The first synthesis of racemic validoxylamine A (3) and B (4), constituents of antibiotic validamycins, is described. For construction of these types of pseudodisaccharides containing an imino linkage, a coupling reaction of the protected anhydro derivative of DL-pentahydroxy(hydroxymethyl)cyclohexane (5) with the DL-trihydroxy(hydroxymethyl) cyclohexylamine or-cyclohexenylamine (6 or 7) was undertaken. All possible diastereoisomers (four pairs of enantiomers) formed by the reaction of 5 with 6, employed for synthesis of 4, could be separated by chromatography on silica gel, and the relative configurations in two of the enantiomeric pairs, deduced on the basis of 1H NMR spectroscopy, were confirmed by identification of one pair with an authentic chiral sample 4. On the other hand, the intermediate enantiomeric pair 13a obtained by a coupling of the appropriate epoxide 5 and amine 7 underwent mainly dehydration with sulfuryl chloride in pyridine to give the pair of enantiomers 19a, one of which was the protected derivative of 3. In contrast, the diastereoisomeric pair of enantiomers 13b yielded selectively the chloride 18b, which was then transformed into the enantiomeric pair 21b by dehydrochlorination followed by deprotection.
ASJC Scopus subject areas
- Organic Chemistry