form an organic phase and an aqueous phase, with the organic phase being washed and thereafter reduced. Recrystallization and column chromatography may be employed to purify the baccatin III.