Synthesis of 6-aminocyclooctanetriol, 2-amino-6 halocyclooctanediol, 3,4-dihydroxycyclooctane carboxylic acids and derivatives

Synthesis of halo- and aminocyclitols, and β-amino acid cyclitol derivatives containing eight-membered carbocycles are described starting from cis,cis-1,5- and 1,3-cyclooctadiene. Initially, cyclooctene epoxide obtained by m-CPBA of cis,cis-1,5-cyclooctadiene was the key compound in the synthesis. As a result of various chemical transformation of the cyclooctene epoxide resulted in formation of 6-acetoxy-2-azido-5-chlorocyclooctyl 4-nitrobenzoate, 2-azido-6-chlorocyclooctane-1,5-diyl bis(4-nitrobenzoate) which are not yet known in the literature. In the second part of this work, bicyclic-lactam, prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, was converted into an amino acid ester salt by hydrolysis of the ring lactam with HCl(g) in methanol. The reaction of ester salt with di-tert-butyl dicarbonate (Boc2O) gave an N-Boc ester. Oxidation of the N-Boc ester with OsO4/NMO followed by hydrolysis of N-Boc-ester diol afforded the new 3,4-dihydroxycyclooctanecarboxylic acid as a single product. Oxirane ring-opening of the N-Boc ester epoxide compound resulting from the epoxidation of the N-Boc ester with m-CPBA was carried out with various reagents. Structure of methyl (1S*,6S*,7S*,10S*)-6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate has been also determined by an X-Ray diffraction analysis.