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Importantly, reporting nausea and stopping treatment because of it are very different only about 4.3% discontinued for GI reasons in the STEP trials

This methodology opens the way to (3 S ,4 S )-3-hydroxy-4-methoxy- ( 104 ) and 3,4-dimethoxy-L-glutamic acid ( 105 ) since selective opening of the lactone ring in 95 can be accomplished by boron trifluoride etherate-catalyzed methanolysis at low temperatures to give dimethyl ester 98 (Scheme 25)