A-Aminoacid synthesis

Fehrentz, J A, Castro, B, An efficient synthesis of optically active a-(t-butoxycarbonylamino)-aldehydes from a-aminoacids. Synthesis, 676-678, 1983. 

STRECKER Aminoacid synthesis Synthesis of a-amino acids from aldehydes or ketones via cyanohydnns... 

Free-radical reactions in the synthesis of diketopiperazines and other cyclic derivatives of a-aminoacids 97CRV53. 

This method is widely applicable to the unambiguous synthesis of quinoxalin-2-ones." It involves the intermediate preparation of a l,2,3,4-tetrahydro-2-oxoquinoxaline by the reductive ring closure of the o-nitrophenyl derivative of an a-aminoacid. These derivatives are formed readily from the aminoacid and an o-nitrohalogenobenzene. The final step of oxidation of the tetrahydro- to the dihydro-quinoxa-line is carried out with potassium permanganate or hydrogen peroxide. The preparation of 7-nitroquinoxalin-2-one illustrates the application of this synthesis ... 

Further, Wasserman and coworkers developed a direct acylation of stabilized phosphonium ylides by carboxylic acids in presence of the EDCI/DMAP (way c). This last method allows the introduction of a-aminoacid structures into the resulting P-oxo phosphorus ylides [19-25],opening the way to the total synthesis of depsipeptide elastase inhibitors [22,24] or cyclic peptidic protease inhibitor EurystatinA [20]. 

Aminoacid peptides (c.f. Z-/ -Ala-/ -Ala-OC2H5, 75% yield) have also been prepared by this pyrazolide method. 31 A glutathione synthesis was accomplished by the pyr-azolide method in the following way [32]... 

A-Thiazolyl a-amino acids 56 have been prepared. The preferred route to these compounds would utilise the Hantzsch synthesis, however in this case the in situ formation of the required thiourea derivatives of a-aminoacids 52 failed. A variety of isothiocyanate reagents were tried, with the result being either no reaction, decomposition or the corresponding thiohydantoin 53. A modified version of the Hantzsch synthesis was developed. If the bromoketone 54 is initially treated with sodium thiocyanate an a-thiocyanatoketone 55 is formed, subsequent addition of the amino acid ester 51 yields A-thiazolyl a-amino acids 56 <00T3161>. 

As the latter were not easily accessible by chemical synthesis at that time, new methods of preparing these ferrocene derivatives were developed and introduced in 1969. It was then proved that the U-4CRs of chiral a-ferrocenyl-alkylamines can form diastereomeric a-aminoacid derivatives stereo-selectively, and it was further shown that after the reaction the a-ferrocenyl groups of the products can be replaced by protons, thus resynthesizing the chiral a-ferrocenyl-alkylamines simultaneously." Later, the development of this ferrocene chemistry was given up since such syntheses cannot form the products in sufficient quantity and stereoselective purity. ... 

Swansonine and castanospermine synthesis starts with the a-aminoacid, y-semialadehyde and, via piperidine-6-carhoxyhc acid synthetases, L-pipecolic acid. This compound is a substrate to HSCoA and acetyl-CoA. As a result of this activity, the second ring is established. Subsequently, it changes to 1 -indolizidinone and, by oxidation reaction, produces castanospermine or swansonine (Figure 50). 

An extensive review of the chemistry of aliphatic and aromatic azides is given by Boyer and Canter [167] and Gray [168]. Organic azides are subject to various reactions such as the Bergmann degradation and the synthesis of peptides, the well known Curtius rearrangement, the Darapsky synthesis of a-aminoacids [169], for synthesis of triazoles [170], tetrazoles ( Schmidt reaction ) [169] and [171] etc. These reactions lie beyond the scope of the present book. 

Esters of a-aminoacids can be conveniently used as amine components in the Ugi reaction. In principle they could be used in the Ugi reaction as chiral auxiliaries since they are readily available in both enantiomeric forms and there is a number of literature procedures for their removal at the end of the synthesis. Moreover in several synthetic applications in the field of peptidomimetics their structure may also be retained. 

The presence of oe-hydroxycarboxylic acids together with a-aminoacids could lead to an estimate of the local concentration of ammonia when these molecules were synthesised. Such an estimation method implies the assumption that the syntheses of the two classes of molecules were simultaneous and started from the same organic substrate, i.e. aldehydes25 . From aldehydes, aminoacids can be obtained by the Strecker synthesis (aldehyde, HCN, NH3 in aqueous solution), while hydroxyacids can be synthesised from the cyanhydrin synthesis (aldehyde + HCN) followed by a hydrolysis. Nevertheless, it must be emphasised that all aminoacids detected in carbonaceous chondrites cannot be obtained by the Strecker synthesis. This remark limits the interest of the previous arguments concerning the concentration of NH3 during the accretion phase. 

From both a biochemical and a synthetical point of view the synthesis of hydrogenated uracils by direct reduction of the pyrimidine ring is a reaction of considerable importance. These reduced uracils bear a similar relationship to /3-aminoacids as the hydantoins do to a-aminoacids. A practical method of reducing uracil combinations, therefore, opens up a new method of synthesizing representatives of this important class of... 

Diazoketone building blocks, such as 181, were prepared by a multistep synthesis departing from appropriate tu-aminoacids. 

Alkenes undergo nucleophilic addition when coordinated to cationic fragments, for example, [Re(CO)5]+ or [ReCp(NO)(PPh3)]+, and electrophihc abstractions when coordinated to the more electron-rich ReCp(CO)2 fragment. One example is the formation of (76) from [Re(CO)s ( -C4H6)]+ and [Re(CO)5] , but many others are known including the synthesis of a-aminoacids with organometallic side chains. 

H. R. Kricheldorf, a-Aminoacid-N-carboxyanhydrides and Related Heterocycles Synthesis, Properties, Peptide Synthesis, Polymerization. Springer-Verlag, Berlin, 1987. 

EFFICIENT ASYMMETRIC SYNTHESIS OF N-tert-BUTOXYCARBONYL a-AMINOACIDS USING 4-tert-BUTOXYCARBONYL- 5,6-DIPHENYLMORPHOLIN-2-ONE (R)-(N-tert-BUTOXYCARBONYL)ALLYLGLYCINE... 

Kricheldorf, H., a-Aminoacid-N-Carboxy-anhydrides and Related Heterocycles - Synthesis Properties, Peptide Synthesis, Polymerization, Springer Berlin, (1987) p 3. Leuchs, H. Geiger, W., Ber. Dtsch. Chem. Ges, (1908) 41, 1721. 

Reduction of 2-acylamino acrylates to give aminoacids Hydrogenation with C2-Symmetrical BINAP Rh and Ru Complexes Asymmetric Hydrogenation of Carbonyl Groups Regioselective asymmetric hydrogenation ofenones Asymmetric reduction of ketones with kinetic resolution A Commercial Synthesis of Menthol... 

Olefins are very important industrial raw materials, and much effort has been devoted toward using them as substrates in asymmetric synthesis [811, 812, 853], The industrial synthesis of nonracemic a-aminoacids by catalytic hydrogenation was ore of the first important uses of olefins in asymmetric synthesis [859], Today, the Sharpless epoxidation of allylic alcohols [807, 808, 809] is one of the most popular methods in asymmetric synthesis. The importance of pyrethrinoid pesticides, bearing a cyclopropane skeleton, justifies the efforts devoted to the asymmetric synthesis of cyclopropanes from alkenes [811,812, 937],... 

---