Cyclic derivatives of amino acids

Gas chromatography of amino acids has not really caught on, although for certain applications this option remains a viable alternative [118], 

Just as with hydroxy acids, hexafluoroacetone or dichlorotetrafluoroacetone converts amino acids to substituted oxazolidin-5-ones [119-122]. The mass spectra of these derivatives have been described [123]. 

Trifluorooxazolidinones are also produced by reacting amino acids with trifluoroacetic anhydride [124-126]. Cyclization was also achieved with 1,3-dicyclohexyl-carbodiimide (DCCI) [127]. The mass spectra of these compounds are also available [128]. 

---

Activated Cyclic Derivatives of Amino Acids in Peptide Synthesis J. C. Sheehan, Ann. N.Y. Acad. Sci., 1960, 88, 665-668. 

P. F. Butskus, Russ. Chem. Rev. (English Transl.) 31, 283 (1962). Cyclic derivatives of amino acids in peptide synthesis ... 

This section describes some derivatives of amino acids prepared by the condensation of a reagent with the amino group only or with both functional groups with the formation of a cyclic derivative. A number of reactions of this type have been tested for the derivatization of amino acids [191 ], mostly for a limited number. Some of the main reactions only will be mentioned here. 

Cooper G. and Cronin J. R. (1995) Einear and cyclic aliphatic carboxamides of the Murchison meteorite hydrolyzable derivatives of amino acids and other carboxylic acids. Geochim. Cosmochim. Acta 59, 1003-1015. 

Many heterocyclic compounds used as auxiliaries or catalysts have already been treated in preceding sections (e.g., alkaloids, derivatives of proline, cyclic derivatives of amino alcohols and hydroxy acids, etc.). This section deals with some special types of heterocyclic compounds which contain either only oxygen functions, or boron. 

Cyclic derivatives of phosphoric acid with chiral amino alcohols, e.g., 71, have been used as chiral electrophilic animation reagents (Section D.7.I.). As an example of such a compound, the reaction of (—)-ephedrine with phosphoryl chloride is given. 

Pentafluorobenzyl bromide has been used in the derivatization of mercaptans [55] and phenols [36], m the analysis of prostaglandins [37], and in quantitative GC-MS [5S] 1,3 Dichlorotetrafluoroacetone is used for the derivatization of amino acids to the corresponding cyclic oxazolidinones and allows the rapid analysis of all 20 protein ammo acids [d] Pentafluorophenyldialkylchlorosilane derivatives have facilitated the gas chromatographic analysis of a wide range of functionally substituted organic compounds, including steroids, alcohols, phenols, amines, carboxylic acids, and chlorohydrms [4]... 

Some other types of macrocycle compounds have been synthesized using adamantane and its derivatives. Recently, a new class of cyclobisamides has been synthesized using adamantane derivatives, which shows the general profiles of amino acid (serine or cystine)-ether composites. They were shown to be efficient ion transporters (especially for Na+ ions) in the model membranes [159]. Another interesting family of compounds to which adamantane derivatives have been introduced in order to obtain cyclic frameworks is crown ethers [160]. The outstanding feature of these adamantane-bearing crown ethers (which are also called diamond crowns ) is that ot-amino acids can be incorporated into the adamantano-crown backbone [160]. This family of... 

The analytical data obtained, particularly by the PUMA mass spectrometer on board Vega 1 during the flyby, indicate the presence of a large number of linear and cyclic carbon compounds, such as olefins, alkynes, imines, nitriles, aldehydes and carboxylic acids, but also heterocyclic compounds (pyridines, pyrroles, purines and pyrimidines) and some benzene derivatives no amino acids, alcohols or saturated hydrocarbons are, however, present (Kissel and Krueger, 1987 Krueger and Kissel, 1987). 

Natural products derived from amino acids form a broad and divergent group, including simple amino acid derivatives, alkaloids, and small, often cyclic, polypeptides. Simple amino acid derivatives, which are not uncommon in algae, are often oxidation or rearrangement products of one of the 20 common amino acids. Alkaloids and polypeptides are more complex in their structural modifications. 

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],... 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

A group at the Academy of Sciences in Moscow 197) has synthesized chiral threonine. Derivatives of cyclic imino acids form copper complexes with glacine and carbonyl compounds. Hydroxyethylation with acetaldehyde and decomposition of the resulting complexes produced threonine with an optical purity of up to 97-100% and with threo/allo ratios of up to 19 1 197). The chiral reagents could be recovered and re-used without loss of stereoselectivity. The mechanism of this asymmetric synthesis of amino acids via glacine Schiff base/metal complexes was also discussed 197). 

A number of syntheses of pyrrolizidine derivatives are based on cyclization of amino acids such as /3-(pyrrolidin-2-yl)propionic acid, 4-aminopimelic acid, and their homologues to give 3-oxo- and 3,5-dioxo-pyrrolizidines. Reduction of these cyclic amides leads to pyrrolizidines. 

The reaction of amino acid derivatives with epoxides has been explored to some extent in a recent study by Pascal.2082 Cyclic products are obtained, as shown in Eq. (036a). 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

The self-assembling cyclic D,L-cc-peptide nanotubes described demonstrate high stability on surfaces even after two months exposure to ambient temperature. NDI peptide nanotubes 18 may provide a facile method for the preparation of a new class of synthetic biomaterials [16b, 34a]. Recently Sanders and co-workers demonstrated the formation of amino acid-derived NDI hydrogen-bonded supramo-lecular organic M-helical nanotubes in nonpolar solvents and also in the solid state [34b]. The hydrogen-bonded supramolecular nature of the helical nanotubes was confirmed by the circular dichroism (CD) spectrum in chloroform with the addition of methanol, destruction of the supramolecular nanotubes was observed, due to the capabilities of such an aprotic solvent to compete for hydrogen-bond interactions [34b]. 

There are two important features of this overall approach. One is the convenient use of readily available, inexpensive starting materials, i.e., cyclic 1,3-dicarbonyl derivatives and amino acids. The other is the opportunity to introduce oxygen functionality into the (3-position on a pyrrole ring without having to resort to direct oxidation methods.100 By a simple conversion of the 3-acetoxy pyrrole functionality into pyrrole-3-triflate derivatives the door is opened for a wide variety of palladium-... 

Two functional groups in the molecule of amino acids offer the possibility of the formation of cyclic derivatives. On combining two molecules of the same amino acid, diketopiperazines are produced [264] (Scheme 5.25). With amido groups present in the... 

Other Oxazolidine as well as Thiazolidine Derivatives for Branching Amino Acids. The cyclic derivative of alanine and other amino acids employed most frequently for a-allq lation is not (1) but rather the benzaldehyde acetal (5), either with a benzoyl or with a Cbz group on nitrogen. These compounds were used for the preparation of 2-methyl-2-aminobutanoic acid, a-methylphenylalanine, a-methyllysine, 2-methylaspartic acid, and 2-methylglutamic acid. Bicyclic compounds containing oxazolidinone rings such as (6) (from alanine, leucine, and phenylalanine) and (7) (from azetidinecaiboxylic acid, proline, " hydroxyproline, and cysteine ) have also been applied to the synthesis of branched amino acids. 

In the list of amino acids which follows there are included all that have been obtained as products of protein hydrolysis and which are therefore necessary to consider in connection with the constitution of proteins. Most of them are derivatives of acids, which we have already studied though several of them contain cyclic or benzene groups derived from compounds which we shall take up in Part II. 

---