Stereoselective synthesis of C2 - C10 fragment of Rhizoxine-D

ORGN 176

Javed Iqbal, javediqbaldrf@hotmail.com1, Srinivas Padakanti, psriniva@drreddys.com2, K Mukkanti, kmukkanti@rediffmail.com3, and Manojit Pal, manojitpal@dreddys.com2. (1) Discovery Chemistry, Discovery Research, Miyapoor, Bollaram road, Hyderabad-500049, India, (2) Discovery Chemistry, Discovery Research, Dr. Reddy's Laboratories, Ltd, Miyapoor, Bollaram road, Hyderabad-500049, India, (3) Department of Chemistry, JNT University, Kukatpally, Hyderabad 500072, India
Synthesis of C2-C10 fragment of Rhizoxine-D was carried out in a stereoselective fashion to afford the corresponding 5(S)-diastereomer (B1) for the first time. Two of the three chiral centers of B1 were generated from readily available TBS protected methyl(R)-3-hydroxy-2-methylpropionaldehyde using Brown's allylation, followed by esterification and finally by usinig Grubb's ring closing metathesis to afford the Α Β - &Delta unsaturated lactone. Michael addition on this lactone with lithium diallyl cuparate resulted a key intermediate C having anti C5, C7 conformation. Conversion of C to B1 was achieved via Dess-Martin oxidation followed by Takai reaction. The synthesis of 5(R)-diastereomer(B2) will be discussed.