戴维斯氧氮杂环丙烷介导的不对称合成质子泵抑制剂使用.pdfVIP

Organic Process Research Development 2010, 14, 1264–1268 Davis Oxaziridine-Mediated Asymmetric Synthesis of Proton Pump Inhibitors Using DBU Salt of Prochiral Sulfide Rajendra D. Mahale,* Mahesh R. Rajput, Golak C. Maikap,* and Mukund K. Gurjar Emcure Pharmaceuticals Ltd, R D Centre, Plot No.12/2, F-II Block, M.I.D.C., Pimpri, Pune - 411018, India Abstract: enantioselective sulfoxidation developed by Kagan et al. and A simple and clean asymmetric synthesis of proton pump inhibi- Modena et al.5-7 von Unge et al. suitably modified Kagan’s tors using inexpensive 10-camphorsulfonyl oxaziridine is described. method and successfully extended this methodology to prepare Here, we report the activation of prochiral sulfide by making the esomeprazole with 55% yield.15 However, there are intrinsic DBU salt that is capable of enhancing the reactivity and issues with this method, the foremost being the formation of enantioselectivity. sulfone. The complex formation involving sulfide, titanium isopropoxide, water, and (S,S)-diethyl tartrate and oxidation in the presence of N,N-diisopropylethylamine are crucial steps. The Introduction author clearly mentions that enantioselectivity is dramatically Optically pure sulfoxides are not only utilized as chiral decreased when DBU is used as the base. Several metal- auxiliaries in asymmetric synthesis but they also constitute part catalyzed methods are also reported for the synt