Facile synthesis of Nalpha-protected-L-alpha,gamma-diaminobutyric acids mediated by polymer-supported hypervalent iodine reagent in water.

ABSTRACT

Hofmann rearrangement of Nalpha-Boc-L-Gln-OH mediated by a polymer-supported hypervalent iodine reagent poly[(4-diacetoxyiodo)styrene] (PSDIB) in water afforded Nalpha-Boc-L-alpha,gamma-diaminobutyric acid (Boc-Dab-OH, 1) in 87% yield. Nalpha-Z-derivative (Z-Dab-OH, 2) was prepared with PSDIB in 83% yield. Since the reaction of Nalpha-Fmoc-Gln-OH by this procedure did not proceed because of the insolubility of Fmoc-Gln-OH in aqueous media, we synthesized Fmoc-Dab(Boc)-OH (5) from 2 in 54% yield. Polymyxin B heptapeptide (PMBH) which contains four Dab residues was successfully synthesized in a solution-phase synthesis.