title: A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5H)-furanones from (S)-ketone cyanohydrins.
abstract: (S)-Ketone cyanohydrins (S)-2 are accessible by enantioselective HCN addition to ketones 1 by using hydroxynitrile lyase from Manihot esculenta ((S)-MeHNL) as a biocatalyst. Acylation of (S)-2 gave the corresponding (S)-acyloxynitriles (S)-3, which can be cyclized by LHMDS to give 5,5-disubstituted (S)-4-amino-2(5H)-furanones (S)-4 and (S)-5. Different substituents (H. Me, OBn, OH) in the 3-position of the furanones were introduced by selecting the appropriate acylating agent, which in the case of benzyloxyacetyl chloride led to the novel structure type of 4-amino-3-hydroxyfuranones (S)-5. For the synthesis of 5,5-disubstituted (S)-tetronic acids (S)-8, ketone cyanohydrins (S)-2 were first transformed into the corresponding 2-hydroxy esters (S)-6. Acylation of (S)-6 gave 2-acyloxy esters (S)-7, which, by treatment with LHMDS or LDA, afforded tetronic acids (S)-8 in high yields and enantiomeric excesses. By debenzylation of benzyloxy acetoxy derivatives (S)-8e,f, the new vitamin C analogues (S)-9a,b were generated. All the described tetronic acid and aminofuranone derivatives were obtained in good chemical yields and without racemization with respect to the starting cyanohydrins (S)-2. In many cases the enantiomeric purity could be enriched by simple recrystallization (e.g. (S)-4a from 69% ee to > 99% ee).
authors.affiliation: Institut für Organische Chemie, Universität Stuttgart, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bühler
authors.forename: A
authors.initials: A
authors.lastname: Bayer
authors.forename: F
authors.initials: F
authors.lastname: Effenberger
mesh_terms: D000215:Acylation; D000446:Aldehyde-Lyases / Q000378:metabolism; D002384:Catalysis; D003460:Crystallization; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D002365:Manihot / Q000201:enzymology; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D005663:Furans; D009570:Nitriles; D000446:Aldehyde-Lyases; C079359:hydroxymandelonitrile lyase; C003422:tetronic acid