Towards the synthesis of Rhizoxine D: A stereo selective synthesis of C1-C16 core

ORGN 732

Javed Iqbal, javediqbaldrf@hotmail.com1, Srinivas Padakanti, psriniva@drreddys.com1, Manojit Pal, manojitpal@dreddys.com1, and K. Mukkanti, kmukkanti@rediffmail.com2. (1) Discovery Chemistry, Discovery Research, Dr. Reddy's Laboratories, Ltd, Bollaram road, Miyapur, Hyderabad, 500049, India, (2) Chemistry Division, Institute of Science &Technology, JNT University, JNTU, Kukatpally, Hyderabad, 500072, India
Rhizoxine D is a highly cytotoxic 16- membered macrolide was isolated from the fungus Rhizopus Chinesis by Iwasaki and coworkers1. It exhibits excellent antimitotic activity , through binding to beta-tubulin, against most eucarytotic cells. The exciting biological activity and well-functionalized macrolide structure led us to undertake the synthesis of this molecule. Here we describe an efficient and stereoselective synthesis of C1-C15 core of Rhizoxine D that was achieved by using a common intermediate 1-benzyloxy-2-methyl-hex-5-en-3-ol. The key steps of this synthesis are stereoselective Michael addition, Thakai olifination and inter molecular Heck reaction.

 

Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006