Total Synthesis of Caprazol

Key words

Sharpless asymmetric amino­-hydroxylation - glycosylation - glycosyl fluoride

Significance

Caprazol is the core structure of the Caprazamycin antibiotics. The Caprazamycins are isolated from Streptomyces sp MK730-62F2. They inhibit Mra Y, a key enzyme in peptidoglycan synthesis in Mycobacterium tuberculosis. They have no significant toxicity to mice.

Comment

Key steps in the 18-step synthesis of Caprazol were (a) a Sharpless asymmetric aminohydroxylation reaction which converts A to B; glycosylation using a 5-aminoribosyl fluoride C; and (c) a reductive amination to create the diazepa­none ring. The stereochemistry of the difficult glycosylation depended strongly on the steric bulk of the 3-pentylidene protecting group and the Lewis acid activator. With BF₃·OEt₂ at -30 °C, the anomeric ratio was α:β = 4:96.