The Scripps Research Institute

Tokyo University of Science, Center for Science and Technology Exchange

Mitsuru Shoji

Kyriacos Costa Nicolaou

Karl-Heinz Altmann

Yujiro Hayashi

Andreas Ritzen

Trond Ulven

Kenji Namoto

The invention relates to cis- and trans-12, 13-cyclopropyl and 12,13-cyclobutyl epothilones of formula I to IV wherein Ar is a radical represented by the following structure: and the other radicals and symbols have the meanings as defined herein; to their chemical synthesis and biological evaluation; their use in the treatment of neoplastic diseases and to pharmaceutical preparations containing such compounds. The compounds described herein are potent tubulin polymerization promoters and cytotoxic agents.

Cyclopropyl and cyclobutyl epothilone analogs

The corresponding &#x3b1;-aminooxy ketone is manufactured with a high yield and a high enantioselectivity. A manufacturing method for an optically active &#x3b1;-aminooxy ketone derivative expressed by formula (1), wherein a ketone expressed by formula (2) is caused to react with a nitroso compound expressed by formula (3) in the presence of a proline derivative expressed by formula (4). In the formula, Rand Rrespectively denote an alkyl, alkenyl or alkynyl group, and Rand Rmay be linked to form a ring. Rdenotes an aryl, heterocyclic, alkyl, alkenyl or alkynyl group. A denotes a hydrogen atom, alkoxy group, aryloxy group, acyloxy group or silyloxy group which may have a substituent.

Optically active &#x3b1;-aminooxyketone derivatives and process for production thereof

Growing community of inventors

Tokyo, Japan

Mitsuru Shoji