With Keto Acids

To the best of our knowledge only one example of diastereoselective intramolecular Ugi reaction employing a ketoacid is known [80]. The condensation of acid 89 with (S)-l-phenylethylamine proved to be stereoselective, giving a mixture of the four possible diastereoisomers 90 in a 42 42 8 8 ratio, with the trans stereoisomers pre- 

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Treatment of this rare, autosomal recessive disorder involves a diet low in these amino acids as well as dietary supplementation with keto acids and thiamine. 

Starting with known butylated ketal-acid 85, readily synthesized in high yield directly from ketal-acid 32, deketalization as before with oxalic acid treated silica gel gave comparable results to before, with keto-acid 86 being produced in 85%... 

A series of dicarboxylic acids 73 were synthesized as a result of a systematic study of the condensation of isatin 7 with keto acids 72 in the presence of potassium hydroxide or sodium hydroxide (Table 1) [53-59],... 

Reductive amination was also conducted using cell extracts from E. coli strain SC16496 expressing PDHmod and cloned FDH from Pichia pastoris. Cells from a 15-L tank had 133 u/g FDH, 65u/g PDH (phenylpyruvate assay), and 12.7 u/g PDH (assayed with keto acid 3). The extract was used for conversion of 30g 3 to 4 in close to 100% yield, and this material, after filtration for protein removal, was converted to 2 by BOC protection. Further experiments showed that the E. coli extract could be used at 2.5% w/v concentration instead of the 12.5% concentration used for batches with Pichia pastoris extract. In subsequent experiments, the substrate input was increased to 100 g/ L and the reaction was carried out at pH 8.0. Cell extracts of E. coli strain SC16496 after polyethyleneamine treatment, clarification and concentration was used to complete the reaction in 30hrs with >96% yield and >99.9% ee of product 4. PDHmod and FDH expressed in E. coli have now been used to prepare several hundred kg of BOC-protected amino acid 2 to support the development of Saxagliptin (Hanson et al., 2007). 

The distribution of metabolites obtained after incubation of pineapple slices with keto acids and keto esters, potential precursors of the corresponding hydroxy compounds, is summarized in Table II. The metabolization steps comprise esterification, reduction to hydroxy compounds, formation of acetoxy esters, and cyclization to the corresponding lactones. Metabolization rate and distribution of formed products strongly depend on the structures of the precursors. The detection of these metabolites proves the enzymatic capability of pineapple tissue to catalyze these conversions, an aspect which might be interesting for future use of pineapple tissue cultures in the production of chiral compounds. 

Table 28 Condensation Reactions of 3,4-Dihydro-2//-pyrrole and 2,3,4,5-Tetrahydropyridine with -Keto Acid...

In the course of examining the chemistry of oxazolidines, Meyers developed diastereoselective alkylation reactions of fused, bicyclic lactams such as 91 (Scheme 3.15). The approach is particularly useful for the construction of a large array of molecules containing quaternary stereogenic centers [68]. The starting bicyclic lactams are readily prepared by condensation of chiral /3-amino alcohols such as 89 with keto acids 90 to give 91, which subsequently participates in diastereoselective alkylation reactions. Hydrolysis... 

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