An efficient synthesis of 4(5)-benzyl- L -histidines employing catalytic transfer hydrogenolysis at elevated temperatures

D. David Smith, Audrey T. Gallagher, Vincent M. Crowley, Wayne M. Gergens, Peter W. Abel, Martin Hulce

Research output: Contribution to journal › Article

2 Citations (Scopus)

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-l-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 method, a series of fluorinated benzylhistidines were prepared.

Original languageEnglish
Article numberSS-2013-M0680-OP
Pages (from-to)515-521
Number of pages7
JournalSynthesis
Volume46
Issue number4
DOIs
StatePublished - Feb 2014

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Hydrogenolysis
Histidine
Methanol
formic acid
Temperature

All Science Journal Classification (ASJC) codes

  • Organic Chemistry
  • Catalysis

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An efficient synthesis of 4(5)-benzyl- L -histidines employing catalytic transfer hydrogenolysis at elevated temperatures. / Smith, D. David; Gallagher, Audrey T.; Crowley, Vincent M.; Gergens, Wayne M.; Abel, Peter W.; Hulce, Martin.

In: Synthesis, Vol. 46, No. 4, SS-2013-M0680-OP, 02.2014, p. 515-521.

Research output: Contribution to journal › Article

Smith, DD, Gallagher, AT, Crowley, VM, Gergens, WM, Abel, PW & Hulce, M 2014, 'An efficient synthesis of 4(5)-benzyl- L -histidines employing catalytic transfer hydrogenolysis at elevated temperatures', Synthesis, vol. 46, no. 4, SS-2013-M0680-OP, pp. 515-521. https://doi.org/10.1055/s-0033-1340462
Smith DD, Gallagher AT, Crowley VM, Gergens WM, Abel PW, Hulce M. An efficient synthesis of 4(5)-benzyl- L -histidines employing catalytic transfer hydrogenolysis at elevated temperatures. Synthesis. 2014 Feb;46(4):515-521. SS-2013-M0680-OP. https://doi.org/10.1055/s-0033-1340462
Smith, D. David ; Gallagher, Audrey T. ; Crowley, Vincent M. ; Gergens, Wayne M. ; Abel, Peter W. ; Hulce, Martin. / An efficient synthesis of 4(5)-benzyl- L -histidines employing catalytic transfer hydrogenolysis at elevated temperatures. In: Synthesis. 2014 ; Vol. 46, No. 4. pp. 515-521.
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