A concise synthesis of (−)-cytoxazone and (−)-4- epi-cytoxazone using chlorosulfonyl isocyanate

Abstract

A concise synthesis of (−)-cytoxazone and its stereoisomer (−)-4- epi-cytoxazone, novel cytokine modulators, has been accomplished each in six steps from readily available p-anisaldehyde with good diastereoselectivity. Key steps in the synthesis include the regioselective and diastereoselective amination of anti- and syn-1,2-dimethyl ethers with chlorosulfonyl isocyanate and the subsequent regioselective cyclization of the diol to construct the oxazolidin-2-one core. The diastereoselectivity of amination reaction using CSI was explained by the Cieplak electronic model via S N1 mechanism and neighboring group effect, leading to the retention of the configuration.