Abstract: 2-debenzoyl-4-deacetyl paclitaxel, antineoplastic analogs thereof and intermediates are taught, as well as the formation of the compound, analogs and intermediates. The compound, analogs and intermediates may be used to form pharmaceutical compositions having anti-neoplastic activity. Further, the compound, analogs and intermediates may be used to treat cancer when applied in an effective amount by means such as a pharmaceutical composition.

Abstract: Novel oxazolidines finding utility as intermediates in the preparation of C-13 acyloxy sidechain-bearing taxanes such as paclitaxel and analogs thereof. The present invention also relates to novel methods of coupling the oxazolidines to form the aforementioned taxanes, and to methods of preparing the oxazolidines.

Abstract: An antitumor compound of formula (5): Also provided by the present invention is a method of preparing a compound of formula (5) whereby diesterification of the alcohol groups located at the 2′and 7 positions of paclitaxel is followed by the hydrolysis of the 2′hexanoate group resulting in 7-hexanoyltaxol.

Abstract: A process for the purification of paclitaxel and/or cephalomannine and/or 10-DAB III and/or 9-DHAB III is described. A series of extractions, separations, and purifications provides these products in commercial quantities with high purity. The source for these natural products is from readily available renewable biomaterials, such as leaves and stems from the yew, T. canadensis.

Abstract: A process for the purification of paclitaxel and/or cephalomannine and/or 10-DAB III and/or 9-DHAB III is described. A series of extractions, separations, and purifications provides these products in commercial quantities with high purity. The source for these natural products is from readily available renewable biomaterials, such as leaves and stems from the yew, T. canadensis.

Abstract: Highly specific biocatalytic reactions have been used to create a population of taxol derivatives.

Abstract: The present invention relates to a method of producing a taxane-type diterpene wherein a cell and/or a tissue of a plant which produces the taxane-type diterpene is cultured in the presence of at least one substance selected from the group consisting of coronatines, a bacterium which produces the coronatines, a culture solution or a culture extract of such bacterium, cyclic polysaccharides, fatty acids, and an imino or amino derivative of jasmonic acids, then the taxane-type diterpene is recovered from the resulting cultures.

Abstract: Taxane derivatives having an alkyl substituted C13 side chain.

Abstract: Taxane derivatives having alternative C7 substituents.

Abstract: A taxoid of formula (7), a method for making the taxoid, a pharmaceutical composition containing the taxoid, and a method for treating tumors by administering the taxoid: wherein R1 is a branched or unbranched C3-C5 alkyl or alkenyl radical, CF2H, or (S)-2,2-dimethylcyclopropyl; R8 is a C1-C4 alkyl radical; and R7 is F, Cl, MeO, vinyl, Me, or N3.

Abstract: A method for the continuous synthesis of baccatin-III is performed by means of the enzymatic acetylations of 10-deacetyl baccatin-III (10-DAB) in an enzyme reactor. This objective is accomplished by a method, for which an aqueous reaction batch is used, which contains a partially purified or a very pure acetyl transferase from a Taxus species and synthesis components, especially 10-DAB, acetyl compounds or optionally an acetyl coenzyme A, which can be regenerated, a protective colloid and optionally a buffer substance in solution. The solution is separated by a semipermeable membrane from an organic solvent, which serves as extraction agent for baccatin-III, the reaction batch being regenerated at regular intervals in an aqueous buffer system and the solvent continuously being exchanged. By conducting the reaction, the product can be removed continuously from the reaction batch for the partial synthesis of taxol and taxoter. By the above method, achievable yields are increased significantly.

Abstract: A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal or an ammonium alkoxide is reacted with a &bgr;-lactam.

Abstract: The present invention provides a novel semi-synthetic method of producing a variety of novel taxane derivatives. The method involves the reaction of a phenylisoserine derivative with a suitably blocked Baccatin III derivative to produce a taxane substrate that may be further modified to form Pactitaxel and other potentially useful taxane derivatives.

Abstract: The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions thereof, and their use as antitumor agents.

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: A process for the extraction and purification of Paclitaxel from a natural source of taxanes, comprising extracting Paclitaxel with an organic solvent from a natural source of taxanes, and treating the raw material with a base or an acid to obtain a biomass by precipitation. The biomass is isolated and dried, and resin and natural pigments are removed. The biomass is then dissolved in acetone and at least one non-polar solvent is added, until a Paclitaxel-enriched oily phase is obtained. The Paclitaxel-enriched oily phase is then treated with a base or an acid to obtain a second biomass, which is recovered by precipitation and dried. A solution of the second biomass in a volatile solvent is chromatographically purified at least once and crystallized.

Abstract: The present invention relates to a semi-synthetic process to convert a naturally occurring taxane into a suitable starting material for the synthesis of paclitaxel and related compounds. Specifically, the present invention relates to a process for the conversion of 9-dihydro-13-acetylbaccatin III into a 7-protected baccatin III which can then be used as starting material for the synthesis of taxane derivatives such as paclitaxel, docetaxel, cephalomannine and other taxanes structurally related to baccatin III. The method as described uses a preparative scale technique which is amenable to commercial scale-up.

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 discloses a process for the conversion of a mixture of taxol analogues 7-xylosyl-10-deacetylbaccatin taxols of the formula 2 where R is C6H5, CH3C═CHCH3 or C5H11 into 10-deacetylbaccatin III of the formula 1 by dissolving the taxol analogue of formula 2 in a polar solvent, reacting the resultant solution with a base at a temperature of 20-50° C. for a time period in the range of 20-40 hours, and isolating 7-xyloxyl-10-deacetylbaccatin III, dissolving the 7-xylosyl-10-deacetylbaccatin III in a polar solvent, reacting the resultant solution with a periodate at 20-40° C. for a time period in the range of 20-40 hours to cleave the diol system of the xyloside into dialdehyde, treating the generated dialdehyde in an organic acid medium with salts of amine at 0-40° C. for 12-18 hours and isolating 10-deacetylbaccatin III of formula 1.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: An enzymatic hydroxylation method for the preparation of compounds useful as intermediates in the preparation of taxanes such as 6-&agr;-hydroxy-7-deoxypaclitaxel, wherein one or more C-6 hydrogen-bearing taxanes are contacted with an enzyme or microorganism capable of hydroxylating said C-6 carbon to give C-6 hydroxyl-bearing taxane.

Abstract: This invention is directed to novel halogenated paclitaxel derivatives, processes for their preparation and use as effective anti-tumor agents.

Abstract: The present invention discloses a method for producing a taxane-type diterpene(s) by culturing cells of a taxane-type diterpene-producing plant, comprising one or both of the the following steps (a) and (b) to increase the ratio of those cell clusters suitable in size for diterpene production: (a) at least one operation for removing large cell clusters is conducted with a sieve and/or a filter during preculture of the cells to be supplied to main culture for the production of taxane-type diterpenes or at the time of cell transfer from one preculture to the subsequent preculture; (b) the cells are cultured under strong agitation conditions.

Abstract: A naphthalene derivative, binaphthalene derivative and biphenyl derivative, all having an oxetane group, capable of being cationically polymerized and a cationically curable compound containing a naphthalene derivative having an oxetanyl group and an aromatic compound having an epoxy group or an oxetanyl group.

Abstract: In an assay method in which a member of a specific binding pair is detected by means of an optically detectable reaction, the improvement wherein the optically detectable reaction includes the reaction, with an enzyme, of a dioxetane having the formula 1

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods.

Abstract: Taxane derivatives having an amino substituted C13 side chain.

Abstract: Compounds having the formula: wherein T is a polycycloalkylidene group (e.g., adamant-2-ylidene); R is a C1-20 alkyl, aralkyl or cycloalkyl group; and Y is a fluorescent chromophore (e.g., m-phenylene), produced by reacting a compound having the formula: with an R-ylating agent (e.g., R2 SO4) in the presence of an alkali metal alkoxide in a polar aprotic solvent. Also, compounds having the formula: are produced by reacting a compound having the formula: with wherein X is an electronegative leaving group (e.g., a halogen anion such as chloride ion) in the presence of a Lewis base (e.g., a trialkyl-amine) dissolved in an aprotic organic solvent (e.g., benzene or toluene). Also, compounds having the formula are produced by reacting a compound of the formula with a tetra-O-acylated-O-hexopyranoside halide, then hydrolyzing off the protective acyl groups.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: Methods of preparing methylthiomethyloxy taxoids of formula (XXXIV) 1

Abstract: Stable, enzymatically triggered chemiluminescent 1,2-dioxetanes with improved water solubility and storage stability are provided as well as synthetic processes and intermediates used in their preparation. Dioxetanes further substituted with two or more water-solubilizing groups disposed on the dioxetane structure and an additional fluorine atom or lower alkyl group provide superior performance by eliminating the problem of reagent carryover when used in assays performed on capsule chemistry analytical systems. These dioxetanes display substantially improved stability on storage. Compositions comprising these dioxetanes, a non-polymeric cationic surfactant enhancer and optionally a fluorescer, for providing enhanced chemiluminescence are also provided.

Abstract: The object of the invention is to develop baccatin derivatives useful for preparing taxoid compounds such as paclitaxel and a process for the producing the same. The invention provides baccatin derivatives represented by the general formula (I) as well as a process for producing baccatin derivatives represented by the general formula (I) above, which comprises allowing a baccatin represented by the general formula (II) to react with a &bgr;-ketoester in the absence of a catalyst or in the presence of a tin compound or an amine base, preferably under reduced pressure.

Abstract: The present invention relates to a new taxane having the structure as in Formula I, and its analogs as depicted in Formula II and Formula III. The invention includes novel semi-synthetic and isolation methods for the preparation of these novel taxanes. Specifically, the present invention relates to the new taxane Canadensol isolated from plants of the Taxus genus in particular, Taxus canadensis. The present invention further relates to the use of these new taxanes as anticancer agents.

Abstract: Taxanes having a carbamoyloxy substituent at C(10), a hydroxy substituent at C(7), and a range of C(2), C(9), C(14), and side chain substituents.

Abstract: 4-Benzoylpyrazoles of the formula I where: R1 and R2 are each hydrogen, mercapto, nitro, halogen, cyano, thiocyanato, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, —OR10, —OCOR10, —OSO2R10, —S(O)nR10, —SO2OR10, —SO2NR3R10, —NR10SO2R10 or —NR10COR; Q is a pyrazole of the formula II,  which is attached in position 4 and, Substituted 4-benzoylpyralozoles.

Abstract: This invention relates to a method of producing a taxane-type diterpene(s) wherein tissues or cells of a plant which produces taxane-type diterpene(s) is cultured in the presence of at least one selected from the group consisting of jasmonic acids, compounds containing a heavy metal, complex ions containing a heavy metal, heavy metal ions, amines and antiethylene agents, a method of producing a taxane-type diterpene wherein the tissues or the cells of the plant are cultured by controlling the oxygen concentration in a gas phase in a culture vessel to less than the oxygen concentration in the atmosphere from the initial stage of the culture, or by controlling the dissolved oxygen concentration in a fluid medium which is in contact with the tissue or the cell to less than the saturated dissolved oxygen concentration at that temperature from the initial stage of the culture, a method of producing a taxane-type diterpene wherein the tissue or the cell of the plant is cultured in a culture vessel, while oxygenic g

Abstract: The present invention is a method of preventing or reducing atherosclerosis or restenosis, and a pharmaceutical preparation used therefor. In particular, it is a method of preventing or reducing atherosclerosis or restenosis after arterial injury by treatment with a low dose of a microtubule stabilizing agent such as taxol or a water soluble taxol derivative. The low dose used in the present invention prevents artery blockage while minimizing any negative side effects associated with the drug.

Abstract: The present invention relates to novel intermediates for the hemisynthesis of taxanes and to their processes of preparation. The compounds of the present invention include precursor compounds of taxane side chains.

Abstract: Taxanes having a heterosubstituted acetate substituent at C(10), a hydroxy substituent at C(7), and a range of C(2), C(9), C(14), and side chain substituents.

Abstract: The present invention is directed to photoresist cross-linkers selected from the group consisting of a cross-linker monomer represented by following Chemical Formula 1, and homopolymers and copolymers thereof. wherein X1, X2, R, R′, R″, R1, R2, p, q and s are those defined herein. Such cross-linkers are suitable for use in photolithography processes employing KrF(248 nm), ArF(193 nm), E-beam, ion-beam or EUV light sources.

Abstract: Taxanes having a heterosubstituted acetate substituent at C(7), a hydroxy substituent at C(10), and a range of C(2), C(9), C(14), and side chain substituents.

Abstract: The invention provides novel paclitaxel derivatives obtained by effecting modifications at C2′, C3′ and/or C7 positions of paclitaxel, said derivatives being useful in inhibiting the growth of cancer of lung, breast, ovary, cervix or leukemia, and pharmaceutical compositions comprising such derivatives.

Abstract: Provided herein is a taxane having a hydrocarbon attached at the 2′ and/or 7 positions, the hydrocarbon's alpha position being occupied by a “hydrolysis-promoting group” (“HPG”). In one embodiment, the hydrolysis promoting group is stereospecifically attached to the a-carbon of the hydrophobic taxane. The Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers or inflammatory diseases.

Abstract: This invention relates to novel processes for making (2S, 3S, 5S) oxetanone derivative lipase inhibitor compounds and intermediates therefor, which processes for producing such derivatives that are useful as lipase inhibitors are capable of being scaled to commercial quantities. Further the invention relates to processes for producing salts and for producing pharmaceutical compositions compounds comprising at least one such oxetanone derivative or salt, as well as methods for using such compounds and compositions for inhibiting lipases.

Abstract: Taxane derivatives having alternative C2 substituents.

Abstract: New taxoids of general formula (I): their preparation and pharmaceutical compositions containing them. The new products of general formula (I) in which Z represents a radical of general formula (II): display noteworthy antitumour and antileukaemic properties.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: The present invention relates to chemical compounds that are useful in the production of taxanes.

Abstract: Provided herein is a taxane having a hydrocarbon attached at the 2′ and/or 7 positions, the hydrocarbon's alpha position being occupied by a “hydrolysis-promoting group” (“HPG”). In one embodiment, the hydrolysis promoting group is stereospecifically attached to the &agr;-carbon of the hydrophobic taxane. The Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers or inflammatory diseases.

Abstract: A method for extracting taxanes such as taxol, comprising the use of supercritical fluids.