Enantiodivergent Chemoenzymatic Synthesis of 4‐Hydroxypiperidine Alkaloids
Abstract 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...
| Published in: | European Journal of Organic Chemistry |
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| Main Authors: | , , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2010
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1002/ejoc.201000837 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.201000837 https://onlinelibrary.wiley.com/doi/full/10.1002/ejoc.201000837 |
| Summary: | Abstract 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. |
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