A,p-Dehydroamino acids

OL, -Dehydroamino acids. N-Protected (Cbo and Boc) (3-hydroxy-a-amino acid esters (ethyl, benzyl) are converted into the corresponding a,p-dehydroamino acid derivatives by DAST and pyridine in CHiCl, at 0° (6.5-90% yield). The hydroxy group is probably converted into the —OSFiNlCiH,), derbative, which undergoes trans-e m -... 

Singh TP, Kaur P. Conformation and design of peptides with a,P-dehydroamino acid residues. Progr. Biophys. Mol. Biol. 1996 66 141-165. 

The p-monohydride intermediates 101a, b were detected when a low-temperature reaction of 27 with a P-dehydroamino acid, namely, methyl (E)-3-acetamido-2-butenoate 18 was conducted and in low-temperature hydrogenation of the equilibrium mixture of 3,18, and 103 (Scheme 1.28). Similarly to the enamide case, the intermediacy of the p-monohydride correlated with the sense of enantioselection, which was opposite to that observed for a-dehydroamino acids. 

Figure 13.23 Substrate-based stereocontrol in the bioreduction of a,p-dehydroamino acid derivatives.

Stueckler, C., Winkler, C.K., Hall, M., Hauer, B., Boimekessel, M., Zangger, K., and Faber, K. (2011) Stereo-controlled asymmetric bioreduction of a,p-dehydroamino acid derivatives. Adv. Synth. Catal., 353,1169-1173. 

The a,p-double bond in amino acid derivatives and peptides represents, in addition to the amino and carboxy groups, the introduction of a third highly reactive function into the molecule. It is therefore pertinent in a discussion of the a,P-dehydroamino acids to devote some attention to their primary addition products, such as derivatives of a-mercapto- and a-hydroxy-a-amino acids. Further topics relevant in this context are their relationship to P-hydroxy- and P-mercapto-a-amino acid derivatives (elimination-addition sequence), as well as syntheses and reactions of pyruvoylamino acids, which result from the hydrolysis of dehydropeptides and can possibly serve as precursors of the latter by condensation with amino acid amides. On the other hand, p,y- and y S-dehydroamino acids will be excluded from the scope of this discussion. The isolated double bonds of these compounds undergo the normal olefin reactions and display no unusual characteristics. 

Numerous a,P-dehydroamino acids have in recent years been identified as constituents of fungal metabolites. Their characterization and typical structural features are summarized in Table 1. In most of these metabolites, almost all of which are cyclic compounds (cyclopeptides or cyclodepsipeptides) and which frequently possess antibiotic properties, D-amino acids also occur. 

Amino acids with appropriate 3-substituents have frequently been employed as a,p-dehydroamino acid precursors, particularly in the form of peptide chain subunits. Elimination reactions from derivatives of P-hydroxy- and P-mercapto-a-amino acids are the examples most often encountered. Of less importance are amino acid derivatives with P-halogen substituents (38, 132, 337, 386, 394, 395), as these require more drastic elimination conditions. Mannich bases of monoalkyl acylaminomalonates have also found use as precursors of dehydroalanine derivatives (177, 438). 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

Essentially the same results were later obtained with various prochi-ral substrates a-dehydro amino acids, enamides, - P-dehydroamino acid, unsaturated phosphonate, ° and itaconic ester. All studied substrates reacted instantaneously with 28a, b at -100°C yielding high ee s of the hydrogenation products—either equal or comparable to the ee s observed in the corresponding catalytic reactions. - ... 

After the precatalyst is completely converted to the active catalyst Xq, three steps are required to form the desired reduction product. The first step is the coordination of dehydroamino acid (A) to the rhodium atom forming adducts (Xi) and (Xi ) through C=C as well as the protecting group carbonyl. The next step is the oxidative addition of hydrogen to form the intermediate (X2). The insertion of solvent (B) is the third step, removing the product (P) from X2 and regenerating Xq. Hence, the establishment of the kinetic model involves these three irreversible steps. 

The rhodium complexes of the ferrocene derivatives 39 have shown useful characteristics for the reduction of itaconates as well as dehydroamino acid derivatives [15, 167-170]. These compounds are hybrids between ferrocene-based ligands and the various other types. The P-chiral compounds, which in some ways are DIPAMP hybrids, showed tolerance for the reduction of N-methyl en-amides to produce N-methyl-a-amino acid derivatives [169-171]. 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

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