Amino acid derivatives, acyl

U.S. 5981450 (2000) Fabry et al. (Henkel) Monoglyceride (ether) sulfate amino acid derivatives (acyl gluamates, vegetable protein hydrolyzates, or vegetable protein fatty acid condensates) Mild detergent mixtures... 

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. 

Bis(oxazolinyl)pyridine-Ce(IV) triflate complex 78 catalyzed the enantioselective 1,3-DC of acyclic nitrones with a, 3-unsaturated 2-acyl imidazoles. For example, C-phenyl 7V-benzyl nitrone reacted with 77 in the presence of 78 to give the adduct 79 with excellent diastereo-and enantioselectivity. Isoxazolidine 79 was then converted into P -hydroxy-P-amino acid derivatives by hydrogenation of the N-0 bond in the presence of Pd(OH)2/C and cleavage of the 2-acyl imidazole with MeOTf in MeCN <06OL3351>. 

Clayden and co-workers reported the dearomatiztion of an electron-deficient pyridine ring via intramolecular cyclization of an enolate shown in the scheme above <06OL5325>. Generation of the amino acid derived enolate of 46, with simultaneous activation of the pyridine ring by IV-acylation, leads to a stereoselective transition state 47. The authors postulate that the stereoselectivity arises from the manner in which the bulky PMP (p-... 

The symmetrical anhydride is prepared using dicyclohexylcarbodiimide in dichloromethane, the urea and solvent are removed, and the anhydride is dissolved in dimethylformamide and added to the peptide-resin (see Section 2.5). The anhydride is a more selective acylating agent than the 0-acylisourea and, thus, gives cleaner reactions than do carbodiimides, but twice as much amino-acid derivative is required, so the method is wasteful. It avoids the acid-catalyzed cyclization of terminal glutaminyl to the pyroglutamate (see Section 6.16) and is particularly effective for acylating secondary amines (see Section 8.15). 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

Interesting cyano, polyoxyethylene, and O-acetyl functionalized N-acyl-amino acid derivatives can be obtained from functionalized olefins (Table 1). Diamidocarbonylation products may also be synthesized in moderate yields from terminal diolefins [13-15]. 

The female produced long range sex pheromone of Migdolus fryans is AT-[(2 S)-2-methylbutyl]-(2S)-2-methylbutyramide 185 [345]. The acyl part as well as the alkyl part may be derived from isoleucine. Interestingly, this amide is accompanied by the ethyl ester of N-formyl isoleucine, which is also known from the scarab beetle, Phyllophaga elenans [181]. This amino acid derivative proved to be not attractive for both species its biological significance remains to be clarified. 

The chiral distinction capability of cinchonan carbamate CSPs for underivatized amino acids has not been fully elucidated yet, in contrast to the large embodiment of A-acylated and A-arylated amino acid derivatives vide infra). However, it seems that chiral amino acids can be successfully resolved into enantiomers if the amino acid side chain R residue) contains a functionality that represents a strongly interactive binding site with the selector such as an extended aromatic ring system like in thyroxin (T4). 

This enzyme [EC 3.5.1.14] (also referred to as histozyme, hippuricase, benzamidase, dehydropeptidase II, amino-acylase I, and acylase I) catalyzes the hydrolysis of an A-acyl-L-amino acid to yield a fatty acid anion and an L-amino acid. The enzyme has a wide specificity for the amino acid derivative. It will also catalyze the hydrolysis of dehydropeptides. 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

The difficulties encountered in aminoacylation of such lipo-amino acid derivatives are similar to those of the N-alkylated amino acids (see Vol. E 22c, Sections 10.1.1 and 10.1.2), but may be even worse due to steric hindrance of the large alkyl chains. Similarly, acylation with such amino acids leads to poor yields by the use of even stronger acylating reagents, e.g. HBTU, BOP, and PyBroP, with a marked improvement by the use of the mixed anhydride method although long reaction times were required. 128 ... 

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