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.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)