Simple approach to γ-hydroxy-α,β-(E)-alkenoic esters: Application to the synthesis of macrolides

ORGN 125

K. Srinivasa Rao, javediqbaldrf@hotmail.com1, D. Srinivasa Reddy1, Manojit Pal1, K. Mukkanti, javediqbaldrf@hotmail.com2, and Javed Iqbal1. (1) Discovery Research, Dr. Reddy’s Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500 049, India, (2) Chemistry Division, Institute of Science&Technology, Kukatpally, Hyderabad, 500 072, India, JNT University, Kukatpally, Hyderabad, 500 072, India, Hyderabad, 500 072, India
We have developed a simple procedure for the synthesis of γ-hydroxy-α,β-(E)-alkenoic esters from corresponding acetylenic esters using LiAlH4 as hydride source. The utility of resulting γ-hydroxy-α,β-(E)-alkenoic esters was readily demonstrated by the synthesis of various macrolides of pharmacological importance. We have used commercially available (S)-ethyl lactate as the starting material for the synthesis of all the macrolides shown below.