Related Experiment Videos
Practical synthesis of chiral emopamil left hand as a bioactive motif
Teiji Kimura1, Noboru Yamamoto, Yuichi Suzuki
1Tsukuba Research Laboratories, Eisai Company, Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 3002635, Japan. t2-kimura@hhc.eisai.co.jp
Abstract:
An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.