Alanine derivative

There are few examples of [5 + 1] cyclizations from pyrimidine intermediates. Two of these involve the chloropropionic ester (194), which gives the 5,6,7,8-tetrahydro-7-one (195) with ammonia (59JCS1849), and the cyclization of a 4-ethynylpyrimidine-5-carboxylate with ammonia to give a pyrido[4,3-. In a recent patent, 5-ethoxycarbonylpyrimidin-4-yl-j8 -alanine derivatives are cyclized with ammonia to pipemidic acid analogues (80GEP2903850). One-carbon pyrimidine [5 +1] syntheses are included in Section 2.15.5.5.1 above. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Potential Energy Surfaces (Glycine and Alanine Derivatives). J. Am. Chem. Soc. 113, 6256-6265. 

Perczel, A., J. G. Angyan, M. Kajtar, W. Viviani, J.-L. Rivail, J.-F. Marcoccia, and I. G. Csizmadia. 1991a. Peptides Models. 1. Topology of Selected Peptide Conformational Potential Energy Surfaces (Glycine and Alanine Derivatives), J. Am. Chem. Soc. 113, 6256-6265. 

Fig. 24.8) [122]. Whilst this protocol can be used to prepare 3-pyridyl-alanine derivatives [22], the corresponding 2-pyridyl-alanine cannot be made [122]. However, Adamczyk has prepared several 2-pyridyl-alanine analogues through hydrogenation of the pyridine-N-oxide substrates in 80-83% ee (see Fig. 24.8) [123]. In general, only when the 2- and 6-positions of the pyridine ring are occupied can 2-, 3- or 4-pyridyl-alanine derivatives be prepared, without nitrogen modification, via hydrogenation with [phospholane-Rh]+ catalysts [122-124].

R Lygo, J. Crosby, J. A Peterson, Enantioselective Alkylation of Alanine-Derived Imines Using Quaternary Ammonium Catalysts , Tetrahedron Lett. 1999, 40, 8671-8674. 

The neutral alkali metal salts of benzohydroxamic acids have been found to undergo an unprecedented rearrangement to A(,A( -diarylureas. 2 side reaction, producing /9-alanine derivatives by way of a Lossen rearrangement, has been observed to accompany the hydrolysis of alkyl succinimidyl carbonates in basic aqueous buffers (see Scheme 97). The development of a modified Lossen rearrangement, whereby... 

Chirality derived from the readily accessible a-amino acids has been incorporated into the side chains of aza and diaza macrocyclic polyethers. A number of procedures suitable for peptide synthesis have proved (178) to be unsuitable for acylating the relatively unreactive secondary amine groups of aza crown ethers. Eventually, it was discovered that mixed anhydrides of diphenylphos-phinic acid and alkoxycarbonyl-L-alanine derivatives do yield amides, which can be reduced to the corresponding amines, e.g., l-172. By contrast, the corresponding bisamides of diaza-15-crown-S derivatives could not be reduced and so an alternative approach, involving the use of chiral A-chloroacetamido alcohols derived from a-amino acids, has been employed (178) in the synthesis of chiral receptors, such as ll-173 to ll-175, based on this constitution. 

Figure 2-1. Titration of a solution of alanine with a strong base. One equivalent of base is the amount needed to titrate the protons from one group on all the alanine molecules present in the solution. Below the titration curve is a calculation of the pi for alanine derived as the mean of its two pK values.

In the heterocyclic series, racemic 3-(fur-2-yl)alanine has been prepared from furfural using this approach. In addition, (3-(pyrid-3-yl)alanine, ° p-(quinol-3-yl)alanine, ° a p-(benzofuranyl)alanine derivative, 2-amino-3-(2,2 -bipyridi-nyl)propanoic acid, and some interesting derivatives of histidines—in particular 1-alkylhistidines with amphiphilic properties have all been synthesized using this methodology. The complete reaction sequence starting from an aldehyde and an A-acylamino acid derivative is shown in Scheme 7.150. 

Scheme 55 Synthesis of an Epimeric Mixture of C-Galactosyl Alanine Derivatives 4571 OAc...

Optically pure or almost pure a-methyl a-amino acids (alanine derivatives) can be prepared by reacting 5-substituted 2,5-dihydro-3,6-dimethoxy-2-methylpyrazines 1, which are derived from alanine and various amino acids as the chiral auxiliary, with alkylating agents, followed by hydrolysis (see Table 2). 

Table 2. a-Substituted a-Amino Propanoates (Alanine Derivatives) by Alkylation of 5-Substituted 2,5-Di-hydro-3,6-dimethoxy-2-mcthylpyrazines, Followed by Hydrolysis... 

The co-polymerization of D-alanine-derived A-propargylamide 22, L-valine-derived 23, and pyrene-based monomer 24 gives helical poly(22 -< o-23-c -24) carrying pyrene. The secondary structure of the co-polymer is tunable by the composition of the optically active amino acid units and solvent, which makes it possible to control the direction of the pyrene groups in the side chain. The interaction between the pyrene groups is small when the co-polymer takes a helical structure. The pyrene groups are regularly positioned in the polymer side chain. The co-polymer emits weak... 

Alanine-derived optically active A-propargylamide 22 and azobenzene-containing monomer 25 afford a co-polymer forming a helix. The azobenzene moiety isomerizes from trans-ioxm to cis-ioxm upon UV light irradiation, accompanying transition from helix to random coil. Then upon irradiation of visible light, the m-azobenezene moiety re-isomerizes into trans, while the polymer main chain keeps a random structure. This is presumably due to large steric repulsion around the azobenzene moiety to disturb recovery of a helical structure. 

Arsonoalanine was not a substrate or inhibitor of aspartate aminotransferase under the conditions tested (88), but it inactivated it progressively. Many alanine derivatives in which there is a good leaving group on C-3 do this (95-97), both to this enzyme and other pyridoxal enzymes (96), with some interesting results, e.g., the difference in reac-... 

Support-bound alkenes substituted with at least one electron-withdrawing group can react with primary or secondary amines (Table 10.6). If acrylates are used as Michael acceptors, the products (fl-alanine derivatives) are generally stable and do not undergo [l-elimination either upon N-acylation or upon treatment with TFA (for a longer synthetic sequence with a support-bound 2-(l-piperazinyl)propionate, see [42]). Suitable solvents for the addition of amines to electron-poor alkenes are THF, NMP, and DMSO. DMF is less suitable because it often contains dimethylamine, which also adds to Michael acceptors [112],... 

The quaternization of tertiary amines on cross-linked polystyrene has been investigated in detail. The most commonly used substrates in these studies have been N,N-dialkyl- 3-alanine derivatives because, after their quaternization, pure tertiary amines can be released from the support by treatment with a base (see Section 3.7). 

You have a peptide that is a potent inhibitor of nerve conduction and you wish to obtain its primary sequence. Amino acid analysis reveals the composition to be Ala(5) Lys Phe. Reaction of the intact peptide with FDNB releases free DNP-alanine on acid hydrolysis. e-DNP-lysine (but not a-DNP-lysine) is also found. Tryptic digestion gives a tripeptide (composition Lys, Ala (2)) and a tetrapeptide (composition Ala(3), Phe). Chymotryptic digestion of the intact peptide releases a hexapeptide and free alanine. Derive the peptide sequence. 

Schiff base complexes such as N-salicylideneglycinatoaquacopper(II) will also react with alkyl halides under basic conditions giving the alanine derivative (with Mel) and phenylalanine with benzyl bromide.441... 

---