Hydrogenation Of Dehydroamino Acids Research Articles

Peptide backbone modifications in lanthipeptides.

Lanthipeptides are a class of ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products characterized by the presence of lanthionine and methyllanthionine. During the maturation of select lanthipeptides, five different alterations have been observed to the chemical structure of the peptide backbone. First, dehydratases generate dehydroalanine and dehydrobutyrine from Ser or Thr residues, respectively. A second example of introduction of unsaturation is the oxidative decarboxylation of C-terminal Cys residues catalyzed by the decarboxylase LanD. Both modifications result in loss of chirality at the α-carbon of the amino acid residues. Attack of a cysteine thiol onto a dehydrated amino acid results in thioether crosslink formation with either inversion or retention of the l-stereochemical configuration at the α-carbon of former Ser and Thr residues. A fourth modification of the protein backbone is the hydrogenation of dehydroamino acids to afford d-amino acids catalyzed by NAD(P)H-dependent reductases. A fifth modification is the conversion of Asp to isoAsp. Herein, the methods used to produce and characterize the lanthipeptide bicereucin will be described in detail along with a brief overview of other lanthipeptides.

“In situ immobilization” of a multicomponent chiral catalyst (MCC) via non-covalent interactions for heterogeneous asymmetric hydrogenation reactions

Novel hybrid catalysts that resulted from the anchoring of pyrene-tagged Rh(i) complexes onto graphene materials via π–π stacking interactions show excellent catalytic activity towards the hydrogenation of dehydroamino acid.

Attracting Enantiomers: Chiral Analytes That Are Simultaneously Shift Reagents Allow Rapid Screening of Enantiomeric Ratios by NMR Spectroscopy.

The rapid and direct determination of enantiomeric ratios is of increasing interest due to the significantly reduced effort compared to chromatographic methods and the large number of analytes, for instance in enantioselective catalysis. Current strategies include colorimetric assays, (a)chiral solvating reagents for NMR spectroscopy and metal complexes for CD sensing. We report the determination of enantiomeric ratios based on the self-induced diastereomeric anisochronism (SIDA) effect. Alanine derivatives that represent chiral products of enantioselective catalysis, such as the well-established hydrogenation of dehydroamino acids, were investigated. The SIDA effect was significantly enhanced by attachment of 3,5-dinitrobenzoyl π-π interactions sites. This simple modification enabled simultaneous determination of enantiomeric ratios and conversions by NMR spectroscopy.

ChemInform Abstract: Synthesis and Evaluation of a Broad Range of New Chiral Phosphine—Carbene Ligands for Asymmetric Hydrogenation.

AbstractThe novel catalysts of the type (I) are synthesized on a gram scale and applied in the hydrogenation of dehydroamino acids (II) and methylstilbene (IV).

Modular optimization of enantiopure epoxide-derived P,S-ligands for rhodium-catalyzed hydrogenation of dehydroamino acids

The optimization of P,S-ligands derived from enantiopure (2S,3S)-phenylglycidol for asymmetric rhodium-catalyzed hydrogenation of dehydroamino esters is described. The exceptionally high modular character of the (2S,3S)-phenylglycidol platform is demonstrated by systematic modification of the ether and thioether moieties, the skeletal aryl substituent and the stereo and regiochemistry of the ligands. An experimentally useful method for the monitoring of hydrogenation reactions is also described and used for obtaining relevant data of the catalytic systems studied.

Highly stereoselective and efficient synthesis of the dopa analogue in pepticinnamin E via enantioselective hydrogenation of dehydroamino acids

An efficient and new method was developed to prepare the dopa analogue 11 in natural pepticinnamin via catalytic hydrogenation of dehydroamino acids (DDAA) with a good yield and ee. Product 11 is a key intermediate towards the total synthesis of pepticinnamin E and its analogues.

Rhodium-Catalyzed Asymmetric Hydrogenation

In this paper the authors report the synthesis and resolution of 3,3′-disubstituted xylBINAP derivatives and their application as ligands for rhodium-catalyzed asymmetric hydrogenation of dehydroamino acids and enamides. Under optimized conditions ligand 5, bearing chiral moieties at the 3,3′-positions, demonstrated excellent ­results for hydrogenation of methyl N-acetamido cinnamic acid (>99% ee).

Synthesis and Resolution of 3,3′-Disubstituted xylBINAP Derivatives and Their Application in Rhodium-Catalyzed Asymmetric Hydrogenation

A novel class of 3,3'-disubstituted xylBINAP ligands have been synthesized and tested in the hydrogenations of substituted olefins. This new substitution pattern has demonstrated that the 3,5-dialkyl meta effect and 3,3'-disubstitution can operate in a synergistic fashion in Rh-catalyzed hydrogenation of dehydroamino acids. Notably, (S ax )-8 outperforms BINAP, xylBINAP and previously reported 3,3'-disubstituted BINAP derivatives in the hydrogenation of methyl N-acetamido cinnamate.

Comparison of supports for the electrostatic immobilisation of asymmetric homogeneous catalysts

To determine the influence of the support on the asymmetric hydrogenation of dehydroamino acids using noncovalently immobilised catalysts, Rhodium-MonoPhos was successfully immobilised on four different anionic carrier materials: a mesoporous aluminosilicate (AlTUD-1), phosphotungstic acid on alumina (PWTUD), Nafion, and a Nafion silica composite (SAC-13). These supported catalysts were evaluated in the asymmetric reduction of methyl-2-acetamidoacrylate. Although most of the catalysts were highly selective, the activity and the loss of rhodium were strongly dependent on the type of support. PWTUD appeared to be the best support for this application, because it gave the catalyst with the highest activity and virtually no leaching in any solvent. Its superior anchoring ability derives from the additional bonding between the Rh and the phosphotungstic acid. Nafion, on the other hand, was by far the poorest support, giving very low activity. Immobilisation with this support relies on encapsulation rather than on ionic interactions. Its encapsulating properties not only prevent the complex from going into solution, but also prevent the substrate from reaching the catalytic site.

Asymmetric hydrogenation of enamides with a new chiral phosphine–phosphinite ligand

A new mixed chiral phosphine–phosphinite 4 obtained from enantiomerically pure ( S)-(+)-3-boronatodiphenyl-phosphanyl butanoic acid 1 was synthesized in four steps. This new chiral ligand was used in the asymmetric hydrogenation of dehydroamino acids with enantioselectivities being obtained of up to 90.8%.

Evidence for the importance of conformational equilibria in Rh-diphosphine complexes for the enantioselection in Rh-catalyzed asymmetric hydrogenation

The conformations of the chelate cycles in the X-ray structures of norbornadiene- and cyclooctadiene-rhodium complexes of ( R, R)-1,2-bis[( o-methylphenyl)phenylphosphino]ethane are dramatically different. Nevertheless, they demonstrate the same sense of enantioselection in asymmetric hydrogenation of dehydroamino acids.

ジホスフィンロジウムおよびルテニウム錯体を用いるデヒドロアミノ酸類の触媒的不斉水素化の機構研究の新展開

The Rh-catalyzed enantioselective hydrogenation of N-acylated dehydroamino acids or their esters, initiated by Kagan, constitutes now a standard tool for the synthesis of natural and unnatural amino acids of high enantiomeric purity. The reaction proceeds via the unsaturate-dihydride mechanism in which the oxidative addition of hydrogen to Rh-enamide complex is the rate-limiting and stereodifferentiating step. In addition to this standard pathway, alternative dihydrideunsaturate mechanisms have also been reported. The formation of a RhH2 may precede the olefin-Rh interaction, depending on the chiral ligands and reaction conditions. Reactions using BINAP-Ru (II) complexes (BINAP = 2, 2'-bis (diphenylphosphino) -1, 1'-binaphthyl), find a wider synthetic scope, allowing asymmetric hydrogenation of a range of functionalized olefins and ketones. Interestingly, the Rh and Ru complexes with the same BINAP ligand exhibit an opposite sense of asymmetric induction in hydrogenation of dehydroamino acid derivatives. This review summarizes some mechanistic studies in this hydrogenation catalyzed by diphosphine-Rh and-Ru complexes.

Catechol‐Based Phosphoramidites: A New Class of Chiral Ligands for Rhodium‐Catalyzed Asymmetric Hydrogenations.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Efficient Synthesis of (2S,6S)- and meso-Diaminopimelic Acids via Asymmetric Hydrogenation

An efficient synthesis of the title compounds l and 2 has been successfully developed. The key step is the asymmetric hydrogenation of dehydroamino acid 7 using [Rh(I)(COD)-(S,S) or -(R,R)-Et-DuPHOS)] + OTf to produce the optically active, protected amino acid derivatives in high ee (>95%) The approach also can he used for the synthesis of other isomers and analogues.

Catechol-based phosphoramidites: a new class of chiral ligands for rhodium-catalyzed asymmetric hydrogenations.

[reaction: see text] The synthesis and application of a new class of catechol-based phosphoramidites is described. Ees up to 99% were obtained in the rhodium-catalyzed asymmetric hydrogenation of dehydroamino acids and enamides.

Ligand Tuning as a Tool for the Discovery of New Catalytic Asymmetric Processes

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ligand Tuning as a Tool for the Discovery of New Catalytic Asymmetric Processes

In this era of heightened environmental awareness and ever-increasing demand for higher efficiency from chemical processes, one of the major challenges facing organic synthesis is the utilization of abundantly available carbon sources as precursors for more advanced intermediates. The dual problems of activation of thermodynamically stable precursors and their stereoselective incorporation pose new challenges, solutions of which may have broader implications in asymmetric catalysis. This review summarizes our recent efforts to discover broadly applicable control elements in key enantioselective carbon-carbon and carbon-hydrogen bondforming reactions. Transition metal complexes of 1,2-diol phosphinites derived from readily available monosaccharides catalyze a variety of asymmetric reactions of prochiral olefins including Markovnikov addition of HCN to vinyl arenes and hydrogenation of dehydroamino acids. Enantioselectivities of these reactions can be optimized through steric and electronic tuning of the bis-phosphinite ligand system. Both R and S enantiomers of the precursors of protoptypical 2-arylpropionic acids and of various α-amino acids can be prepared by these routes. We have also discovered new protocols for a nearly quantitative and highly selective codimerization of ethylene or propylene, and various functionalized vinylarenes and strained olefins. Various strategies for stereochemical control in an enantioselective version of this reaction will be discussed. These include design and synthesis of new ligands and applications of the ‘hemi-labile ligand concept’. During these investigations important synergistic relationships between such ligands and coordinating properties of various counter ions were also uncovered. These discoveries may contribute to the discovery of more selective homogeneous catalysts. Keywords: ligand tuning, catalytic asymmetric process, homogeneous asymmetric catalysis

Monodentate Phosphoramidites: A Breakthrough in Rhodium‐Catalysed Asymmetric Hydrogenation of Olefins

AbstractMonodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium‐catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos (7a) the simplest member of this class, a ligand that is prepared in a single step from BINOL and HMPT. Turnover numbers up to 6000 have been obtained in the hydrogenation of dehydroamino acid derivatives. Enantioselectivities in the hydrogenation of dehydroamino acids are solvent dependent; in non‐protic solvents they range from 95–99%. Itaconic acid and its dimethyl ester could be hydrogenated with 96 and 94% e.e., respectively. Hydrogenation of aromatic enamides gave the corresponding acylated amines in 86–94% e.e. Several analogous phosphoramidite ligands have been prepared. Surprisingly, bidentate ligands gave poorer results, both in terms of rate as well as enantioselectivity. Taddol‐based phosphoramidites led to poor e.e. and slow rates. Methyl substituents at the 3,3′‐position of BINOL led to a sharply reduced rate and a somewhat lower enantioselectivity. Bromo substituents at the 6,6′‐position led to a slightly reduced rate but little effect was seen on enantioselectivity. Use of octahydro‐MonoPhos (11) gave results that were very similar to those obtained with 7a. The rate of the reaction is dependent on the hydrogen pressure, however, the enantioselectivity is not affected. The rate of the dehydroamino acid hydrogenation also increases if the ligand to rhodium ratio is reduced from 2.2 to 1.5 or even to 1.0; yet, there is no deleterious effect on the enantioselectivity. Catalytic activity ceases with L/Rh=3 when dehydroamino acid derivatives were used as substrate. The reaction shows a positive non‐linear effect, which confirms the presence of Rh‐complexes with more than one ligand. Following the hydrogenation of methyl 2‐acetamidocinnnamate with Rh(nbd)2BF4/7a by electrospray mass spectrometry showed the presence of several rhodium species. Notable are the presence of [Rh(7a)]3+ and [Rh(7a)]4+. There is at present insufficient evidence to conclude if the active catalytic species carries one or two ligands. In view of the low cost of MonoPhos this invention might well lead to a broader application of asymmetric olefin hydrogenation for the production of enantiopure amino acids and amines.

Monodentate Chiral Spiro Phosphoramidites: Efficient Ligands for Rhodium‐Catalyzed Enantioselective Hydrogenation of Enamides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rhodium/MonoPhos-Catalysed Asymmetric Hydrogenation of Enamides

The monodentate phosphoramidite MonoPhos has been used in the rhodium-catalysed asymmetric hydrogenation of N-acetyl-α-arylenamides. This ligand is readily available via a one-step procedure and is air stable. Its Rh(I) complex, which is an effective catalyst precursor for the hydrogenation of dehydroamino acids, also gives high enantioselectivities for this class of substrates. Because of the facile synthesis and stability of MonoPhos, its complex provides a general solution in preparing chiral amine derivatives through asymmetric hydrogenation.