Amino acids derivatives, synthesis

Tijhuis, M.W., J.D.M. Herscheid, and H.C.J. Ottenheijm A Practical Synthesis of N-Hydroxy-a-amino Acid Derivatives. Synthesis 1980, 890. 

SCHEME 31.32. The a- and (3-amino acid derivatives synthesis through an asymmetric hydrogen transfer. 

SCHEME 31.34. Radical addition of fluoro alkyl chain followed by enantioselective proton transfer chiral fluoro amino acid derivative synthesis. 

Oxidation of pollutants catalyzed by metallophthalocyanins 97ACR470. Recent developments in the use of A-phthaloyl-amino acid derivatives in synthesis 98SL457. 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

Like the Strecker synthesis, the Ugi reaction also involves a nucleophilic addition to an imine as the crucial step in which the stereogenic center of an a-amino acid derivative is formed4. The Ugi reaction, also denoted as a four-component condensation (A), is related to the older Passerini reaction5 (B) in an analogous fashion as the Strecker synthesis is to cyanohydrin formation. In both the Ugi and the Passerini reaction, an isocyanide takes the role of cyanide. 

This method was extended to the diastereoselective synthesis of amino acid derivatives from the 1,4-addition of chiral nonracemic azaenolates derived from optically active imines to enones90. 

The main application of the enzymatic hydrolysis of the amide bond is the en-antioselective synthesis of amino acids [4,97]. Acylases (EC 3.5.1.n) catalyze the hydrolysis of the N-acyl groups of a broad range of amino acid derivatives. They accept several acyl groups (acetyl, chloroacetyl, formyl, and carbamoyl) but they require a free a-carboxyl group. In general, acylases are selective for i-amino acids, but d-selective acylase have been reported. The kinetic resolution of amino acids by acylase-catalyzed hydrolysis is a well-established process [4]. The in situ racemization of the substrate in the presence of a racemase converts the process into a DKR. Alternatively, the remaining enantiomer of the N-acyl amino acid can be isolated and racemized via the formation of an oxazolone, as shown in Figure 6.34. 

In 1995, and regrettably missed in last year s review, Klotgen and Wiirthwein described the formation of the 4,5-dihydroazepine derivatives 2 by lithium induced cyclisation of the triene 1, followed by acylation <95TL7065>. This work has now been extended to the preparation of a number of l-acyl-2,3-dihydroazepines 4 from 3 <96T14801>. The formation of the intermediate anion and its subsequent cyclisation was followed by NMR spectroscopy and the stereochemistry of the final product elucidated by x-ray spectroscopy. The synthesis of optically active 2//-azepines 6 from amino acids has been described <96T10883>. The key step is the cyclisation of the amino acid derived alkene 5 with TFA. These azepines isomerise to the thermodynamically more stable 3//-azepines 7 in solution. 

Deming TJ (1998) Amino acid derived nickelacycles intermediates in nickel-mediated polypeptide synthesis. J Am Chem Soc 120 4240-4241... 

Another elegant example of a highly atom efficient process is the use of palladium-cataly.sed amidocarbonylation for the one-step synthesis of amino acid derivatives from an aldehyde, CO, and an amide (Eqn. (10)) (Beller et al., 1997, 1999). 

By using a mixture of ethyl acetate and D2O as solvent for hydrogenation, up to 75% deuterium is incorporated in the reduced product.13 This result indicates that the role of water here is not only as a solvent. Research on asymmetric hydrogenation in an aqueous medium is still actively being pursued. The method has been applied extensively in the synthesis of various amino acid derivatives.14... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

A new chiral auxiliary based on a camphor-derived 8-lactol has been developed for the stereoselective alkylation of glycine enolate in order to give enantiomerically pure a-amino acid derivatives. As a key step for the synthesis of this useful auxiliary has served the rc-selective hydroformylation of a homoallylic alcohol employing the rhodium(I)/XANTPHOS catalyst (Scheme 11) [56]. 

Weigele M, Bohacek R, Jacobsen VA, Macek K, Yang MG, Kawahata NH, Sundaramoorthi R, Wang Y, Takeuchi CS, Luke GP, Metcalf CA III, Shakespeare WC, Sawyer T. Synthesis of phosphono-containing amino acid derivatives and peptides as signal transduction inhibitors. PCT Int Appl W099/24442, 1999. 

W Kwapiszewski, J Kolwas. Synthesis of amino acid derivatives of benzocaine. III. Preparation of N-(N -N -dimethylaminoacyl)-benzocaines. Acta Polon Pharm 34 377-382, 1977. 

The molar ellipticity of these dendrimers was found to increase proportional to the number of chiral end groups. This is to be expected, in the absence of interactions between the terminal tryptophane moieties. No higher-generation dendrimers of this type have been reported. Other amino-acid-containing chiral dendrimers have been described by Meijer et al. who attached various amino acid derivatives to the periphery of poly(propylene imine) dendrimers (see Sect. 3) and more recently by Liskamp et al. (modification of polyamide dendra) [22] and Ritter et al. (synthesis of grafted polymerizable dendrimers containing L-aspartic acid components) [23]. 

Szymanska A, Wegner K, Lankiewitz L (2003) Synthesis of N-[(tert-Butoxy)carbonyl]-3-(9, 10-dihydro-9-oxoacridin-2-yl)-L-alanine, a new fluorescent amino acid derivative. Helv Chim Acta 86 3326-3331... 

The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives y-nitro-a-amino acids, which provides a convenient synthesis of side-chain modified a-amino acids (Eq. 4.114).152 Transformations of y-nitro-a-amino acid derivatives into a-amino acids occur by reductive denitration (see Section 7.2) into y-oxygenated a-amino acids by the Nef reaction (Eq. 

WIN 64821 (10) and (—)-ditryptophenaline (11) syntheses [7], not only effectively differentiated the two amide moieties but also most importantly marked the first in a series of stereochemical transfer steps in which the stereochemistry of the constituent L-amino acids was relayed to ultimately define each of the relative and absolute stereochemical configurations at all eight stereogenic centers found in the target compound. Finally, /V-methylation of the base-sensitive amide in 77 % yield using methyl iodide and potassium carbonate in acetone completed the 5-step synthesis of our key tetracyclic bromide monomer starting from commercially available amino acid derivatives. 

The application of olefin metathesis to the synthesis of piperidines continues to be widely employed. The use of ring closing metathesis (RCM) in the synthesis of fluorovinyl-containing a,P-unsaturated lactams 148 and cyclic amino acid derivatives 149 is shown below. A key improvement in these reactions is the addition of the Grubbs 2nd generation catalyst (G2) in small portions during the reaction to compensate for catalyst decomposition that occurs at elevated reaction temperatures <06EJOl 166>. 

General procedures for the synthesis of the imidazole core have been published in 2000. Solvent-free microwave assisted synthesis of 2,4,5-substituted imidazoles 64 from aldehydes 62 and 1,2-dicarbonyl compounds 63 in the presence of ammonium acetate and alumina has been reported <00TL5031>. V-protected a-amino glyoxals 65 were utilized as potential chiral educts for the synthesis of amino acid-derived imidazoles 66 <00TL1275>. 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

Fig.10. Gibson s synthesis of amino acid-derived polymers using a defined molybdenum initiator...

Perhaps the one major drawback with DIPAMP is the long synthetic sequence required for its preparation, though shorter and cheaper methods are now available [12]. The ligand continues to be a player for the synthesis of amino acid derivatives at scale, including L-Dopa, as mentioned above [12, 25, 27-29]. Its continued use is a testament to the power of the initial discoveries, as well as showing that a chemical catalyst can achieve selectivities only previously seen with enzymes. 

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