Synthesis of Flavin-Indole Conjugates with Rigid Diamino Linkers as Cryptochrome Model Compounds

Abstract

The synthesis of flavin-indole conjugates with a trans-1,4-diaminocyclohexane and a 2,6-diaminodecahydronaphthalene linker is reported. Both compounds should serve as artificial model compounds for natural cryptochrome. It is assumed that cryptochrome photoreceptor proteins located in the retina show a light-dependent quantum effect which enables migratory birds to perceive the Earth's magnetic field and is thus used for navigation. Both model compounds were prepared by stepwise reductive aminations of indole carbaldehyde and a flavin-substituted acetaldehyde with the appropriate diamine linkers. The hitherto unknown 2,6-diaminodecahydronaphthalene was prepared in four steps from 2,6-dihydroxynaphthalene as the achiral (meso) ax,ax,trans-diastereoisomer. The configuration of this key intermediate as well as synthetic precursors has been established by a series of X-ray single crystal analyses.