2-Benzoylamino-2-deoxy-2-hydroxymethyl-D-hexono-1,4-lactones: synthesis from D-fructose and utilization in the total synthesis of thermozymocidin (myriocin)

Abstract

2-Benzoylamino-2-deoxy-2-hydroxymethyl-D-mannonic (6) and -D-gluconic (13) acids have been synthesized from D-fructose by the following route: (i) a hydrocyanation reaction of fructosyl-p-tolylamine, (ii) acid hydrolysis of the nitrile produced, and (iii) hydrogenolysis of the tolylamino group then formed. The stereochemistry of the hydrocyanation reaction has been studied by changing both the solvents and other reaction conditions. The major (gluconic) and the minor (mannonic) epimers have been separated and characterized by chemical and spectroscopic methods.

Upon N-acylation the amino acids (6) and (13) cyclized to the corresponding 1,4-lactones (5) and (12). One of these 2-benzoylamino-2-deoxy-2-hydroxymethyl-D-hexono-1,4-lactones [the mannonic (5)], was transformed in six steps into the 2-benzoylamino-2-benzoyloxymethyl-2-deoxy-3-O-benzoyl-5-O(4-tolylsulphonyl)-D-lyxono-1,4-lactone (3), which is a key intermediate in the convergent total synthesis of the antibiotic thermozymocidin (1).