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Asymmetric Synthesis of 2‐Amino‐1,3‐diols and D ‐ erythro ‐Sphinganine
Author(s) -
Enders Dieter,
MüllerHüwen Anke
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300788
Subject(s) - chemistry , diastereomer , hydrazone , alkylation , enantiomeric excess , enantioselective synthesis , stereocenter , enantiomer , chiral auxiliary , nucleophilic substitution , medicinal chemistry , ketone , nucleophile , lithium aluminium hydride , stereochemistry , organic chemistry , catalysis
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 α‐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 ⩾ 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 ⩾ 96%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)