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A Flexible Approach to Azasugars: Asymmetric Total Syntheses of (+)‐Castanospermine, (+)‐7‐Deoxy‐6‐ epi ‐castanospermine, and (+)‐1‐ epi ‐Castanospermine
Author(s) -
Liu Gang,
Wu TianJun,
Ruan YuanPing,
Huang PeiQiang
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903490
Subject(s) - castanospermine , stereocenter , chemistry , enantioselective synthesis , synthon , diastereomer , stereochemistry , retrosynthetic analysis , combinatorial chemistry , total synthesis , organic chemistry , catalysis , enzyme
The asymmetric total synthesis of natural azasugars (+)‐castanospermine, (+)‐7‐deoxy‐6‐ epi ‐castanospermine, and synthetic (+)‐1‐ epi ‐castanospermine has been accomplished in nine to ten steps from a common chiral building block ( S )‐ 8 . The method features a powerful chiral relay strategy consisting of a highly diastereoselective vinylogous Mukaiyama‐type reaction with either chiral or achiral aldehydes (≥95 % de ; de =diastereomeric excess) and a diastereodivergent reduction of tetramic acids, which allows formation of three continuous stereogenic centers with high diastereoselectivities. The method also provides a flexible access to structural arrays of 5‐(α‐hydroxyalkyl)tetramic acids, such as 17/34 , and 5‐(α‐hydroxyalkyl)‐4‐hydroxyl‐2‐pyrrolidinones, such as 18 and 25/35 a . The method constitutes the first realization of the challenging chiral synthons A and D and thus of the conceptually attractive retrosynthetic analysis shown in Scheme 1 in a highly enantioselective manner.