Total Syntheses of (+)-Hypusine and Its (2S,9S)-Diastereomer

Article abstract of DOI:10.1021/jo00076a048

The total synthesis of (2S,9R)-hypusine dihydrochloride, an unusual amino acid constituent of the eukaryotic translation initiation factor eIF-4D, and its (2S,9S) diastereomer is described.The key step in the syntheses involves Nε-alkylation of Nε-benzyl-Nα-(L)-lysine benzyl ester with (R)- or (S)-epichlorhydrin to give the respective (2S,9R) and (2S,9S) chlorohydrins.Subsequent displacement of the respective chlorides by cyanide ion provides the protected hypusine skeletons.The final step, hydrogenation over PtO2 in AcOH followed by neutralization and reacidification, yielded the respective (2S,9S)- and (2S,9R)-hypusine dihydrochlorides in excess of 50percent overall yield.