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Enantiodivergent Chemoenzymatic Synthesis of 4‐Hydroxypiperidine Alkaloids
Author(s) -
Bartali Laura,
Casini Andrea,
Guarna Antonio,
Occhiato Ernesto G.,
Scarpi Dina
Publication year - 2010
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.201000837
Subject(s) - chemistry , kinetic resolution , stereoselectivity , enantiomer , candida antarctica , hydroboration , hydrolysis , organic chemistry , enantioselective synthesis , lipase , alcohol , yield (engineering) , catalysis , borane , stereochemistry , allylic rearrangement , derivative (finance) , enzyme , materials science , financial economics , economics , metallurgy
An efficient chemoenzymatic synthesis of both enantiomers of fagomine, as well as of cis and trans ‐4‐hydroxypipecolic acid is reported. The synthesis starts from commercial δ‐valerolactam which, after a Pd‐catalyzed methoxycarbonylation of the corresponding vinyl phosphate, is subjected to allylic oxidation to give a racemic 4‐hydroxytetrahydropyridine derivative in 57 % overall yield. This product is resolved by an enzyme‐catalyzed esterification using immobilized lipases from Candida antarctica (Novozym 435) and Burkholderia cepacia (lipase PS Amano IM). The latter provides the corresponding R esters and the S alcohol in 95 and 94 % ee , respectively. The S alcohol is then converted into L ‐fagomine by a stereoselective hydroboration/oxidation as key steps and the cis ‐(2 R ,4 S )‐4‐hydroxypipecolic acid by stereoselective hydrogenation. The corresponding D ‐fagomine and cis ‐(2 S ,4 R )‐4‐hydroxypipecolic acid, as well as trans ‐(2 R ,4 R )‐4‐hydroxypipecolic acid can be prepared by the same strategy after hydrolysis of the R ester obtained by kinetic resolution.