Aminoacids hydroxy

N-protected aminoacids 14 behave as carboxyl partners in Ag20 promoted reactions of 2-bromo-isobutyramides or -propanamides affording, respectively, esters of 2-hydroxy-isobutyramides (ref. 20a) or lactamides 15 (ref. 20b). While we plan further research on stereochemical and other aspects of these reactions, model units obtained from 2-bromo-isobutyramides have been used in conformational studies of depsi-peptides (ref. 21). 

Silk fibroin contains no cystine and the content of lysine and histidine is also low (about 1% in total), but it does contain tyrosine phenolic (13%) and serine alcoholic (16%) sidechains. Since glycine accounts for 44% of the total aminoacid content, an N-terminal glycine residue is reasonably representative of most of the primary amino dyeing sites in silk fibres. Amino acid analysis of hydrolysed reactive-dyed silk indicates that the reaction between fibroin and reactive dyes takes place mainly at the e-amino group of lysine, the imino group of histidine and the N-terminal amino group of the peptide chain. In an alkaline medium, the hydroxy groups of tyrosine and serine also react [114]. 

The a-halogenated carboxylic adds, of which the simplest is chloro-acetic acid, are widely used in synthesis. Their conversion into hydroxy-acids (by hydrolytic elimination of the halogen) and into aminoacids (p. 275) may be mentioned here ... 

Aminoacid amides are suitable synthons for transformation to 3-hydroxy-thiadiazoles 25 (1967JOC2823, 1984WOP8402525) in moderate yields (Scheme 14). Clycinamide gave 4-chloro-l,2,5-thiadiazol-3-ol (1993JPP05140133) in a reaction with sulfur monochloride. 

CS133 Imperato, F. N-P-coumarylglutamic acid, an unusual hydroxy cinnamic acid-aminoacid derivative from black CS143 tea. Chem Ind (London) 1980 388. 

Ligand exchange has proved to be very successful in the separation of several enantiomers. Davankov and Rogozhin (41) used chiral copper complexes bonded to silica. The enantiomeric separation is based essentially on the formation of diastereomeric mixed complexes with different thermodynamic stabilities. It is generally accepted that chiral discrimination proceeds via the substitution of one ligand in the coordination sphere of the metal ion. Ligand exchange technique is especially effective for the enantiomeric resolution of aminoacids, aminoacids derivatives, and hydroxy acids (42). 

Isatoic anhydride can be used as a versatile synthon for the synthesis of a diverse set of molecules. The isatoic anhydride can be reacted with amines, amides, hydrazides, isothiocyanates, diketo substrates, aminoacids, amino-, thio or hydroxy anilines, as well as in a three-component reaction with aldehydes and amines to form a large set of diverse pharmacophores. 

The rules of Baldwin (55) for ring closure in trigonal systems (see p. 171 for an introduction) are the following 3- to 7-Exo-Trig processes (152-156) are all favored processes. 3- to 5-Endo-Trig (157-159) are disfavored but 6- and 7-Endo-Triq (160-161) are favored. The literature is replete with examples of 3- to 7-Exo-Trig for instance, lactonization of u-hydroxy-acids and esters are of this type, the formation of lactams from w-aminoacids and also the Dieckmann cyclization of diesters. 

Although it is reported that the U-5C-4CR can work well with nucleophiles other than methanol, such as primary or secondary amines, the only examples reported in the literature are those where trifunctional a-aminoacids such as lysine [67] or homoserine [66] or bifunctional aldehydes such as glycolaldehyde [65] are employed. In these cases, the side-chain amino or hydroxy group acts as the nucleophile and opens the cyclic intermediate generating the corresponding lactams or lactones. A less nucleophilic solvent such as trifluoroethanol is usually employed, in order to maximize the intramolecular attack. The observed stereoselectivities are, apart from a few examples [66], usually not very high this could be due to different factors (a) the side chains of the a-amino acids are not very bulky (b) the intramolecular nucleophilic attack could be faster than the methanol attack and the cyclic intermediate could not equilibrate to the thermodynamically favored isomer (c) the intramolecular nucleophilic attack on the more stable diastereoiso-meric cyclic intermediate could be kinetically less favored. 

A recent example of zeolite-catalyzed esterification involving biochemicals is the reaction of aminoacids with methanol. For instance, L-phenylalanine was converted to its methyl ester over H-USY at 130°C. However, the chiral carbon atom was racemized to a considerable extent, yielding an eventual ee of 52% (27). In the reaction of a, (3-unsaturated acids with phenols, the esterification over H-Beta is followed by an alkylation of the aromatic ring for instance resorcinol and acrylic acid react to form 7-hydroxy-3,4-dihydrocoumarin (28). 

Schraml et al.(137) found that the Si resonances of a series of silyl ester, alkoxy-silyl, and amino-silyl derivatives appear in different regions of the spectrum. On the basis of this information they suggested that Si NMR can be used for the structure elucidation of silylated hydroxy- or aminoacids. The silicon chemical shifts for DL-serine [55] and DL-threonine [56 ] are shown in ppm. The variation in the shielding for the alkoxy-silyl group demonstrates the previously noted sensitivity of Si NMR to the nature of R in Mc3SiOR. (140)... 

The aminohomologation of (/ )-24 via nitronate 53 can use the addition of 2-lithiofuran instead of 2-lithiothiazole. The furyl moiety can then be oxidized to the corresponding 2-aminoaldonic acids [67b]. Alternatively, the nucleophilic addition of alkoxy-methyllithium derivatives to nitrones of type 53 are either syn or anti selective in the absence or the presence of Et2AlCl, respectively. The adducts thus obtained were converted into C-4 building blocks and (3-hydroxy-a-aminoacids [67c]. 

Cordova and co-workers have studied the double aldol reaction of benzyloxyacetaldehyde using various a-aminoacids as catalysts. With L-proline and hydroxy-L-proline a tetrose and the L-allose derivative 33 were obtained in 41 and 28% yield, respectively, and with an enantiomeric excess higher than 98% (O Scheme 26). As expected, with D-proline as catalyst, the corresponding D-allose derivative was obtained with the same ease in a one-pot operation [151]. 

It is interesting to note that in fermented products the same alcohols always form, even if different sources of nitrogen, but not singular aminoacids, are available. Ketoacids can also be directly reduced to hydroxyacids such as lactic, 2-hydroxy-3-methyl butyric, 2-hydroxy-3-methyl pentanoic, 2-hydroxy-4-methyl pentanoic, 2-hydroxy-3-phenyl propionic and 2-hydroxy glutaric acids. The corresponding ethyl esters can dramatically influence the wine aroma. 

IR spectra of the La(III) and Ce(III) complexes of Schiff bases from the condensation of 2-hydroxy-1-naphthaldehyde with a-aminoacids show ONO-tridentate coordination (except for the L-glutamine derivative, which is OONO-tetradentate.479 The IR spectra of Pr(III), Eu(III), Gd(III), Dy(III) and Yb(III) complexes of furohydroxamic acid show that the ligands are N.O-bidentate.480 Raman and IR spectra of [Er(pic)4]", where Hpic = picolinic acid, reveal that the complex is 8-coordinate, with each ligand coordinated through a (unidentate) carboxylate O and a ring N atom.481... 

The reactions of enolates bearing chiral auxiliaries with formaldehyde or symmetrical ketones can be stereoselective. After removal of the auxiliary, nonra-cemic primary or tertiary alcohols are obtained. The reaction of lithium enolates of Schollkopfs lactim ethers 1.114 with symmetrical carbonyl compounds are highly stereoselective, as are the reactions of enolates of Seebach s imidazolidinone S.39 (R = Ph). In both cases, the enolate reacts from its least hindered face [154, 261] (Figure 6.11). After acidic hydrolysis, P-hydroxy-a-aminoacids are obtained with a high enantiomeric excess. However, when R = H, some unwanted epimerization can take place. 

Belokon and coworkers used the copper or nickel complex of the inline generated from 1.109 (R = H, Ph) and glycine as a chiral reagent [261, 384, 1276]. When reactions with this reagent are carried out at room temperature in the presence of MeONa, -(lS J-p-hydroxy-a-aminoacids are selectively obtained from MeCHO or aromatic aldehydes. When they are run in the presence of E N, a high selectivity for the (l, 2,S)-isomer is only obtained with MeCHO (Figure 6.85). 

A new cyclic heptapeptide cupolamide A (55) was isolated from two samples of the sponge Theonella cupola collected in Indonesia and Okinawa [49]. Three of the aminoacid residues, fram,-4-hydroxyproline, homoarginine and 2,4-diaminobutanoic acid are of uncommon occurrence in particular the hydroxy-proline is a constituent of collagen and occasionally has been found in terrestrial biota [50] and in marine... 

Callipeltins A-C are a new class of cyclic depsipeptides isolated from Callipelta sp. [137,138], Callipeltin A (125) appears very intriguing because of some structural features such as the presence of four new aminoacid residues, not previously isolated from natural sources (P-MeO-Tyr, N-Me-Gln, di-Me-Glu and 4-amino-7-guanidino-2,3-dihydroxy-eptanoic acid), the N-terminus blocked with a 3-hydroxy acid residue and... 

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