Amino acids in enantioselective synthesis

Descriptive Passage and Interpretive Problems 25 Amino Acids in Enantioselective Synthesis 1171... 

Substituted hydantoin derivatives have been used as precursors for d- and L-amino acids in chemical synthesis. However, they are hydrolyzed enantioselectively by the enzymes named hydantoinases some act specifically on D-5-substituted hydantoins, and others on the L-isomers. N-Carbamoyl amino acids formed are also hydrolyzed enantiospecifically by N-carbamoyl amino acid amidohydrolases to produce d- or l-amino acids (Fig. 17-15). Since the Kanegafuchi Chemical Industry, Japan, commercialized an enzymatic procedure for the production of D-p-hydroxyphenylglycine, which is a building block for the semisynthetic P-lactam antibiotic amoxycillin, various processes for amino acid production by means of hydantoinases have been developed 131 133. ... 

Very strong uncharged polyaminophosphazene bases with good chemical and thermal stability, their pKa ranging from 24 to 47 in the absolute MeCN scale and relatively non-nucleophilic. Useful in alkylation of enolates, in enantioselective a-alkylation of amino acids, in Ullmann synthesis. 

T. C. Boge, G. I. Georg, The medicinal chemistry of / -amino acids paclitaxel as an illustrative example in Enantioselective Synthesis of /3-amino acids, E. Juaristi (Ed.), Wiley-VCH, New York, 1997. 

An important issue is the right choice of substrate 1 which functions as an anion precursor. Successful organocatalytic conversions have been reported with indanones and benzophenone imines of glycine derivatives. The latter compounds are, in particular, useful for the synthesis of optically active a-amino acids. Excellent enantioselectivity has been reported for these conversions. In the following text the main achievements in this field of asymmetric organocatalytic nucleophilic substitutions are summarized [1, 2], The related addition of the anions 2 to Michael-acceptors is covered by chapter 4. 

Konopelski, J. P. In Enantioselective Synthesis of -Amino Acids, Juaristi, E., Ed. Wiley New York, 1997, pp 249-259,... 

Hydroxyalkyt and Epoxyalky Acids. The reaction of aldehydes or ketones with dialkyl hydrogenphosphonate continues to be widely used for the synthesis of a-hydroxyalkylphosphonates ° and magnesium oxide has been reported to be an effective catalyst for the reaction. The reaction has been used in enantioselective synthesis. For example, in the preparation of chiral a, -dihydroxyphosphonic acids 171 and 172 (Scheme 14), with preferential formation of the jyn-isomer 171, and the statin analogue 2-amino-1-hydroxy-3-phenylpropylphosphonic acid (173) (Scheme 15). Catalytic asymmetric... 

Derivatives from fi-Lactams Update in Enantioselective Synthesis of p-Amino Acids, 2" edition, E. Juaristi, V. A. Soloshonok, Eds John Wiley Sons, Hohoken, NJ, 2005 Chp. 20, p477. 

Enantioselective synthesis of a-amino acids A practical and general route to a-amino acids involves enantioselective reduction of alkyl trichloromcthyl ketones with catccholboranc (CB) in the presence of the oxazaborolidine (S)-l (0.1 cquiv.) to give (R)-alcohols 2. The (R)-alcohols (2) arc converted on treatment with NaOH... 

Owing to the importance of optically active amino acid derivatives and the lack of successful systems for catalytic asymmetric CDC reactions of glycine derivatives with p-keto esters, Wang and co orkers embarked on the study of enantioselective CDC reactions of secondary and tertiary amines for the synthesis of optically active a-alkyl a-amino acids. In the presence of a catalytic amount of Cu(OTf)2 and BOX ligand L2 as the chiral catalyst, in combination with DDQ as the stoichiometric oxidant, the reactions of glycine esters 47 with a-substituted p-keto esters 48 underwent smoothly to afford the desired products 49 in satisfactory yields, moderate dr and excellent ee (Scheme 2.17). 

Podlech, J. In Enantioselective Synthesis of P-Amino Acids (2nd Edn.) John Wiley Sons Hoboken, NJ, 2005, pp 93-106. (Review). 

---