Vitamin C and Isovitamin C Derived Chemistry. 2. Synthesis of Some Enantiomerically Pure 4,5,6-Trihydroxylated Norleucines

Article abstract of DOI:10.1021/jo00382a022

A sequence leading to enantiomerically pure 4,5,6-trihydroxylated norleucines 23-25, their 5,6-O-isopropylidene derivatives 17a,b and 20, and lactones 19a,b and 22 from relatively inexpensive carbohydrate precursors is described. 5,6-O-Isopropylidene-L-gulono-, -D-mannono-, and -D-galactono-1,4-lactones (2a,b and 7b) react readily with 2 equiv of mesyl chloride in pyridine at 0 deg C to produce hex-2-enono-1,4-lactone 2-mesylates 5a,b and 8.The butenolides are stereoselectively reduced to 3-deoxyhexono-1,4-lactone 2-mesylates 11a,b and 12, which are then treated with sodium azide in DMF to generate the configurationally C-2-inverted azides 15a,b and 16.Hydrogenation thereof, in the presence of triethylamine, gives the 5,6-O-isopropylidenated title compounds 17a,b and 20, which are hydrolyzed in boiling water to give amino acids 23-25 and are converted into lactones 19a,b and 22 by treatment with dilute hydrochloric acid under reflux.The lactones are optimally produced directly from 15a,b and 16 by hydrogenation in the presence of acid.