A-Amino-p-hydroxycarboxylic acids

A suspension of Pd-C in ethyl acetate vigorously stirred under H2 until uptake of gas ceased, a soln. of /r 5-2-azidocyclohexanol and di- ert-butyl dicarbonate in the same solvent added, and the mixture stirred at room temp, under H2 for 19 h - product. Y 71%. Pre-saturation of the catalyst is important to prevent nitrile formation. F.e. incl. N-protected a-amino-p-hydroxycarboxylic acid esters and 2-acoxyamines, s. S. Saito et al.. Tetrahedron Letters 30, 837-8 (1989). 

Unfortunately, the position of the equilibrium does not favor synthesis, which requires to push the reaction by employing either an excess of the donor glycine (which is difficult to separate from the product) or the acceptor aldehyde (which at high concentrations may deactive the enzyme). A recently developed protocol relies on pulling of the equilibrium by (irreversible) decarboxylation of the formed a-amino-p-hydroxycarboxylic acid catalyzed by a decarboxylase to yield the corresponding aminoalcohols as final products [1452]. 

Optically active 3-amino-2-hydroxycarboxylic acid derivatives are often key components of medicinally important compounds. The synthesis of isopropyl (2i ,35)-3-amino-4-cyclo-hexyl-2-hydroxybutyrate (126) (Scheme 28) takes advantage of a [2 + 2]-cycloaddition reaction of the chiral imines 123, prepared from 63, to assemble the important diastereomeric azetidinone 124 as the crucial precursor for completion of this novel synthesis. Protection of the hydroxy group of 63 as either the TBS ether 119 or the tert-buty ether 120, followed by a DIBAL reduction at —78 °C, produces smoothly one of the aldehydes 121 or 122. Condensation of these aldehydes with either di-p-anisylmethylamine or benzylamine in the presence of anhydrous magnesium sulfate affords the four possible chiral imines 123a—d (Scheme 26). 

A way to anh-configurated a-amino-/ -hydroxycarboxylic acids is opened by the aldol addition of oxazolidine amides 7a and 7b. The method1061 is illustrated by a synthesis of (2R,3R)-p-hydroxyleucine (9) which is available from the major diastereomeric adduct 8 (d.r. 92 8) upon successive treatment with 1 N HC1 (30 min). 5 N HCl (100 C, 12 h), and propylene oxide (reflux in ethanol, 30 min). 

Alkyl oxazoline-5-carboxylates 71, precursors of P-amino-a-hydroxycarboxylic acids, have been produced by iodocyclisation of alkyl 3-benzamidocatboxylates 70. The oxazolines can be resolved enzymatically <99SL1727>. The amides 72 are cyclised to N-aryloxazolium salts 73 by fluoroboric acid <99EJ0297>. 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

Unlike ethylene glycol, a-hydroxycarboxylic acids, and p-mercaptoethanol, ligands such as ethanolamine, ethylenediamine, amino acids, and 2-aminoethanethiol do not form V2L2 complexes with vanadate [46], However, weakly formed products of VL stoichiometry (—546 ppm, —556 ppm) are observed with a number of a-amino acids [47], Because the amine functionality in amino acids is not suitable for formation of the cyclic [VN]2 core expected for a dimer, then one or the other of these VL compounds may correspond to the monomeric precursor to such a dimeric product. Certainly, with the a-hydroxycarboxylic acids, the monomeric complex can be a major component in solution. Similar VL complexes have not been reported for the amino alcohols. Perusal of the available reports suggests that the amine derivatives were studied under conditions where the nitrogen functionality was protonated, so the results may be somewhat misleading. 

The regioselective process P-amino-a-hydroxycarboxylic acid corresponding acrylic acid substn anthraquinone mediates enantiosele... 

In the mid-2000s, Griengl and coworkers reasoned that a small molecule with a similar pK as HCN, for example, nitromethane, could act as nucleophile for addition to carbonyl compounds (nitroaldol or Henry reaction Scheme 25.3) [111]. The Henry reaction is a classical name reaction in organic chemistry for the formation of C—C bonds. The resulting p-nitro alcohols can be transformed to nitroalkenes, 2-nitroketones, a-hydroxycarboxylic acids, and 1,2-amino alcohols. Although several other enzymes and proteins such as hydrolases and lipases [112], transglutaminase... 

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