title: Highly efficient aldol additions of DHA and DHAP to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate and L-fuculose-1-phosphate aldolases in aqueous borate buffer.
abstract: Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70-90%) were achieved with excellent (>98 : 2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz-amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields.
authors: Dept Biological Chemistry and Molecular Modeling, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain.
authors: Xavier
authors: X
authors: Garrabou
authors: Jordi
authors: J
authors: Calveras
authors: Jesús
authors: J
authors: Joglar
authors: Teodor
authors: T
authors: Parella
authors: Jordi
authors: J
authors: Bujons
authors: Pere
authors: P
authors: Clapés
mesh_terms: D000446:Aldehyde-Lyases / Q000378:metabolism*; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D001881:Borates / Q000737:chemistry; D002021:Buffers; D004098:Dihydroxyacetone / Q000737:chemistry / Q000378:metabolism*; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D000447:Aldehydes; D001881:Borates; D002021:Buffers; D014867:Water; D004099:Dihydroxyacetone Phosphate; D000446:Aldehyde-Lyases; C036027:L-fuculosephosphate aldolase; C022526:rhamnulose-1-phosphate adolase; D004098:Dihydroxyacetone