9-amino-4,5-diazafluorene-9-carboxylic acid (Daf), a new C-alpha,C-alpha-disubstituted glycine containing a spatially constrained bipyridine-like ligand for transition metals - Synthesis and evaluation of peptide-coupling conditions at its C- and N-termini

Acylation of the anion of N-benzyl-8,5-diazafluorene-9-methyleneamine with methyl or benzyl chloroformate, followed by acidic hydrolysis, resulted in 9-amino-4,5-diazafluorene-9-carboxylic acid methyl eater (H-Daf-OMe) and be nzyl ester (H-Daf-OBz1), respectively N-alpha-protection with Boc(2)O at 60 degreesC gave Boc-Daf-OMe and Boc-Daf-OBz1, saponification or hydrogenolys is of which resulted in complete decarboxylation. However, hydrazinolysis o f the ester function afforded Boc-Daf-NHNH2, which was efficiently coupled with H-Ala-OMe by the acylazide method. Coupling of Boc-Ala-OH at the N-ter minus of Daf could also be performed by the mixed anhydride method. However , coupling of the crowded Aib residue required the use of Boc-Aib-NCA. Daf, a new C-alpha,C-alpha-disubstituted glycine, is the first alpha -amino aci d containing a rigid bipyridine ligand in a totally controlled spatial disp osition relative to the C-alpha atom.