Amino stereoselective synthesis

Chiral 4,5-disubstituted oxazolidin-2-ones in stereoselective synthesis of (3-hydroxy-a-amino acids 97G475. 

Jackson and coworkers have used a new approach to the synthesis of fi-hydtoxy-ct-amino acids using farylthio nitrooxiranes. c-Jsopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of fi,Y-dihydroxyamino acids fScheme 4.6. The key step is stereoselective nucleophilic epoxlda-donof the Tarylthio-Tnltroalkene. Sy)i and ruin epoxides are selecdvely obtained by appropriate choice of epoxidadon reagent." ... 

The stereoselective synthesis ofruin -fi-amino-ct-hydroxy acid derivadves using nucleophilic epoxidadon of Tarydthio-Tnitroalkenes has been reported fEq. 4.411." ... 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Despite the lability of the N — O bond, addition of organomctallic reagents to 5-substituted isoxa-zolines provides a potential route for stereoselective synthesis of substituted 3-amino alcohols1. 

Table 1. Stereoselective Synthesis of a-Hydrogcnamino Acids Using 5-Amino-2,2-dimethyl-4-phenyl-1,3-dioxane as the Auxiliary51 53...

Stereoselective Strecker reactions with galactosylamine 1 can also be achieved with sodium cyanide and acetic acid in 2-propanol. The reactions, however, proceed slowly and with a lower stereoselectivity, giving diastereomeric ratios of the products between 3 1 and 7 1. The scope of the method can be extended to other glycosylamines, e.g., 2,3,4-tri-O-pivaloyl-a-D-arabinosyl-amine which allows the stereoselective synthesis of (A )-amino nitriles61,62. 

Ishihara K., Hattori K., Yamamoto H. Highly Stereoselective Synthesis of p-Amino Esters via Donhle Stereodifferentiation in EnantioseL Synth. fi-Amino Acids 1997 159, Ed. Juaristi E., Pb. Wiley-VCH N.Y. 

Figure 10.12 Stereoselective synthesis ofthe amino acid portion of nikkomycin antibiotics and hexulosonic acids using KDPGIc aldolase.

Recent Developments in the Stereoselective Synthesis of a-Amino Acids," Duthaler. R.Q. Tetrahedron, 1994, 50, 1539... 

The stereoselective synthesis of awri-P-amino-a-hydroxy acid derivatives using nucleophilic epoxidation of 1-arytlthio-l-nitroalkenes has been reported (Eq. 4.41).54... 

Syed, J., Forster, S. and Effenberger, F. (1998) Application of the Blaise reaction stereoselective synthesis of (4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates from (R)-cyanohydrins. Tetrahedron Asymmetry, 9, 805-815. 

A highly stereoselective synthesis of the (3-substituted P-amino sulfone 271 involves the addition of a sulfonyl anion, derived from A-PMB sultam 268 upon treatment with NaHMDS, to chiral A-sulfinyl imine (5)-269 <06OL789>. Removal of the A-sulfinyl followed by basic workup affords amine 271. The stereochemical outcome of the adduct 270 was established via proton NMR analysis of the Mosher s amide derived from 271. 

The reaction of lithiated 2-(l-chloroethyl)-2-oxazolines (367) with nitrones led to the stereoselective synthesis of oxazolinyl-[1.2] oxazetidines (372a,b) which are important as precursors of o.-hydroxy-j3-amino acids (Scheme 2.160) (601). 

Undheim [24] described the stereoselective synthesis of cyclic 1-amino-l-carboxylic acid using ruthenium-catalyzed enyne metathesis. His plan is shown... 

There is little doubt that the hydrogenation of dehydro a-amino acids is the best-studied enantioselective catalytic reaction. This was initiated by the successful development of the L-dopa process by Knowles (see below) and for many years, acetylated aminocinnamic acid derivatives were the model substrates to test most newly developed ligands. As can be seen below, this is the transformation most often used for the stereoselective synthesis of a variety of pharma and... 

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

While this example of the Robinson annulation is clearly not enantioselec-tive, the same antibody converts the mero-ketone [120] into the Wieland-Miescher (WM) decalenedione product kcM = 0.086 min-1 and Km = 2.34 mM at 25°C, parameters that give an impressive ER of 3.6 x 106. Good evidence suggests that the mechanism of the reaction involves the formation of a ketimine with the e-amino group of a buried lysine residue in the antibody, as shown in Fig. 39. Most significantly, the reaction delivers the ( )-(+)-WM product in 96% ee (by polarimetry) and in 95% ee by nmr and hplc analysis for a 100 mg scale reaction. A recent report tells that this antibody is to be made commercially available at a cost of 100 for 10 mg. The realization of that objective would mark the start of a new era of application of abzymes to organic stereoselective synthesis. 

In Section 5.03.6.2, a stereoselective synthesis of L-homophenylalanine from the racemic AAacetylated amino acid is described. The authors, however, found that substrate solubility limited the utility of this procedure. Having found an L-N-carbamoylase in Bacillus kaustophilus, they introduced the gene for this enzyme together with that for the N-acyl amino acid racemase from D. radiodurans into E. coli for coexpression. These cells, permeabilized with 0.5% toluene, were able to deliver L-homophenylalanine in 99% yield and were able to be used for multiple reaction cycles. 

Various cis-ot,g-epoxycarbonyl compounds are stereoselectively prepared via g-bromo-g-hydroxycarbony1 compounds by application of this Sn(ll) mediated aldol reaction to a-bromocarbonyl compounds (22). Also this reaction is employed for the stereoselective synthesis of 2-amino-2-deoxy-D-arabinitol. 

Since the migrating group retains its configuration, the use of enantiomerically enriched oximes provides a direct entry to enantiomerically pure lactams. These lactams may be used as a key building block for the synthesis of diverse compounds. Westermann and Gedrath applied this strategy to the stereoselective synthesis of enantiomerically pure o-.a-disubstituted a-amino acids (equation 135), bicyclic lactams and the spirocyclic framework of Histrionicotoxins (equation 136). 

A highly stereoselective synthesis of p-amino-ot-hydroxy acids from 3-benzoyl-amino carboxylates 115 has been developed by Cardillo and co-workers. 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

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