150250-95-6Relevant articles and documents
Highly chemoselective trichloroacetimidate-mediated alkylation of ascomycin: A convergent, practical synthesis of the immunosuppressant L- 733,725
Song, Zhiguo,DeMarco, Anthony,Zhao, Mangzhu,Corley, Edward G.,Thompson, Andrew S.,McNamara, James,Li, Yulan,Rieger, Dale,Sohar, Paul,Mathre, David J.,Tschaen, David M.,Reamer, Robert A.,Huntington, Martha F.,Ho, Guo-Jie,Tsay, Fuh-Rong,Emerson, Khateeta,Shuman, Richard,Grabowski, Edward J. J.,Reider, Paul J.
, p. 1859 - 1867 (2007/10/03)
L-733,725, a new immunosuppressant drug candidate, was prepared by a highly chemoselective alkylation of the macrolide ascomycin at the C32 hydroxy position with the imidazolyl trichloroacetimidate 16. The trichloroacetimidate-activated side chain 16 was prepared by an efficient fourstep sequence in 42% overall yield. The high chemoselectivity in the alkylation of the C32 hydroxy group of the unprotected ascomycin was the result of the synergetic effects of the electron-donating protecting group on the imidazole 16, the polar, moderately basic solvent, and the strong acid catalyst. N,N-Dimethylpivalamide mixed with acetonitrile was found to be the best solvent and trifluromethanesulfonic acid the best catalyst. This synthesis coupled with a resin column purification of L-733,725 followed by crystallization of its tartrate salt has been used to make multikilogram quantities of the bulk drug with consistent and high purity.
