The Synthesis of Carbohydrate α-Amino Acids Utilizing the Corey–Link Reaction

Abstract

Various carbohydrate ketones (uloses) have been treated with chloroform under strongly basic conditions to yield trichloromethyl tertiary alcohols. These alcohols, when subjected to the conditions of the modified Corey–Link reaction (sodium azide and 1,8-diazabicyclo[5.4.0]undec-7-ene in methanol), generally gave the expected azido ester with complete stereocontrol. Subsequent transformations on these azido esters provided amino esters, azido acids, and, in one case, the amino acid. A similar sequence applied to a protected d-glucono-1,5-lactone was only partly successful.

Single-crystal X-ray structures are reported for 1,2:5,6-di-O-isopropylidene-3-C-trichloromethyl-α-d-allose, (3S)-3-C-azido-3-C-carboxy-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-ribo-hexose, 1,2:5,6-di-O-cyclohexylidene-3-C-trichloromethyl-α-d-gulose, (3S)-3-C-amino-1,2:5,6-di-O-cyclohexylidene-3-deoxy-3-C-methoxycarbonyl-α-d-xylo-hexose, methyl 2-O-benzyl-4,6-O-benzylidene-3-C-trichloromethyl-α-d-alloside, methyl (2S)-2-C-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-C-methoxycarbonyl-α-d-arabino-hexoside, methyl 2,3-di-O-benzyl-6-deoxy-4-C-trichloromethyl-β-d-galactoside, 3,4,5,7-tetra-O-benzyl-1,1,1-trichloro-1-deoxy-α-d-gluco-hept-2-ulose, and 5-O-benzyl-1,2-O-isopropylidene-3-C-trichloromethyl-α-d-ribose.