Alanine-derived amide

In this context, a wide variety of different chiral primary amines has been developed and tested in this reaction with different results (Scheme 2.8). The first example of a primary amine-catalyzed Michael reaction of ketones with nitroalkenes was reported by Cordova,who found that alanine-derived amide 20a was an excellent catalyst for this transformation. However, in this report, the reaction scope was also mainly focused on the use of cyclohexanone, with a single example of an acyclic enone (2-butanone) providing the Michael... 

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... 

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. 

Type I CSPs have also been used with aqueous mobile phases. Pirkle et al. (32) have reported on the resolution of N-(3,5-dinitrobenzoyl) derivatives of M-amino adds and 2-aminophosphonic adds on an (l )-N-(2-naphthyl)-alanine-derived CSP using a mobile phase composed of methanol-aqueous phosphate buffer. The utility of achiral alkyltrimethylammoruum ion-pairing reagents was also investigated. Other examples include the following (1) The recently commercialized ot-Burke 1 CSP resolves the enantiomers of a number of underivatized p-blockers using an ethanol-dichlorornethane-ammonium acetate mobile phase (33) (2) an (R)-l-naphthylethylurea CSP was used to resolve N-(3,5-dinitrobenzoyI)-substituted amino adds and 3,5-dinitrobenzoyl amide derivatives of ibuprofen, naproxen, and fenoprofen with acetonitrile-sodium acetate mobile phases (34). 

PIFA easily converts succinic acid derivatives (32) to -alanine derivatives (33). Limited use of PIFA (1 equiv.) allows the rearrangement of 3-cyclohexene-1-carboxamide (34) without oxidation of the double bond, as shown in Scheme 12. Cyclohexanone is obtained by the PIFA oxidation of 1-cyclohex-enecarboxamide (35). Selective oxidation of the primary amide (36) occurs without effect on secondary or tertiary amides in the same molecule. The rearrangement of the cyclopropane derivative (37) accompanies the ring cleavage to give the -alanine derivative (38) after treatment with benzyloxycarbonyl chloride. ... 

Amides of 2-iodoxybenzenesulfonic acid 495 were prepared by dioxirane oxidation of the corresponding 2-iodobenzenesulfamides 494 and isolated as stable, microcrystalline products (Scheme 2.141) [660], A single-crystal X-ray structural analysis of the alanine derivative 495 [R = (5)-CH(CH3)C02Me] showed a combination of intra- and intermolecular I--0 interactions leading to a unique tieptacoordinated iodine(V) center in this molecule [661], The analogous esters 497 were prepared similarly from the respective sulfonate esters 496 [662],... 

While the amide component of phosphoramidates appears to be centering on l-alanine derivatives, considerable variations in the aryl ester component are still reported. Simple phenyl esters may well be the most extensively employed substructure [130, 131], especially in nucleotide analogues of the general structure 62 [116,127,132-136]. However in cases such as the hydroxamic acid 63, an inhibitor of 6-phosphogluconate dehydrogenase for use in trypanosomiasis, addition of simple substituents such as methyl groups to the phenyl ring has resulted in more than a tenfold increase in potency [137]. In some cases, deployment of a naphthyl ester (e.g., 64) has accompanied preparation of the phenyl ester [116, 132, 133]. Other studies have focused on the naphthyl esters (Fig. 13) [138-141]. 

With N,0 mixed donor ligands several complexes have been reported with ligands such as 4,5-dichloro-2-cyano-3,6-dione-l,4-cyclohexen-l-ol,1445 isonicotinic acid,1446 p-aminobenzoic acid,1447 alanine, histidine or histamine derivatives,1448-1450 [N(0)C(CN)2]-,1451 pyridine-carboxylate derivatives, 1452 1454 [N(pph20)2] (263),1455 bis(sulfonyl)amide derivatives,1456,1457 tris(pyridyl)-... 

L-tryptophan is compulsory, the biosynthetic machinery displays wide latitude in its ability to condense a second auxiliary amino acid—L-alanine in the case of (+)-ll,ll -dideoxyverticillin A (1)—to afford a tryptophan-derived diketopiperazine intermediate 13. Mirroring Woodward and Robinson s biogenetic hypothesis for the calycanthaceous alkaloids, single-electron oxidation of the electron-rich tryptophan residue would likely initiate an oxidative dimerization of the diketopiperazine precursor with concomitant cyclization to yield the octacyclic intermediate 17. Subsequent A-methylation of the amides would then yield an unembellished skeletal core of the dimeric epipolythiodiketopiperazine alkaloids. The first step en route... 

Unusual amino acids include a class of unnatural a-amino acids such as phenylalanine, tyrosine, alanine, tryptophan, and glycine analogs, and f)-amino acid analogs containing 1,2,3,4-tetrahydroisoquinoline, tetraline, l,2,3,4-tetrahydro-2-carboline, cyclopentane, cyclohexane, cyclohexene, bicyclo[2.2.1]heptane or heptene skeletons. Different selectors were exploited for the separation of unusual amino acids, most of the production being made by Peter and coworkers teicoplanin [41, 56, 84, 90, 93, 124, 141-144], ristocetin A [33, 94, 145, 146], and TAG [56, 147]. Enantiomeric and diastereomeric separations of cyclic -substituted a-amino acids were reported by other authors on a teicoplanin CSP [88, 89], Ester and amide derivatives of tryptophan and phenylalanine were recently analyzed on a Me-TAG CSP [58],... 

The pyrimidine 46 was obtained from methyl /3-alaninate after cyclization with an isourea derivative (90T7803) and when the ester was transformed into the amide and Schiff base was cyclized with benzoic anhydride, the result was a racemic substituted perhydropyrimidin-4-one (91JOC2553). 

Robust peptide-derived approaches aim to identify a small drug-like molecule to mimic the peptide interactions. The primary peptide molecule is considered in these approaches as a tool compound to demonstrate that small molecules can compete with a given interaction. A variety of chemical, 3D structural and molecular modeling approaches are used to validate the essential 3D pharmacophore model which in turn is the basis for the design of the mimics. The chemical approaches include in addition to N- and C-terminal truncations a variety of positional scanning methods. Using alanine scans one can identify the key pharmacophore points D-amino-acid or proline scans allow stabilization of (i-turn structures cyclic scans bias the peptide or portions of the peptide in a particular conformation (a-helix, (i-turn and so on) other scans, like N-methyl-amino-acid scans and amide-bond-replacement (depsi-peptides) scans aim to improve the ADME properties." ... 

A hypothetical biosynthetic sequence has been proposed for the 3-alkyl-2,6-dimethylpyrazines (482) from various species of Odontomachus ants, as shown in Scheme 65. The acyloin (507), prepared by condensation of the pyruvate with active acetate, or the derived dione (508) may condense with the amide (509) of alanine, ultimately giving the 3-alkyl-2,6-dimethylpyrazines (482) (141). A separate biogenesis is envisaged for the 3-alkyl-2,5-dimethylpyrazines (481) such as 3-isopentyl-2,5-dimethyl (20h) and 2,5-dimethyl-3-styrylpyrazines (20j,... 

Differences of <5 = 0.32-0.40 in the, 9F chemical shift for epimeric A -acylated Mosher derivatives of aliphatic a-amino acids, in particular alanine, as well as its amides and peptide derivatives, are sufficiently large to serve as a racemisation test23. However, high-field spectrometers are recommended to provide improved sensitivity (<0.5%). Table 19, representing analysis data taken at 376.5 MHz, can be found in Section 3.2.2.9. Analysis of absolute configuration of amino acids and amines can be more accurate using a modified Mosher method24. 

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