The preparation of simplified scyphostatin analogues using a tethered aminohydroxylation (TA) strategy

The first tethered aminohydroxylation reaction employing a tertiary alcohol is reported as part of a route to prepare analogues of the naturally occurring sphingomyelinase inhibitor, scyphostatin. The tethered aminohydroxylation of 1-allylcyclohexanol produces the β-amino alcohol product, in protected form, with the required regiochemistry. Two approaches to the installation of the lipophilic side chain are described and the successful route used to prepare five novel scyphostatin analogues, one containing the natural lower side chain.