Formation of CC Bonds: Sections 14.1 ‐ 14.6

Abstract

The aldol reaction is one of the most powerful methods for carbon-carbon bond formation, and its catalytic asymmetric variants have great potential in contemporary organic synthesis ['I. Aldolases are enzymes which catalyze reversible and irreversible asymmetric aldol condensations in r~ature[~-~], via one of two distinct reaction mechanisms 1 ' 1 . Type I aldolases activate the donor/nucleophilic substrate via Schiff base formation with an active-site lysine residue. These enzymes are predominantly found in animals and higher plants, and do not require metal cofactors. Type I1 aldolases activate both donor and acceptor substrates via chelation to an active-site Zn", and are found mainly in microorganisms. Aldolases can be conveniently classified into groups according to their natural donor substrates, i. e. dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenol pyruvate (PEP), glycine, acetaldehyde, and a small number of other molecules. The ability of aldolases to accept a variety of unnatural acceptor substrates, and to generate new stereocenters of known absolute and relative stereochemistry reliably, has made them powerful tools for asymmetric synthesis.FDP aldolase catalyzes the reversible aldol addition reaction of DHAP and Dglyceraldehyde 3-phosphate (D-G~Y 3-P) to form D-FDP (Fig. 14.1-1). The equilibrium constant for this reaction has a value of -lo4 M-' in favor of FDP formation. The enzyme has been isolated from a variety of eukaryotic and prokaryotic sources, both in type I and type I1 forms [7-211. Generally, the type I FDP aldolases exist as tetramers (M. W. -160 KDa), while the type I1 enzymes are dimers (M. W. -80 KDa). For the