3-Amino esters synthesis

Lynn DM, Langer R (2000) Degradable poly(-amino esters) synthesis, characterization, and self-assembly with plasmid DNA. J Am Chem Soc 122 10761-10768... 

A novel ot-amino-ester synthesis consisted of the reduction of a-hydrazono- (a-azo-) esters, resulting from additions of benzenedia-... 

Duggan PJ, Johnston M, March TL. Enantioselective synthesis of a-fluoro- 33-amino esters synthesis of enantiopure, orthogonally protected a-fluoro- p3-lysine. 7. Org. Chem. 2010 75 7365-7372. 

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

The main reaction of this type has been the reductive cyclization of nitropyridine derivatives carrying an o-amino ester or o-aminocarbonyl substituent. These cyclize in situ via the o-diamino derivative to give pyridopyrazines of known constitution, either for establishment of structure of products obtained in the ambiguous Isay synthesis (see Section 2.15.15.6.1), or in the synthesis of aza analogues of biologically active molecules. 

Pyrimidine-5-carboxylic acid, 4-amino-2-methyl-ethyl ester synthesis, 3, 111... 

Thiophene-2,3-dicarboxylic acid, 4-amino-dimethyl ester synthesis, 4, 924... 

HONZL RUDINGER Peptide Synthesis Peptide synthesis by coupling ot acyl azides with amino esters... 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

The most widely used method for the laboratory synthesis of a-amino acids is a modification of the malonic ester synthesis (Section 21.7). The key reagent is diethyl acetamidomalonate, a derivative of malonic ester that aheady has the critical nitrogen substituent in place at the a-caibon atom. The side chain is introduced by alkylating diethyl acetamidomalonate in the same way as diethyl malonate itself is alkylated. 

Carboxylic acid, 161, also serves as starting material for a substituted pyrazine that has proven to be an important diuretic agent. As the first step in the synthesis the acid is converted to the corresponding amide (165). Treatment with a single equivalent of hypobromous acid effects Hoffmann rearrangement of only one of the amide groups. Ethanolysis of the intermediate carbamate leads directly to the amino ester (166). Exposure of the... 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

THE USE OF POLYSTYRYLSULFONYL CHLORIDE RESIN AS A SOLID SUPPORTED CONDENSATION REAGENT FOR THE FORMATION OF ESTERS SYNTHESIS OF N-[(9-FLUORENYLMETHOXY)CARBONYL]-L-ASPARTIC ACID a tert-BUTYL ESTER, P (2-ETHYL[(lE)-(4-NITROPHENYL)AZO] PHENYL]AMINO]ETHYL ESTER... 

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. 

Bazureau et al. have reported a similar protocol to that described in Sect. 8.1 for the rapid synthesis of 2-thioxo tetrahydropyrimidin-4-(lH)-ones via cycli-zation of a primary amine with an isothiocyanate and a /1-dielectrophile (Fig. 35) [138]. First a j6-amino ester was linked to the ionic hquid support... 

Recently, a very interesting preparation of P-peptides has been carried out by Kanerva and coworkers through a two-step lipase-catalyzed reactions in which N-acetylated P-amino esters were first activated as 2,2,2-trifluoroethyl esters with CALB [55]. The activated esters were then used to react with a P-aminoester in the presence of CALA in dry diethylether or diisopropylether (Scheme 7.31). In this peptide synthesis, the aminoester was used in excess and the unreacted counterpart was easily separated and later recyded. 

Carbenoid N-H insertion of amines with diazoacetates provides a useful means for the synthesis of ot-amino esters. Fe(III) porphyrins [64] and Fe(III/IV) corroles [65] are efficient catalysts for N-H carbenoid insertion of various aromatic and aliphatic amines using EDA as a carbene source (Scheme 16). The insertion reactions occur at room temperature and can be completed in short reaction times and with high product yields. It is performed in a one-pot fashion without the need for slow... 

Much more important than these reactions, however, are the reactions of CDI and its analogues with carboxylic acids, leading to AAacylazoles, from which (by acyl transfer) esters, amides, peptides, hydrazides, hydroxamic acids, as well as anhydrides and various C-acylation products may be obtained. The potential of these and other reactions will be shown in the following chapters. In most of these reactions it is not necessary to isolate the intermediate AAacylazoles. Instead, in the normal procedure the appropriate nucleophile reactant (an alcohol in the ester synthesis, or an amino acid in the peptide synthesis) is added to a solution of an AAacylimidazole, formed by reaction of a carboxylic acid with CDI. Thus, CDI and its analogues offer an especially convenient vehicle for activation of... 

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