Lansoprazole sulfoxidation

Similarly, sulfides 19 and 21 were biooxidized to the corresponding enantiomerically enriched sulfoxides, (-)-pantoprazole 20 and (-)-lansoprazole 22, respectively. These biotransformation processes are still at the exploratory stage. The concentration of the substrate is generally minute — in the ppm range. As a result, this method is not suitable for large-scale processes. 

Pantoprazole is a substituted benzimidazole sulfoxide proton pump inhibitor (Fig. 11). Like other proton pump inhibitors such as lansoprazole, all chiral benzimidazoles are administered as racemic mixtures. Pantoprazole is metabolized to pantoprazole sulphone as a major metabolite, and pantoprazole sulfide as a minor metabolite (Fig. 11). The reoxidation of pantoprazole sulfide to pantoprazole occurs in vivo, resulting in chiral inversion of pantoprazole enantiomers. Significant chiral inversion occurred after intravenous and oral administration of (-F)-pantoprazole [139]. The mechanism of this inversion has not yet been identified. 

Sudalai in 2003 reported on an asymmetric version of the sulfoxidation reaction for the preparation of enantiomeri-cally enriched lansoprazole 30 employing an heterogeneous catalytic system based on the use of WO3 as a catalyst precursor (5 mol%) in the presence of hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQD)2-PYR) 31 as the chiral ligand and aqueous hydrogen peroxide as the terminal oxidant. The catalytic system applied to the sulfide 32 reported in Scheme 48.13 led to the formation of the R enantiomer of Lansoprazole 30 in 84% yield and 88% ee. 

SCHEME 48.13. Structure of lansoprazole 30 and details of the asymmetric W(VI) sulfoxidation step. 

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