Asymmetric synthesis of 2-amino-1,3-diols and D-erythro-sphinganine

The asymmetric synthesis of protected 2-amino-1,3-diols (S,R)-5 starting from 2,2-dimethyl-1, 3-dioxan-5-one is described. The stereogenic centres are generated by a-alkylation using the SAMP/RAMP hydrazone methodology and diastereoselective reduction of the ketones (S)-2 with L-selectride. The resulting alcohols (S,S)-3 are converted into the amines (S,R)-4 by nucleophilic substitution with sodium azide and subsequent reduction with lithium aluminium hydride. The products are obtained in high diastereomeric and enantiomeric excesses (de greater than or equal to 96%, ee = 90-94%). By employing this methodology, the ammonium salt of D-erythro-sphinganine (R,S)-11 was synthesised starting from RAMP-hydrazone (R)-1 in 47% overall yield and with excellent diastereomeric and enantiomeric excess (de, ee greater than or equal to 96%). ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).