title: Aldol additions of dihydroxyacetone phosphate to N-Cbz-amino aldehydes catalyzed by L-fuculose-1-phosphate aldolase in emulsion systems: inversion of stereoselectivity as a function of the acceptor aldehyde.
abstract: The potential of L-fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N-protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100 mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N-protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)-N-Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N-Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N-Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N-Cbz-glycinal and N-Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after C-C bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results.
authors.affiliation: Institute for Chemical & Environmental Research-CSIC, Jordi Girona 18-26, 08034-Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Espelt
authors.forename: Jordi
authors.initials: J
authors.lastname: Bujons
authors.forename: Teodor
authors.initials: T
authors.lastname: Parella
authors.forename: Jordi
authors.initials: J
authors.lastname: Calveras
authors.forename: Jesús
authors.initials: J
authors.lastname: Joglar
authors.forename: Antonio
authors.initials: A
authors.lastname: Delgado
authors.forename: Pere
authors.initials: P
authors.lastname: Clapés
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D003198:Computer Simulation; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000447:Aldehydes; D004655:Emulsions; D011108:Polymers; C024617:polyol; D004099:Dihydroxyacetone Phosphate; D000446:Aldehyde-Lyases; C036027:L-fuculosephosphate aldolase