848347-79-5Relevant articles and documents
A new method of carbohydrate synthesis in both solution and solid phases using a special hydroxy protecting group
Komba, Shiro,Kitaoka, Motomitsu,Kasumi, Takafumi
, p. 5313 - 5329 (2007/10/03)
A new carbohydrate synthesis method using a special hydroxy protecting group (uni-chemo protection = UCP) in both solution and solid phases was developed. The UCP group was comprised of polymerized amino acid derivatives. Each hydroxyl group was protected by a UCP group with a different degree of polymerization, which allowed them to be uniquely identified. To deprotect the UCP group, one cycle of Edman degradation was performed as follows: 1) removal of the amino protecting group; 2) phenyl isothiocyanate coupling; 3) removal of the N-terminal phenyl thiocarbamoyl mono-amino acid derivative by treatment with trifluoroacetic acid; and 4) re-protection of the newly exposed amino group with a Boc group. The hydroxyl groups were deprotected successively from the UCP group with the lowest to the highest degree of polymerization by repeating this Edman degradation cycle. First, commercially available N-α-f-Boc- sarcosine, N-α-t-Boc-N-α-methyl-L-alanine, and N-α-t-Boc-L- phenylglycine were examined as UCP groups. Despite successfully protecting and selectively deprotecting the hydroxyl groups, there were problems with stability or reactivity. To address these problems, N-α-1-ethylpropylglycine was chosen as the UCP group, and we successfully synthesized two sialyl-T antigen analogues. Tri-UCP and mono-UCP were attached to the 6- and 3-positions of the D-galactosamine (GalN) derivative, respectively, using cyanuric chloride. To selectively deprotect the mono-UCP group on the 3-position of the GalN derivative, one cycle of Edman degradation was performed. As a result of this cycle, the tri-UCP on the 6-position of the GalN derivative was degraded to di-UCP, and the mono-UCP on the 3-position was selectively deprotected to yield a GalN derivative with a free 3-position. Glycosylation of this selectively deprotected free 3-position GalN derivative with a suitably protected D-galactose (Gal) derivative in which the 3-position was protected by a mono-UCP group using N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) in dichloromethane yielded the desired disaccharide in high yield in both a position- and stereoselective manner. By repeating one cycle of Edman degradation, the 3′-position-free disaccharide in which the 6-position was protected by a mono-UCP group was prepared selectively. Subsequent acetylation and a final cycle of Edman degradation (except the third and fourth steps) yielded the 6-position-free disaccharide selectively. Two disaccharides, one with a free 3′-position and another with a free 6-position, were coupled with a sialic acid donor using NIS and TfOH in acetonitrile to obtain sialyl (2→3) T and sialyl (2→6) T antigen derivatives, respectively. Solid-phase synthesis was demonstrated using polystyrene-type beads and a new linker, 2-{4-(hydroxymethyl)benzamido}acetic acid (HMBA-Gly), to synthesize Galβ (1→3) Gal from a suitably protected Gal derivative in which the 3-position was protected by mono-UCP. Solid-phase glycosylation was successfully monitored by measuring the removal of the Fmoc group, which protected the amino group on UCP, similar to the method for monitoring solid-phase Fmoc peptide synthesis. This UCP hydroxy protecting group was suitable for solid-phase synthesis, and will be the key technique in both automated oligosaccharide synthesis and oligosaccharide library synthesis. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
