P-hydroxy-a-amino acid derivatives

The group of Arai and Nishida investigated the catalytic asymmetric aldol reaction between tert-butyl diazoacetate and various aldehydes under phase-transfer conditions with chiral quaternary ammonium chloride 4c as a catalyst. The reactions were found to proceed smoothly in toluene, even at —40°C, when using 50% RbOH aqueous solution as a base, giving rise to the desired aldol adducts 23 with good enantioselectivities. The resulting 23 can be stereoselectively transformed into the corresponding syn- or anti-P-hydroxy-a-amino acid derivatives (Scheme 2.20) [42],... 

The gold(I) complex is prepared in situ by the reaction of (1) with bis(cyclohexyl isocyanide)gold(I) tetrafluoroborate (2), typically in anhydrous dichloromethane. The dihydrooxazolines obtained provide a ready access to enantiomerically pure p-hydroxy-a-amino acid derivatives. High diastereo- and enantios-electivity are generally maintained with a wide variety of substituted aldehydes, and a-isocyanoacetate esters. N,N-Dimethyl-a-isocyanoacetamides and a-keto esters have been substituted for the a-isocyanoacetate ester and aldehyde component, respectively, sometimes with improved stereoselectivity. The effect of both the central and planar chirality of (1) on the diastereo- and enantioselectivity of the gold(I)-catalyzed aldol reaction has been studied. The modification of the terminal di-alkylamino group of (1) can lead to improvements in the stereos-... 

They applied the intermediary oxocarbenium to a direct aldol type reaction of azlactones [78] via their oxazole tautomer and obtained the corresponding products with excellent enantio and diastereoselectivities (Scheme 3.35) [79]. The method enables efficient access to biologically and pharmaceutically intriguing p hydroxy a amino acid derivatives having a quaternary stereogenic center at the a carbon atom. 

Evans, D.A., Janey, J.M., Magomedov, N. and Tedrow, J.S. (2001) Chiral salen-aluminum complexes as catalysts for enantioselective aldol reactions of aldehydes and 5-alkoxyoxazoles an efficient approach to the asymmetric synthesis of syn and anti P-hydroxy-a-amino acid derivatives. Angewandte Chemie - International Edition, 40, 1884—1888. 

The Zr-BINOL catalyst system provides an efficient synthetic method of anti-p-hydroxy-a-amino acid derivatives (23) using glycine-derived silyl enolates (22)... 

P-Elimination Reactions of P-Hydroxy-a-amino Acid Derivatives. .. 267... 

Chart 2. Possible reactions between 0-Aryl sulfonates of P-Hydroxy-a-amino acid derivatives and bases or nucleophiles... 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

Scheme 10 p-Elimination of (S-Hydroxy-a-amino Acid Derivatives 961... 

Serine hydroxymethyltransferase is a PLP-dependent aldolase. It catalyzes interconversion between glycine and various P-hydroxy-a-amino acids, such as serine and threonine, via formation of a quinoid intermediate derived from PLP with the amino acid substrate (Scheme 2.9). This aldolase-type reaction is of interest as an asymmetric synthesis of a-amino acids via C-C bond formation. 

In the case of P-hydroxy-a-amino acids, oxazohdinone derivatives are formed with retention of configuration. 

A chelate derived from glycine is a source of yyn-P-hydroxy-a-amino acids. Most intriguingly, kinetic and thermodynamic conditions lead to different stereoisomers. 

Another approach to the synthesis of p hydroxy-a-amino acids is by aldol reaction of imines derived from amino adds. The benzophenone imine of glycine (7.102) undergoes highly enantioselective aldol addition with a range of aliphatic aldehydes, including (7.71) xmder phase-transfer conditions in the presence of the bromide salt of phase-transfer catalyst (7.103). A similar transformation is catalysed, in low to moderate ee, by the bimetallic catalysts developed by Shibasaki and CO workers. ... 

Kolasa, T. An Effective Synthesis of a,P-Dehydro-a-amino Acid Derivatives from N-Acyl-N-hydroxy-a-amino Acid. Synthesis 1983, 539. 

Scheme 13. Chain extension of a similar tartaric acid-derived L-threose compoimd 63, led to the P-hydroxy-a-amino acid, polyoxamic acid 64 (Scheme 17), and the same strategy led to the 5-amino-5-deoxy-L-taluronoside 65 from...

Willis et al reported an enantioselective direct aldol reaction for the synthesis of protected aryl P-hydroxy-a-amino acids catalyzed by chiral Mg (I I) complexes (Scheme 4.12) [12]. A catalyst system composed of 10 mol% of Mg(Cl04)2,11 mol% of (S,S)-Ph-Pybox (35), and diisopropylethylamine generated an enolate of a chiral glycine equivalent derived from isothiocyanate-substituted oxazolidinone (33). The... 

The a,p-double bond in amino acid derivatives and peptides represents, in addition to the amino and carboxy groups, the introduction of a third highly reactive function into the molecule. It is therefore pertinent in a discussion of the a,P-dehydroamino acids to devote some attention to their primary addition products, such as derivatives of a-mercapto- and a-hydroxy-a-amino acids. Further topics relevant in this context are their relationship to P-hydroxy- and P-mercapto-a-amino acid derivatives (elimination-addition sequence), as well as syntheses and reactions of pyruvoylamino acids, which result from the hydrolysis of dehydropeptides and can possibly serve as precursors of the latter by condensation with amino acid amides. On the other hand, p,y- and y S-dehydroamino acids will be excluded from the scope of this discussion. The isolated double bonds of these compounds undergo the normal olefin reactions and display no unusual characteristics. 

Okawa, K., T. Kinutani, and K. Sakai Studies on Hydroxy Amino Acids. I. A New Synthesis of Aziridine Derivative from P-Hydroxy-a-Amino Acid. Bull. Chem. Soc. Jap. 41, 1353 (1968). 

Some chiral phase-transfer catalysts can also promote enantioselective aldol and Mannich condensations of glycine imine donors with aldehyde and imine acceptors. These reactions provide important tools for the asymmetric constmction of P-hydroxy-a-amino acid and a,p-diamino acid derivatives, which are extremely interesting chiral units in the synthesis of pharmaceutical and natural products. For... 

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