BI Amino acids

Fig. 18. Crystal structure of 30, an amino acid bis-urea derivative. The urea groups are in a parallel orientation and form the expected bidentate hydrogen bonds...

The use of optically resolved PTC catalysts for the synthesis of enantiomerically pure compounds is no doubt an attractive field. Asymmetric PTC has become an important tool for both laboratory syntheses and industrial productions of enantiomerically enriched compounds. Recently, Lygo and coworkers [207-216] reported a new class of Cinchona alkaloid-derived quaternary ammonium PTC catalysts, which have been applied successfully in the enantioselective synthesis of a-amino acids, bis-a-amino acids, and bis-a-amino acid esters via alkylation [207-213] and in the asymmetric epoxidation of a/p-unsaturated ketones [214-216]. 

P. E. Smith and B. M. Pettitt. Amino acid side-chain populations in aqueous and saline solution Bis(penicillamine) enkephalin. Biopolymers, 32 1623-1629,... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Cram and his coworkers have pioneered the use of bis-binaphthyl crowns as chiral com-plexing agents for ammonium salts and amino acid salts. In these systems, the chiral binaphthyl unit provides a steric barrier within the macrocycle which allows discrimina-... 

The saturated 2,2 -bis-oxazolones (10) are conveniently prepared [Eq. (7)] in two-steps via iV, iV -diacylbis-(a-amino acids), which cyclize in hot acetic anhydride. If R is aliphatic, alkali hydroxides... 

Saturated 2,2 -bis-5-oxazolones (10) react with diamines under mild conditions to form polyamides (34) of high molecular weight in quantitative yield [Eq. (21)]. These polymers are composed of dicarboxylic acid, a-amino acid, and diamine units in a regular arrangement of both head-to-tail and tail-to-tail amide groups. They represent a cross between conventional polyamides and a-amino acid homopolymers. A feature of this polymerization is that no small molecules such as H2O, NHg, or CO2 are lost during reaction. 

Methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid Bis(Trimethylsilyl)acetamide 7-Aminocephalosporanic acid... 

The most effective catalysts for enantioselective amino acid synthesis are coordination complexes of rhodium(I) with 1,5-cyclooctadiene (COD) and a chiral diphosphine such as (JR,jR)-l,2-bis(o-anisylphenylphosphino)ethane, the so-called DiPAMP ligand. The complex owes its chirality to the presence of the trisubstituted phosphorus atoms (Section 9.12). 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

The second important group of configuralionally stable bis-protected a-amino aldehydes are the V-dibenzvl derivatives 5, easily prepared from amino acids in a three-step procedure65. These aldehydes react with various nucleophiles to normally provide the nonchelation-con-trolled adducts in high diastereoselectivity. This anti selectivity is observed when diethyl ether or telrahydrofuran is used as reaction solvent. Certain Lewis acidic nucleophiles or additives, such as tin(IV) chloride, in dichloromethane as solvent force chelation and therefore provide the. syn-adducts, once again with a high diastereoselectivity. 

V,/V-Bis(trimethylsilyl) alkyl glycinates can be deprotonated and then alkylated on carbon (4) to give homologous a-amino-acid derivatives ... 

Herbert and Hay reported a bisphenolic monomer, 3,8-bis(4-hydroxyphenyl)-A-phenyl-1,2-naphthalimide (Table 6.1), as well as its corresponding polyf V-phenyl imido aryl ether sulfone) via transimidization reactions with hydrazine monohydrate, aliphatic amines, and an amino acid.193 These polysulfones with... 

In the case of simple amino acids and dipeptides, esterification of the carboxyl groups occurs on heating in toluene with the appropriate bis(triorganotin) oxide or triorganotin hydroxide 481, 482), the water being removed azeotropically. 

The first reported method for the direct phosphonomethylation of amino acids used phosphorous acid and formaldehyde (7). Typically, aqueous solutions of the amino acid, phosphorous acid, and concentrated (coned) hydrochloric acid were heated to reflux with excess aqueous formaldehyde or paraformaldehyde. The reaction proceeded equally well with either primary or secondary amines. However, with primary amines such as glycine, the yield of glyphosate was usually quite low, even at reduced temperature, and 1 1 1 stoichiometry. The resulting glyphosate acid (GLYH3) reacted faster than glycine, so the bis-phosphonomethyl adduct 2 always predominated. With excess phosphorous acid and formaldehyde, good isolated yields of this 2 1 adduct 2 have been obtained (8). 

Other cyclizations at phosphorus have been observed when certain phosphinates were used in the acid-catalyzed Mannich reaction. As observed previously with various phosphonous acid derivatives, reaction of aliphatic phosphinic acids with primary amines favored the formation of 2 1 adducts (73). Thus, glycine and other a-amino acids reacted under the typical conditions with excess formaldehyde and alkyl phosphonous acids to give the bis-phosphinylmethyl adducts 125. 

In the first step, a resin-bound secondary amine is acylated with bromoacetic acid, in the presence of N,N-diisopropylcarbodiimide. Acylation of secondary amines is difficult, especially when coupHng an amino acid with a bulky side chain. The sub-monomer method, on the other hand, is facilitated by the use of bromoacetic acid, which is a very reactive acylating agent Activated bromoacetic acid is bis-reactive, in that it acylates by reacting with a nucleophile at the carbonyl carbon, or it can alkylate by reacting with a nucleophile at the neighboring ah-phatic carbon. Because acylation is approximately 1000 times faster than alkylation, acylation is exclusively observed. 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

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