Amino acid derivatives double bonds

This compound removes a proton from the carboxylic acid, producing a cation that is readily attacked by the carboxylate nucleophile across one of the C-N double bonds - the protonated imine behaves as a good electrophile (see Section 7.7.1). The product is now an activated ester (an O-acylisourea) that can be attacked by any available nucleophile. The amino group of the second amino acid derivative provides the nucleophile, resulting in expulsion of a very stable urea as the leaving group, and production of the... 

Catalytic hydrogenation of the exocychc double bond of several oxazolones 611, in the presence of acetic acid, gives a-acylamino alcohols 613 via the saturated derivatives 612 (Scheme 7.196). Selected examples of amino acid derivatives and amino alcohols available from reduction of unsaturated oxazolones are shown in Table 7.45 (Fig. 7.56). 

It is noteworthy that stereoselectivities were high, even with sterically demanding substituents at the double bond. Similarly, the treatment of the cyclic bis (allyl) titanium complexes 18 with the imino esters 23a-c afforded the corresponding B-syn-configured cyclic unsaturated amino acid derivatives -25 and the Z-syn-configured isomers Z-25 with >98% regioselectivity and >98% diaste-reoselectivity in good yields. 

Addition Reaction. The double bond of dehydroalanine and e-methyl dehydroalanine formed by the e-elimination reaction (Equation 6) is very reactive with nucleophiles in the solution. These may be added nucleophiles such as sulfite (44). sulfide (42), cysteine and other sulfhydryl compounds (20,47), amines such as a-N-acetyl lysine (47 ) or ammonia (48). Or the nucleophiles may be contributed by the side chains of amino acid residues, such as lysine, cysteine, histidine or tryptophan, in the protein undergoing reaction in alkaline solution. Some of these reactions are shown in Figure 1. Friedman (38) has postulated a number of additional compounds, including stereo-isomers for those shown in Figure 1, as well as those compounds formed from the reaction of B-methyldehydroalanine (from 6 elimination of threonine). He has also suggested a systematic nomenclature for these new amino acid derivatives (38). As pointed out by Friedman the stereochemistry can be complicated because of the number of asymmetric carbon atoms (two to three depending on derivative) possible. 

Conformational analysis of the ctr-tetrahydroazoninone 12, performed using MM2 method, revealed two pairs of major confomers with a comparable energy, which differs by position of NH group against double bond <20050BC97>. The results obtained for this model structure were further used in the conformational analysis of azoninone amino acid derivatives (Section 14.10.4.3). 

Changing the transition-metal from palladium to rhodium (equation 62) makes possible, in addition to the straight-chain alkylation product (243), the regio- and stereoselective synthesis of amino acid derivatives with a terminal double bond (242), starting from optically active branched allylic substrates 241 (Table 21)" . Remarkably, the substitution products were obtained with high enantiomeric excesses, what might result from a slow isomerization of the intermediary formed allyl rhodium complexes ". 

BINAP-Ru-catalyzed hydrogenation of /3-substituted ( )-/3-(acylamino)acrylates gives /3-amino acid derivatives with a high e.e. (Eq. 2.3) [33]. The Z double-bond isomers that have an intramolecular hydrogen bond between amide and ester groups are more reactive, but are hydrogenated with a poor enantioselectivity. 

With chiral ligands the Heck reaction can be enantioselective. The amino-acid-derived phosphine ligand in the margin controls the Heck reaction of phenyl triflate with dihydrofuran. The ligand selects one enantiotopic face of the alkene (see Chapter 45 if you have forgotten this term) and the usual double bond migration and (5 elimination complete the reaction. 

Scheme 45. Peptides containing the IZD heterocyclic pTyr mimetics were synthesised in 10-11 linear steps from readily available starting materials such as 5-chloro-isothiazol-3-one 169, synthesised according to Method C, and amino acid derivatives 170. The key synthetic reaction was a novel Suzuki coupling of chloroheterocycle 169 with 4-phenylalanineboronic acid 170 to afford the fully protected scaffold 171. The J -terminus of 171 was subsequently elaborated via peptide coupling and the dipeptide 172 was deprotected to give inhibitor 173. The 4,5 double bond of 172 was reduced, isomers were separated, and each of them was further elaborated to afford compoimds 174 (Scheme 45).

Addition of RLi to cinnamaldehyde oxime ethers gives allylic amines. Those containing a chirality center at the carbinyl site are subject to 1,4-asynunetric induction, therefore optically active a-amino acid derivatives are readily synthesized (upon cleavage of the double bond). ... 

The diene (2.32) undergoes selective hydrogenation of the enamide double bond to give an amino acid derivative (2.33) containing an alkene functionality. The most enantioselective catalyst for this reaction was found to be the cationic rhodium complex of DUPHOS (2.05), which afforded less than 1% of the fully hydrogenated product as a by-product. 

Products synthesized in this way could be elaborated into amino-acid derivatives by oxidative cleavage of the double bond. 

The molecule, because of its simplicity and relative ease of synthesis lends itself to further development. For example, the disodium or dipotassium salt is an obvious candidate, as is saturation of the only double bond. Addition on the acyl chain is also obvious and reduction of the carboxyl groups either together, or individually, is another alternative. The possibility of amino acid derivatives yide infra, oligopeptides) is intriguing. The almost auxin-like activity makes it an appropriate candidate for development. 

Figure 7. Postulated structures of crosslinked amino acids derived from interaction of protein functional groups (NH, NH2, OH, SH) with the double bond of dehydroalanine and methyl dehydroalanine side chains. Asymmetric centers are designated by asterisks.

Ammonia is sufficiently nucleophilic that addition to the double bond of a conjugated ester is possible, even in the presence of the acyl carbon. Similarly, amines undergo conjugate addition. In both cases, the product is a 3-aminopropan-oic acid derivative (a P-amino acid derivative). Both ammonia and amine nucleophiles will be discussed in this section. 

The formal synthesis of (lR,4i .,9aS)-quinolizidine 233A (2276) from the amino acid derivative (S)-2280 by Fliemstra, Ruges, and their colleagues began with an unusual double bond migration induced by the Hoveyda— Gmbbs catalyst (7) followed by cross-metathesis with allyltiimethylsilane... 

The amino acid-derived stabilized phosphonium ylides 418 undergo double bond isomerization and condensation with loss of ethanol to afford the azepinedione ylides 419 in low yields (Scheme 87 2001TL141). 

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