The Synthesis of Two Furan‐Based Analogues of the α′,β′‐Epoxy Ketone Proteasome Inhibitor Eponemycin

Myers’s methodology for enantioselective amino acid synthesis was employed to prepare the N‐Boc didehydroleucine amide derivative 15 and to effect its conversion into the acylfuran intermediate 17. Coupling of 19 (R = H) with N‐(isooctanoyl)serine provided the furan‐based analogue 4 of eponemycin (de = 96 %), a peptide epoxide with potent cytotoxic and anti‐angiogenesis properties. In an identical fashion the corresponding unsaturated analogue 5 of eponemycin was prepared (de = 48 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003