Amino acids from aldehydes

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

Strecker-cyanohydrin synthesis the synthesis of amino acids from aldehydes, HCN and NH3 in the presence of an aqueous fluid. 

Currently, most amino acids are obtained from natural resources and/or by fermentation. Amidocarbonylation is a viable alternative to the conventional Strecker reaction, which utilizes toxic hydrogen cyanide and anunonia to make aliphatic amino acids from aldehydes. 

Some appropriately heteroatom-substituted alkyl electrophiles undergo oxidative addition to Pd. For example, the carbonylative synthesis of a-amino acids from aldehydes and carboxamides shown in Scheme 5 must involve oxidative addition of 1 formed by the reaction of an aldehyde and a carboxamide to Pd to produce an a-amidoalkylpalla-dium species 2 as intermediate. It is likely that many other proximally heteroatom-substituted alkyl electrophiles will be found to undergo oxidative addition to Pd. 

HCN in Synthesis of Amino Acids from Aldehydes, Through Catalytic Amidocarhonylation of Syngas (CO/H2)... 

An efficient three-component coupling reaction for the synthesis of Af-acyl-a-amino acids from aldehydes, amides, and carbon monoxide, namely, amidocarbonylation, was first described by Wakamatsu in 1971.Recently, amidocarbonylation has successfully been catalyzed by palladium (Scheme The reaction would proceed as follows. 

Our first entry to the use of porphyrins as dipolarophiles in 1,3-DC reactions involved the reaction of porphyrins with azomethinic ylides, generated in situ from a-amino acids and aldehydes, to yield chlorins and isobacteriochlorins (bisadducts) <99CC1767, 05JOC2306>. 

The condensation of enantiomerically pure amino alcohols (derived from amino acids) with aldehydes to furnish 1,3-oxazolidines was studied by Kuhnert and Danks in 2001 (Scheme 6.212) [382], Under solvent-free conditions, microwave irradiation of equimolar mixtures of the amino alcohol and the aldehyde for less than 3 min provided high isolated yields of 1,3-oxazolidines with excellent diastereoselectivity. In the case of (-)-ephedrine, prolonged microwave irradiation (3 min) produced quantitative conversions and high diastereoselectivities. For shorter irradiation times (80 s) mixtures of the two diastereomers were obtained with moderate conversions. 

Aside from aldehydes, imines can be considered to be suitable substrates for the addition of reagents with umpoled carbonyl reactivity because useful building blocks and important compounds like a-amino acid and aldehydes will result from this conversion (Scheme 21). The S -configurated carbenoid 41 has been found to add to mesitylene-sulfonylimines 154, available from the corresponding aldehydes with predominant attack... 

Azomethine ylides can be generated in situ from various readily accessible starting materials. One of the easiest approaches to produce 1,3-dipoles involves the decarboxylation of immonium salts derived from condensation of a-amino acids with aldehydes or ketones [3, 204—206]. For example, the azomethine ylide 203, obtained by decarboxylating the condensation product of N-methylglycine and paraformaldehyde in refluxing toluene, reacts with Cjq to give the N-methyl-pyrrolidine derivative 204 in 41% yield (Scheme 4.32) [204]. 

Split synthesis of the library using four amino acids, four aldehydes, and five olefins in the presence of four mercaptoacyl chlorides (Scheme 3.110) generated the required proline library that was screened, after TEA cleavage of the products from the solid support, for inhibition of angiotensin converting enzyme ACE. 

Isatin has been used in the Strecker degradation of a-amino acids to aldehydes,434-437 and in the formation of benzaldehydes from benzyl-amines.431,435,438-440 These conversions have been the subject of a review, and mechanisms have been proposed.441 This formation of aldehydes from primary amines may, in part, explain some of the... 

One of the most valuable and widely used applications of C=N bond hydrogenation is in the field of reductive alkylation, in which an aldehyde or ketone is condensed with an amine and reduced in situ with an appropriate catalyst to give a substituted product. This very valuable reaction has most notably been employed for the racemic synthesis of amino acids from a-ketoesters and acids. This type of reduction can be very powerful, as illustrated by the synthesis of tetrahydro-b-carbolines 64 (76% yield) by the reductive coupling of 65 and 66 under conditions of 1 atm of hydrogen and palladium on carbon catalyst277. 

Ame Pictet (1857-1937) of the University of Geneva reported the formation of pyridine and isoquinoline bases from acid hydrolyzate of casein in the presence of formaldehyde in 1916 (8). Maillard ( ) claimed priority over him in discovering the condensation of amino acids with aldehydes or sugars to yield pyridine bases by citing his own paper (10). 

Two branches of the above reaction pathways provide active reagents for the degradation of a-amino acids to aldehydes and ketones of one less carbon atom (Strecker degradation), which is another arm of the Maillard reaction. Strecker aldehydes from these reactions are important flavor compounds (18). 

The capability of L-proline - as a simple amino acid from the chiral pool - to act like an enzyme has been shown by List, Lemer und Barbas III [4] for one of the most important organic asymmetric transformations, namely the catalytic aldol reaction [5]. In addition, all the above-mentioned requirements have been fulfilled. In the described experiments the conversion of acetone with an aldehyde resulted in the formation of the desired aldol products in satisfying to very good yields and with enantioselectivities of up to 96% ee (Scheme 1) [4], It is noteworthy that, in a similar manner to enzymatic conversions with aldolases of type I or II, a direct asymmetric aldol reaction was achieved when using L-proline as a catalyst. Accordingly the use of enol derivatives of the ketone component is not necessary, that is, ketones (acting as donors) can be used directly without previous modification [6]. So far, most of the asymmetric catalytic aldol reactions with synthetic catalysts require the utilization of enol derivatives [5]. The first direct catalytic asymmetric aldol reaction in the presence of a chiral heterobimetallic catalyst has recently been reported by the Shibasaki group [7]. 

Azomethine ylides are organic 1,3-dipoles possessing a carbanion next to an im-monium ion [ 12]. Cycloadditions to dipolarophiles provide access to pyrrolidine derivatives, useful intermediates in organic synthesis with stereo- and regiochem-ical control. Azomethine ylides can be readily produced upon decarboxylation of immonium salts derived from the condensation of a-amino acids with aldehydes or ketones. When they are added to C60, a fulleropyrrolidine monoadduct is formed in which a pyrrolidine ring is fused to the junction between two six-memberedrings of afullerene [13-15].Very importantly,functionalized aldehydes lead to the formation of 2-substituted fulleropyrrolidines, whereas reaction with AT-substituted glycines leads to AT-substituted fulleropyrrolidines (Scheme 1). 

The Strecker synthesis can form a large number of amino acids from appropriate aldehydes. The mechanism is shown next. First, the aldehyde reacts with ammonia to give an imine. The imine is a nitrogen analogue of a carbonyl group, and it is electrophilic when protonated. Attack of cyanide ion on the protonated imine gives the a-amino nitrile. This mechanism is similar to that for formation of a cyanohydrin (Section 18-14), except that in the Strecker synthesis cyanide ion attacks an imine rather than the aldehyde itself. 

Aldehydes related to common amino acids (3-methylbutanal from leucine, 2-methylpropanal from valine, phenylacetaldehyde from phenylalanine) are formed by enzymatic decarboxylation of the corresponding keto acids, which in turn are reversibly related to the amino acids by transamination [i.e., the keto acids are both degradation products of amino acids 147, 148) and intermediates in their synthesis 149). A third possibility—non-enzymatic oxidation of amino acids to aldehydes by enzymatically produced o-quinones—is established 150, 151) but is not discussed here. 

More unexpected was the formation of cyclopropane during the indium-mediated reaction of dibenzylidene acetone with allyl bromide which gave l,l-distyryl-2-(but-3-enyl)cyclopropane as a mixture of four isotopomers (Scheme 31) [158]. In a related reaction, a simple and efficient one-pot method was developed to give chiral homoallylic amines and amino acids from the respective aldehydes with high stereoselectivity [159]. 

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