Syntheses of Bile Pigments. Part 17. Synthesis of a non‐racemizable urobilin derivative

The optically active urobilin model compound 7 was synthesized, in which Me groups instead of H-atoms are bound to the asymmetric centers, thus preventing loss of chirality by tautomerization. The key intermediate of the eleven-step synthesis of 7 is the 1,4,5,10-tetrahydro-10-hydroxy-1-oxo-11H-dipyrrin-9-carboxylate rac-2, which could be resolved into enantiomers by fractional crystallization of the corresponding methyl N-[1-(naphth-1-yl)ethyl]carbamates 3 and 4. The absolute configuration of enantiomerically pure (−)-2 was determined by X-ray diffraction analysis of its camphor-10-sulfonate 5. As the CD spectrum of the urobilin analogue 7 obtained from (−)-(R)-2 displays a positive Cotton effect, the present results prove, in connection with previous work, that substitution of Me groups for the H-atoms bound to the asymmetric centers of a chiral urobilin chromophore do not influence the relationship between absolute configuration of the latter and its helicity.