A-Amino-P-hydroxy acid

Reaction of Bisglycinatocopper(II). Bisglycinatocopper(II) [13479-54-4] condenses with ahphatic aldehydes. Removal of copper from the condensate results in P-hydroxy-a-amino acid. This is a classical synthetic method of DL-threonine, but the formation of i //o-isomer is unavoidable. 

Jackson and coworkers have used a new approach to the synthesis of P-hydroxy-a-amino acids using (arylthio)nitrooxiranes. D-Isopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of P,y-dihydroxyamino acids (Scheme 4.6). The key step is stereoselective nucleophilic epoxida-tion of the 1-arylthio-l-nitroalkene. Syn and anti epoxides are selectively obtained by appropriate choice of epoxidation reagent.51... 

O Donnell imine 23 with various aldehydes, giving P-hydroxy-a-amino acid esters 44 with high enantiomeric excess,1401 as shown in Scheme 15. 

M. Horikawa, J. Bush-Petersen, E. J. Corey, Enantioselective Synthesis of P-Hydroxy-a-amino Acid Esters by Adol Coupling Using a Chiral Quaternary Ammonium Salt as Catalyst , Tetrahedron Lett. 1999, 40, 3843-3846. 

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. 

The reaction scope was further developed with a range of aromatic and aliphatic aldehydes to furnish a range of p-hydroxy-a-amino acids, which are important constituents of many natural products (62). The resultant bicyclic adducts were obtained in good to excellent yield and represent differentially and orthagonally protected p-hydroxy-a-amino acids. The template removal was easily conducted by... 

Cyclization of P-Hydroxy-a-amino Acids with Sulfuryl Chloride Trt-Azy-OBzl Typical Procedure 61 ... 

Azlactone Formation from P-Hydroxy-a-amino Acids... 

LLB, LiOH, and H2O promoted the direct aldol reaction of glycinate Schiff bases 12 with aldehydes 3, providing access to p-hydroxy-a-amino acid esters 13 (Scheme 4,bottom) [7],... 

AW-Dimethyl-Ot-isocyanoacetamide 10 is the substrate of choice in the reaction with acetaldehyde (98.6% ee) or primary aldehydes such as propionaldehyde (96.3% ee) or isovaler-aldehyde (97.3% ee) (Scheme 8B1.5, Table 8B1.5) [19]. The oxazolinecarboxamides 11 thus prepared can be converted to P-hydroxy-a-amino acids by acidic hydrolysis. The aldol reaction... 

The phase-transfer-catalyzed enantioselective direct aldol reactions of glycine donor with aldehyde acceptors provide an ideal method for the simultaneous construction of the primary structure and stereochemical integrity of P-hydroxy-a-amino acids, which are extremely important chiral units. In the first report from the Miller s group, N-benzyldnchorudinium chloride (4a) was employed as a catalyst for the reaction of 1 with heptanal, and the corresponding aldol product 21 was obtained in 74% yield, though the diastereo- and enantioselectivities were unfortunately not satisfactory (Scheme 2.18) [40]. 

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],... 

Steinreiber J, Fesko K et al (2007) Synthesis of y-halogenated and long-chain P-hydroxy-a-amino acids and 2-amino-l,3-diols using threonine aldolases. Tetrahedron 63 8088-8093... 

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. 

Electrophilic amination is a general entry to chiral a-amino acids or functionalized P-amino and P-hydroxy a-amino acids with an anti stereochemistry. The chiral enolate technology has been applied for the obtaining of C-N bond-forming reactions with stereochemical control. 

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-... 

Makino, K., Goto, T., Hiroki, Y., Hamada, Y. Stereoselective synthesis of anti-P-hydroxy-a-amino acids through dynamic kinetic resolution. Angew. Chem., Int. Ed. Engl. 2004,43, 882-884. 

---