Stereocenter-recognition

The equilibrium of the reaction is predominantly on the product side and the specificity of substituent orientation at C-3 and C-4 (adjacent to the newly formed vicinal diol bond) is absolute - always threo (Scheme 2.185). However, if the a-carbon atom in the aldehyde component is chiral (C-5 in the product), only low chiral recognition of this remote stereocenter takes place. Consequently, if an a-substituted aldehyde is employed in racemic form, a pair of diastereomeric products will be obtained. 

Within group-I aldolases, FDP aldolase from rabbit muscle has been extensively used for the synthesis of biologically active sugar analogs on a preparative scale (Scheme 2.187). For example, nojirimycin and derivatives thereof, which have been shown to be potent anti-AIDS agents with no cytotoxicity, have been obtained by a chemoenzymatic approach using RAMA in the key step. As expected, the recognition of the a-hydroxy stereocenter in the acceptor aldehyde was low [1400, 1401]. 

A fascinating variant of the enzymatic cyanohydrin formation consists in the use of nitroalkanes (as nonnatural nucleophiles) instead of cyanide (Scheme 2.209) [1568,1569]. Overall, this constitutes a biocatalytic equivalent to the Henry-reaction producing vicinal nitro-alcohols, which are valuable precursors for amino alcohols. Using (5)-HNL, the asymmetric addition of nitromethane to benzaldehyde gave the nitroalcohol in 92% e.e., while for p-nitrobenzaldehyde the stereoselectivity dropped sharply. With nitroethane, two stereocenters are created Whereas the stereoselectivity for the alcoholic center was high (e.e. 95%), the recognition for the adjacent center bearing the nitro moiety was modest and other (dia)stereomers were formed in up to 8%. 

Figure 10.5 Recognition of stereocenters at various distances from reaction centers.

The resolution of racemic alcohols in which the hydroxyl residue is not at the stereogenic center is of particular interest and can be done through so-called remote resolutions [73]. The best results have been found when the stereocenter is in p-posi-tion with respect to the alcohol fxmction, while when moving the stereocenter to a further position the processes result in a loss of chiral recognition. In this context, Backvall and Deska have reported the KR of axially chiral primary allenic alcohols, which occurred with high enantioselectivities by using a crude preparation of porcine pancreatic lipase (PPL) in combination with five equivalents of vinyl butanoate using DIPE at room temperature (Table 9.2) [74]. In some cases a quaternary stereocenter contains a hydroxymethyl residue, and the remote resolution is achieved... 

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