Dehydro a-amino acids

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

There is little doubt that the hydrogenation of dehydro a-amino acids is the best-studied enantioselective catalytic reaction. This was initiated by the successful development of the L-dopa process by Knowles (see below) and for many years, acetylated aminocinnamic acid derivatives were the model substrates to test most newly developed ligands. As can be seen below, this is the transformation most often used for the stereoselective synthesis of a variety of pharma and... 

Recent results have shown that a number of other commercially available ligands can be expected to have industrial potential for the hydrogenation of dehydro a-amino acid derivatives. However, it must be pointed out that in most cases model substrates and not industrially relevant targets have been investigated until now. Chiral Quest has shown that Rh-TangPhos as well as Rh-f-Ke-talPhos (for structures, see Fig. 37.9) were able to hydrogenate a variety of a-de-hydro amino acid derivatives with ee-values of 98->99%, TONs of up to 10000... 

In contrast to dehydro a-amino acids, the hydrogenation of acetylated /1-dehy-droamino acid derivatives has only recently been of industrial interest and, accordingly, no applications on a larger scale have yet been reported. Several ligands such as certain phospholanes or phosphoramidites might have industrial potential, but until now these have only been tested on model substrates under standard conditions [50]. Chiral Quests TangPhos and Binapine (Fig. 37.10) have been shown to hydrogenate several acetylated dehydro / -amino acid derivatives with ee-values of 98-99% and TONs of 10000 at r.t., 1 bar [3, 47]. 

On the other hand, esters of dehydro a-amino acids dimerize at 145°C in the absence of solvent to give 44 after a [4 + 2]-cycIodimerization and... 

Transamination reactions have also been described for 4-(aminomethylene)-2-substituted-5(47T)-oxazolones. As an example, displacement of the A-methyl-heteroarylamino group of a 4-[(A-heteroaryl-A-methyl)aminomethylene]-2-phen-yl-5(47T)-oxazolone 420 by an a-amino acid derivative produces p-amino-a,(3-dehydro-a-amino acid precursors 421 (Scheme 7.137). ... 

A new approach to a,/3-dehydro-a-amino acids by reaction of aldehydes or acetals with... 

The first family is represented by peptides based on a, 3-dehydro a-amino adds in which a C=C bond confers rigidity and electronic Y-conjugation on the system (Section 11.1). Peptides rich in these amino acids are widespread in nature, particularly as antibiotics, and possess interesting conformational properties. 1-11 In addition to the E and Z configurational isomers, occurring when two different atoms (substituents) on CP are present, fully-extended, characteristically flat conformations or p-tums and 310/a-helices may be induced by u,p-dehydro a-amino acids. 

A large number of a, 3-didehydro-a-amino acids have been identified as constituents of relatively low molecular weight cyclic compounds from microbial sources. However, the presence of a,p-didehydroalanine in bacterial as well as in mammalian histidine ammonia lyase and in phenylalanine ammonia lyase shows that the occurrence of a,p-didehydro-a-amino acids is not limited to small molecules alone 8 These residues are incorporated in natural sequences by posttranslation modification. a,p-Didehydro-a-amino acids have also been postulated to be precursors in the biosynthesis of several heterocyclic metabolites including penicillin and cephalosporin 9 Other well-known compounds containing ,( -di-dehydro-a-amino acids are nisin 10,11 (a food preservative112 ), subtilin (a broad spectrum antibiotic) 13 and some of the metabolites isolated from Streptomyces strains such as gri-seoviridin 14 ... 

Addition to alkynoic esters. Conjugate addition of oximes to alkynoic esters to provide ( j-alkenyl oxime ethers is catalyzed by PhjP. Interestingly, a-addition by phthalimide is observed. Such adducts are useful precursors of dehydro-a-amino acids. ... 

V-benzyloxycarbonyl-2,3-dehydro-a-amino acid-/-Bu-ester H2/ [Rh(cod)Me-DuPhos]BF4b) thienyl, N-Ts-pyrrolyl [16]... 

N-acyldehydrodipeptides were readily prepared either by the condensation of N -acyldehydro-a-amino acids with a-amino acid esters or by the reaction of the azlactones of dehydro-a-amino acid with a-amino acid esters (eq. 1). Asymmetric hydrogenation of the N-acyldehydrodipeptides thus obtained (eq. 2) was carried out by using rhodium complexes with a variety of chiral diphosphines such as -Br-Phenyl-CAPP (3), Ph-CAPP (3), (-)BPPM (4), (+)BPPM (4), (-)DIOP ( ), (+)DIOP ( ), diPAMP (6), Chiraphos (7), Prophos (S), BPPFA (9) and CBZ-Phe-PPM (Fig. 1)(10). The chiral catalysts were prepared in situ from chiral diphosphine ligand with [Rh(NBD)2l -CIO4 (NBD = norbomadiene). Typical results are summarized in Tables I-V. 

Eliminations. Protected dehydro-a-amino acids are formed from serine-type derivatives by elimination or from condensation of nitroalkanes with a-tosylglycines. There is a similar process for the transformation of enediones to 2-alkylidene-1,4-... 

The asymmetric hydrogenahon of dehydro-a-amino acid derivahves catalyzed by chiral rhodium-phosphine complexes is a successful example of an aqueous micellar system [Eq. (1)]. Normally, achvity and selectivity are decreased by changing from an organic solvent to water but the addihon of a small amount of a micelleforming amphiphile leads to a significant increase in the reaction rate and in the enanhoselectivity [13, 14]. 

Kolasa, T. An Effective Synthesis of a,P-Dehydro-a-amino Acid Derivatives from N-Acyl-N-hydroxy-a-amino Acid. Synthesis 1983, 539. 

Asymmetric Hydrogenation of Dehydro a-Amino Acids [a-(Acylamino)acrylic Acids and Esters]... 

A chelate of phenyl 4,6-0 -(R)-benzylidene-2,3-0 -bis (dlphenyIphos-phino)-B-D-glucopyranoslde with rhodium (I) gives a stable highly active catalyst for the hydrogenation of N-acyl-dehydro-a-amino acids yielding, in high enantiomeric excess, N-acyl-(S)-a-amino... 

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