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DOI: 10.1055/s-2004-837204
Access to Unnatural Glycosyl Amino Acid Building Blocks via a One-Pot Ritter Reaction
Publikationsverlauf
Publikationsdatum:
17. Dezember 2004 (online)
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Abstract
α-d-Galacto-2-deoxy-oct-3-ulopyranosonic acids, α-d-gluco-2-deoxy-oct-3-ulopyranosonic acids and α-l-galacto-2,8-dideoxy-oct-3-ulopyranosonic acids can be converted into unnatural glycosyl amino acids via a one-pot intramolecular Ritter reaction. Initially, a ketopyranoside-based acid condenses under Lewis acid-promoted conditions with a nitrile (benzonitrile or acetonitrile) and a partially protected diamino ester (Boc-DAB-Ot-Bu, Boc-Orn-Ot-Bu) to form unnatural glycosyl amino esters. The resulting glycosyl amino esters are useful building blocks for solid-phase glycopeptide synthesis. For example, the glycosyl amino acid derived by condensation of α-d-galacto-2-deoxy-oct-3-ulopyranosonic acid with benzonitrile and DAB was used to replace serine in the potent opioid peptide sequence H2N-Tyr-d-Thr-Gly-Phe-Leu-Ser-CONH2.
Key words
carbohydrates - glycopeptides - combinatorial chemistry - glycosyl amino acids - peptides
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References
It is noteworthy that these β-galactosyl amides are not accessible via acylation of the corresponding galactosyl-amine. [14]
17Yield calculation is based on the addition of the partially protected diamino ester.
18Products were identified by MS.
20Yields are based on isolated amount after reverse phase HPLC purification. Characteristic data for 22: 1H NMR (600 MHz, CD3OD, r.t.): δ = 3.93 (dd, J = 3.03 Hz, J < 1 Hz, H-6Gal), 4.02 (d, J = 9.8 Hz, H-4Gal), 6.80 (d, J = 8.4 Hz, 2 H), 7.15 (d, J = 8.4 Hz, 2 H), 7.20-7.35 (m, 4 H), 7.45-7.53 (m, 2 H), 7.55-7.62 (m, 2 H), 7.82 (d, J = 7.10 Hz, 2 H). MS (ES): m/z calcd [M + H]+: 1022.48; found: 1022.65.
25The stereochemistry at the anomeric center in 28 has not yet been determined.
26We speculate that the axial substituent at the C-4 position in mannose-configurated ulosonic acid 8 and rhamnose-configurated ulosonic acid 16 destabilizes the cyclic form and favors the open ketone form resulting in low yields of the corresponding unnatural glycosyl amino acids (Scheme [6] ).
28A 40 ms gaussian pulse with a 560 ms mixing time was used.
30Cyanoalanine and nitriles with branching at the β-position have previously been used without success in an intermolecular Ritter reaction (see ref. 29).