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Published on: July 28, 2022
An Efficient Synthesis of 4(5)-Benzyl-L-Histidines Employing Catalytic Transfer Hydrogenolysis at Elevated
D David Smith1, Audrey T Gallagher2, Vincent M Crowley2
1Department of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha, NE 68178, U.S.A.
Abstract:
An efficient two-step synthesis of 4(5)-benzyl-L-histidine from L-histidine was developed. A Pictet-Spengler reaction between L-histidine and benzaldehyde in the presence of excess strong base yielded 4-phenylspinacine within one hour. Catalytic transfer hydrogenolysis in methanol at reflux using ammonium formate rapidly converted 4-L-phenylspinacine to 4(5)-benzyl-L-histidine within five minutes. No racemization of the final product 4(5)-benzyl-L-histidine was observed using the Marfey reagent. To show the utility of this methodology, a series of fluorinated benzylhistidines is presented.
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