Total Synthesis of (±)-Halomon by a Johnson-Claisen Rearrangement

Thierry Schlama; Rachid Baati; Véronique Gouverneur; Alain Valleix; John R Falck; Charles Mioskowski

doi:10.1002/(SICI)1521-3773(19980817)37:15<2085::AID-ANIE2085>3.0.CO;2-J

Total Synthesis of (±)-Halomon by a Johnson-Claisen Rearrangement

Angew Chem Int Ed Engl. 1998 Aug 17;37(15):2085-2087. doi: 10.1002/(SICI)1521-3773(19980817)37:15<2085::AID-ANIE2085>3.0.CO;2-J.

Authors

Thierry Schlama¹, Rachid Baati¹, Véronique Gouverneur¹, Alain Valleix², John R Falck³, Charles Mioskowski¹

Affiliations

¹ Université Louis Pasteur, Faculté de Pharmacie, Laboratoire de Synthèse Bioorganique associé au CNRS, 74, route du Rhin, BP-24, 67401 Illkirch (France), Fax: (+33) 3-88-67-88-91.
² CEA Saclay, Service des Molécules Marquées, Bat. 547, Département de Biologie Cellulaire et Moléculaire, F-91191 Gif-sur-Yvette (France).
³ Department of Biochemistry, Southwestern Medical Center, University of Texas, 5323 Harry Hines Blvd., Dallas, TX 75235-9038 (USA).

Abstract

The total synthesis of the polyhalogenated antitumour agent halomon (1) was accomplished with two novel transformations as key steps: a Johnson-Claisen rearrangement of a dichlorinated alkene for the preparation of the tertiary chlorinated C3 and a new rearrangement of bromohydrins for the regiospecific introduction of the bromine and chlorine atoms on C6 and C7, respectively.

Keywords: Antitumour agents; Halomon; Natural products; Rearrangements; Total synthesis.