Asymmetric synthesis of ES-285, an anticancer agent isolated from marine sources

The asymmetric synthesis of (2S,3R)-2-amino-3-octanedecanol hydrochloride (ES-285·HCl) was achieved in eight steps in ca. 38 % overall yield from the N-benzylimine-derived from (R)-2,3-O-isopropylidene glyceraldehyde, which is easily available on gram scale from the inexpensive precursor D-mannitol. Highly diastereoselective addition of methylmagnesium bromide to the N-benzylimine was the key step to create the vic-amino alcohol moiety with the appropriate configuration. Regioselective ring opening of an intermediate aminoepoxide enabled the introduction of the long hydrocarbon chain at C4.Financial support of the Spanish Ministry of Science and Innovation and European Regional Development Fund (CTQ2008-00187/BQU) and the Government of Aragón (GA E-71) is acknowledged.Peer reviewe