SIDE REACTIONS IN PEPTIDE-SYNTHESIS .12. HYDROGENOLYSIS OF THE 9-FLUORENYLMETHYLOXYCARBONYL GROUP

When an attempt was made to selectively remove the benzyl ester group from (9-fluoroenylmethyloxycarbo-nyl)-α-benzyl-L-aspartic acid a-(2,4,5-trichlorophenyl ester) by Pd-catalyzed hydrogenation, parallel to the disappearance of the starting material, formation of a nin-hydrin-positive compound was noted. This prompted a second experiment in which a solution of (9-fluorenyl-methyloxycarbonyl)-L-alanine (FMOC-L-Ala) in methanol was hydrogenated in the presence of a small amount of acetic acid and a 10% Pd-on-charcoal catalyst. Under similar conditions Carpino and Han80 recovered an FMOC derivative unchanged. Yet, in our experiment after h of hydrogenation at 0 °C we could not detect the starting material, FMOC-L-alanine, but found instead free alanine. These observations were surprising because the resistance of the FMOC protecting group to hydrogenolysis was emphasized in the papers which introduced this new method of protection and was mentioned again in the literature.81 In an attempted reduction of FMOC-aniline Carpino and Han recovered the starting material unchanged, while benzyl carbanilate, also present in the mixture, was completely cleaved. Because of these conflicting results we carried out additional experiments. First, we subjected FMOC-glycine to catalytic hydrogenation and found complete removal of the protecting group. © 1979, American Chemical Society. All rights reserved.