Abstract: A molecular conjugate is provided having the formula: wherein R1 is a de-hydroxyl or de-amino moiety respectively of a hydroxyl-bearing or amino-bearing biologically active molecule or an analog or derivative thereof, and Z is —O— or —NH—, respectively, Y is a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups; and R2 is —CH?CH(W), —CH(OH)CH(OH)W, or —C(O)H, where W can be H, a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups.

Abstract: A molecular conjugate is provided having the formula: wherein n is the conjugation number, P is a moiety of a carrier molecule such as a protein, R1 is a moiety of a biologically active molecule or its analogs, derivatives, salts or secondary amines, Z is —O— or —NH—, and Y is a straight or branched alkyl having 1 to 20 carbons optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl, electron-withdrawing or electron-donating groups. Compounds and methods useful in producing such molecular conjugates are also provided, as well as methods of concentrating biologically active molecules in selected target cells of a patient that comprise administering to the patient a selected dose of such molecular conjugates.

Abstract: A method is provided for processing a solution having optical isomers to obtain a (2R,3S) target isomer: wherein P1 is H or a hydroxyl protecting group, R1 is H, an alkyl group, an olefinic group or an aromatic group, and R2 is H or R3CO, where R3 is an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group or an O-aromatic group, provided that R1 is not H when R3 is Ph and P1 is H. The method includes passing the solution through a chromatographic stationary phase, such as S,S Whelk-O, that has a greater affinity for one of the target isomer and an optical isomer thereof. A portion of the solution with the target isomer is then collected. The solution may be a racemic mixture of (±)-N-CBZ-3-phenylisoserine ethyl ester.

Abstract: A composition and method of treating multiple myeloma are disclosed. The composition and method utilize brusatol, bruceantin, glaucarubolone, and derivatives thereof as active multiple myeloma treating agents in mammals, including humans.

Abstract: A method is provided for processing a solution having optical isomers to obtain a (2R,3S) target isomer: 1

Abstract: A molecular conjugate is provided having the formula: 1

Abstract: A composition and method of cancer treatment is disclosed. The composition and method utilize brusatol, bruceantin, glaucarubolone, and derivatives thereof as active cancer treating agent in mammals, including humans.

Abstract: The present invention describes a process for producing 10-deacetyl baccatin III from a solution containing a solvent reactive with hydrazine hydrate and a spectrum of taxanes. The solution is contacted with hydrazine hydrate thereby converting some taxanes therein into 10-deacetyl baccatin III. The process can target taxanes having an ester functionality on at least one of the C-10 and C-13 positions. The hydrazine hydrate cleaves the ester functionality of the taxane solute, The process may be used to produce 10-deacetyl baccatin III from a biomass extract by contacting the biomass extract with a mixture of a solvent and a hydrazine hydrate. The solvent may have a functional group that is cleaved by hydrazine. Acetate solvents are contemplated.

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 the steps of deprotecting the 7-O-position, 3′-N-position and 2′-O-position thereof in the presence of an acid to form a first intermediate compound having a formula: wherein HA is said acid, and benzoylating the first intermediate compound at the 3′-N-position thereby to produce paclitaxel.

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: The present invention describes a process for producing 10-deacetyl baccatin III from a solution containing a solvent reactive with hydrazine hydrate and a spectrum of taxanes. The solution is contacted with hydrazine hydrate thereby converting some taxanes therein into 10-deacetyl baccatin III. The process can target taxanes having an ester functionality on at least one of the C-10 and C-13 positions. The hydrazine hydrate cleaves the ester functionality of the taxane solute. The process may be used to produce 10-deacetyl baccatin III from a biomass extract by contacting the biomass extract with a mixture of a solvent and a hydrazine hydrate. The solvent may have a functional group that is cleaved by hydrazine acetate. Acetate solvents are contemplated.

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 process for producing 10-deacetyl baccatin III from an acidic solution containing a spectrum of taxanes, comprising contacting the acidic solution containing the spectrum of taxanes with a hydrazine hydrate, thereby to convert into 10-deacetyl baccatin III some taxanes in said solution that are not 10-deacetyl baccatin III.

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.

Abstract: Methods of obtaining renewable sources of taxanes including taxol are provided. Compositions comprising taxanes which are useful as source materials for the further purification of taxanes are also disclosed. Specifically, a method of drying plant matter to preserve their taxane content and facilitate their extraction is disclosed. In addition, methods of extracting and purifying taxol and other taxanes from ornamental cultivars using a series of organic and aqueous solvents and normal phase chromatography columns are also disclosed.