Convergent synthesis of macrolide core of (-)-16-normethyldictyostatin

ORGN 649

Parthasarathi Das, parthasarathi@drreddys.com1, V Saibaba, vsbaba@drreddys.com1, Javed Iqbal, javediqbaldrf@hotmail.com1, and K Mukkanti, parthads@yahoo.com2. (1) Discovery Research, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India, (2) Chemistry Division, Institute of Science and Technology, JNT University, Kukatpally, Hyderabad, 500072
Macrolides remain as good synthetic targets due to their structural diversities, biological activities and important medicinal properties. (-)-Dictyostatin (1a) is a sponge-derived macrolactone and a potent antitumor agent that acts by microtubule stabilization. Among the many possible analogues we have focused our attention on the synthesis of (-)-16-normethyldictyostatin which is equally potent to its parent (-)-dictyostatin. The synthesis of the 22-membered macrolide core (2) of (-)-16-normethyldictyostatin envisaged the preparation of C10-C23 fragment (3) via cross metathesis between 5 and 6. Diastereoselective coupling of C10-C23 (3) with C1-C9 (4) fragment which was synthesized by Evans aldol condensation and (Z)-olefination followed by Yamaguchi lactonisation produced the macrolide 2.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

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