Scheme 1.

Synthesis of alkylaminoluciferins. a) Reductive alkylation of intermediate 3a afforded acyclic alkylaminoluciferins; b) Attempts to form cyclic alkylaminoluciferins from 3a gave exclusive formation of the undesired 6’,7’-fused isomer (e.g., 8); c) Synthesis of 5’,6’-fused cyclic alkylaminoluciferins 16 required reversal of the order of ring formation. i) HNO₃, H₂SO₄; ii) SnCl₂-2H₂O, EtOH, reflux; iii) NaBH(OAc)₃, 37% HCHO, DCE, HOAc; iv) KCN, DMSO, 130°C; v) D-Cys, aq. MeOH, pH 8; vi) 5 mol% In(OTf)₃, acetone, rt; vii) TFAA, TEA, rt; viii) KSCN, Br₂, AcOH, rt; ix) t-BuONO₂, CuCl, CH₃CN; x) NaBH₄, EtOH.