An efficient benchtop system for multigram-scale kinetic resolutions using aldolase antibodies

The preparative scale kinetic resolution of racemic aldols 1-4 using aldolase antibodies 38C2 (Aldrich no. 47995-0) and 84G3 (Aldrich no. 52785-8) is described. These reactions use a biphasic aqueous/organic solvent system that allows the catalyst to be reused. Reaction scales range from miligrams to grams, with 0.0086 to 0.12 mol% of antibody binding sites. Because antibodies 38C2 and 84G3 have opposite enantioselectivities, both aldol product enantiomers are accessible by kinetic resolution.     

Sets of aldolase antibodies with antipodal reactivities. Formal synthesis of epothilone E by large-scale antibody-catalyzed resolution of thiazole aldol

[formula: see text] Three monoclonal aldolase antibodies, generated against a beta-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions of ent-8a-k, providing optically pure 8a-k by kinetic resolution. Compounds (+/-)-8a, (+/-)-8g, and (+/-)-8k have been resolved in multigram quantities using 0.003, 0.005, and 0.0004 mol% antibody catalysts, respectively. Resolved compounds 8a-k are useful synthons for the construction of epothilones A-E (2-6) and their analogues. Here, a formal synthesis of epothilone E, 6 has been achieved starting from compound 8g.     

Chiral electromigration methods in food analysis

This review article addresses the different chiral capillary electrophoretic methods that are being used for the study and characterization of foods and food compounds (e.g., amino acids, organic acids, sugars, pesticides). An updated overview, including works published till December 2002, on the principal applications of enantioselective procedures together with their main advantages and drawbacks in food analysis is provided. Some anticipated applications of chiral electromigration methods in food characterization are also discussed.     

Direct organocatalytic asymmetric Mannich-type reactions in aqueous media: one-pot Mannich-allylation reactions

The first direct organocatalytic asymmetric Mannich-type reactions in aqueous media are demonstrated herein. l-Proline-catalyzed reactions in aqueous media to provide β-formyl substituted α-amino acid derivatives with excellent diastereoselectivities (dr up to 19:1, syn/anti) and high enantioselectivities (ee between 72 and >99%). These conditions provided for the development of novel one-pot asymmetric syntheses of cyclic γ-allyl substituted α-amino acid derivatives (ee up to >99%). This was accomplished by combining the proline-catalyzed Mannich-type reactions with indium promoted allylations in aqueous media.     

Water-compatible organocatalysts for direct asymmetric syn-aldol reactions of dihydroxyacetone and aldehydes

A novel organocatalyst was developed that effectively catalyzed the reactions of unprotected or protected dihydroxyacetone with a variety of aldehydes to provide syn-aldol products with good yields and ee values up to >99%. Significantly, this amide catalyst was effective with a variety of nonaromatic aldehyde acceptors that had proven difficult in the presence of other catalysts. Reactions of protected dihydroxyacetone proceeded in aqueous media without addition of organic solvents.     

Catalytic Enantioselective Retro-Aldol Reactions: Kinetic Resolution of β-Hydroxyketones with Aldolase Antibodies

High enantiomeric enrichment after 50% conversion : Racemates of aldols can be resolved by the title reaction [Eq.(1)] by use of the aldolase antibody 38C2 or 33F12; the ee values of the unconverted aldols are greater than 95% in most cases. Since the antibodies also catalyze the aldol reaction–that is, the reverse reaction–it is possible to prepare both enantiomers using the same antibody catalysts.     

Expanding the Potential of DNA for Binding and Catalysis: Highly Functionalized dUTP Derivatives That Are Substrates for Thermostable DNA Polymerases

The discovery of a simple structural motif allows for the enzymatic synthesis by polymerase chain reactions (PCR) of modified DNA (see reaction scheme) bearing side chains similar or even identical to those of several amino acids. Libraries of DNA functionalized with both cationic and anionic groups may now be readily prepared. R=I, HgCl; X=functional group.     

Proline-catalyzed one-step asymmetric synthesis of 5-hydroxy-(2E)-hexenal from acetaldehyde.

For the first time, the L-proline-catalyzed direct asymmetric self-aldolization of acetaldehyde is described affording (+)-(5S)-hydroxy-(2E)-hexenal 2 with ee's ranging from 57 to 90%. Further transformations of 2 into synthetically valuable building blocks are presented. A mechanism for the formation of 2 is proposed.