Hauser, Inc.

The Johns Hopkins University

Other

Hauser Chemical Research, Inc.

Qun Y Zheng

Christopher K Murray

Randall J Daughenbaugh

Gary H Posner

Poonsakdi Ploypradith

Lynn G Darbie

Sagar R Shakya

Theresa A Shapiro

Xiaoqin Cheng

S Kent Peterson

Michael H Parker

Soon Hyung Woo

Jeffrey S Elias

John Northrop

7-hexanolytaxol and methods for preparing the same

7-hexanoyltaxol and methods for preparing the same

The present invention provides a two-step procedure for the replacement of the pyranose anomeric 10-OH group in dihydroartemisinin by a variety of carbon nucleophiles, resulting in the novel C-10 carbon-substituted trioxanes of structure: ##STR1## wherein, when n is 1, R is selected from a group of unsubstituted or substituted aryls, heteroaryls, polyethylene glycol, acetylenics, or benzoylmethylenes, or alkanoylmethylenes; or when n is 2, R is selected from a group of unsubstituted or substituted aryls, heteroaryls, polyethylene glycol, alkenyls, alkyls, diketones or bis-acetylenes; or when n is 3, R is selected from a group of unsubstituted or substituted aryls, heteroaryls, polyethylene glycol, alkenyls, alkyls, diketones or bis-acetylenes.

C-10 carbon-substituted artemisinin-like trioxane compounds having

The present invention provides a two-step procedure for the replacement of the pyranose anomeric 10-OH group in dihydroartemisinin by a variety of carbon nucleophiles, resulting in the novel C-10 carbon-substituted trioxanes of structure: ##STR1## wherein, when n is 1, R is selected from a group of unsubstituted or substituted aryls, heteroaryls, polyethylene glycol, acetylenics, or benzoylmethylenes, or alkanoylmethylenes; or when n is 2, R is selected from a group of unsubstituted or substituted aryls, heteroaryls, polyethylene glycol, alkenyls, alkyls, diketones or bis-acetylenes.

An antitumor compound of formula (5) ##STR1## and 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.

Novel trioxane dimers of structure ##STR1## which possess antiproliferative and antitumor activities.

Trioxane dimer compounds having antiproliferative and antitumor

An antitumor compound of formula (5) ##STR1## in which R is Ac or H, and R.sub.1, R.sub.2 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu, R.sub.3 is H; R.sub.1 and R.sub.2 and R.sub.3 are H; R.sub.1 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu, R.sub.2, R.sub.3 is H; R.sub.1 and R.sub.3 are H, R.sub.2 is an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu; R.sub.1 is H, R.sub.2 and R.sub.3 are an alkyl group such as Me, Et, Pr, i-Pr, n-Bu or t-Bu; R.sub.1 and R.sub.2 and R.sub.3 are an alkyl group Me, Et, Pr, i-Pr, n-Bu or t-Bu. Me is an abbreviation for methyl, Et is ethyl, Pr is propyl, i-Pr is isopropyl, n-Bu is n-butyl, and t-Bu is tert-butyl. Also provided by the invention is a one step method of preparing a compound of formula (5) whereby a taxane having a tiglate group attached to the side chain is contacted with an oxidizing reagent resulting in the formation of an epoxide having antitumor activity.

Cephalomannine epoxide, its analogues and a method for preparing the same

Novel artemisinin dimers of structure ##STR1## which possess anticancer activity.

Artemisinin dimer compounds having anticancer activity

Described herein are novel trioxane dimers of structure ##STR1## which possess antiproliferative and antitumor activities.

The invention relates to a process for converting Taxol A, B and C to Taxol primary amine which can then be easily and efficiently converted to Taxol A or docetaxel, thereby significantly increasing the yield of these products from biomass. The method includes the removal of the amide from the side-chain with Schwartz's reagent to form an imine, followed by the hydrolysis of the imine to the primary amine. The primary amine can then be converted to Taxol A or docetaxel. New Taxol imine compounds and primary amine salts have been formed by this process.

Preparation of Taxol and docetaxel through primary amines

Preparation of taxol and docetaxel through primary amines

Disclosed herein are novel artemisinin dimers of structure ##STR1## which possess anticancer activity.

The present invention relates to a highly selective method for the deacetylation and deacylation of taxol and taxanes compounds. Specifically, the present invention relates to a one step process wherein acyl groups located at the carbon 2', 10, and 7 positions of taxol and other taxane compounds may be selectively removed.

Selective process for the deacylation and deacetylation of taxol and

The present invention relates to a process for converting purified, partially purified or crude taxane mixtures into a protected precursor of 10-deacetylbaccatin III and into 10-deacetylbaccatin III. The process comprises three steps, the first of which includes contacting a mixture containing at least one naturally occurring taxane compound having the structure (II) ##STR1## in which R.sub.1 is phenyl, ##STR2## [an ester linkage at the C-13 position] with at least one hydroxy protecting group. The second step involves cleaving the ester linkage of the protected taxane thus giving rise to a protected precursor of 10-deacetylbaccatin III, the deprotection of which leads to 10-deacetylbaccatin III.

Growing community of inventors

Wayne, NJ, United States of America

Qun Y Zheng