Alanine catalyst

Furthermore, the choice of enyne substrates can lead to cyclized products that contain other functionalities than dienes. Very recently, Muller and Kressierer [148] have shown that yne allyl alcohols 200 can be rapidly cyclo-isomerized by a Pd2dba3-W-acetyl phenyl alanine catalyst system to furnish heterocyclic enals 202 in excellent yields (Scheme 82). The intermediate product of the enyne cycloisomerization in this case is the enol 201, which rapidly tautomerizes to the aldehyde 202. 

Kressierer and Muller [18] could also show that yne allyl alcohols are rapidly cycloisomerized by a Pdjdbaj—Af-acetyl phenyl alanine catalyst system to give silylsubstituted heterocyclic enals in excellent yields. This intriguing catalyst system is capable of performing a sequentially Pd-catalyzed processes as well as an acid-catalyzed iminium aldol condensation. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

To a solution of l. 47 g (0.03 mol) of sodium cyanide and 4.73 g (0.03 mol) of (-)-(.S)-x-methylbenzylamine hydrochloride in 5 mL of cold water is added 1 g (8.3 mmol) of free ( - )-(.S )-a-mcthylbcnzylaininc in 200 mL of CHjOH. 1.32 g (0.03 mol) of acetaldehyde is added at 0°C and the clear solution is kept at r.t. for five days. After evaporation of the solvent in vacuo, the residue is dissolved in 50 mL of 1 N HC1 and the solution is extracted twice with diethyl ether. After addition of 12 N HCl to adjust the acid concentration to approximately 5 N, the solution is retluxed for 6 h. The HCl is evaporated in vacuo and the residue is dried over sodium hydroxide. The crude. V-x-methylbenzylalaninc hydrochloride is dissolved in 200 mL of 50% ethanol and the pH is adjusted to 6.0 with NaHCOj. To this solution, 3.5 g of palladium hydroxide is added. After hydrogenolysis for 10 h, the catalyst is filtered off and washed with hot water. The filtrate is concentrated to 30%, and the pH is adjusted to 1 with dilute IIC1. The solution is evaporated to dryness and the alanine hydrochloride is extracted with three 20-inL portions of absolute ethanol. After cooling overnight at — 50°C, the precipitated salt is filtered. Pyridine is added to the alcoholic solution to precipitate crude alanine, which is dissolved in 2.5 mL of water. The pH is adjusted with pyridine to 5.5-6.0, and 10 mL of absolute ethanol arc added yield 0.45 g (17% over four steps) mp 290 C [a] 7 + 13.13 (0 = 2.32. 6 N IICi). 

The phosphotriesterase from Pseudomonas diminuta was shown to catalyze the enantioselective hydrolysis of several racemic phosphates (21), the Sp isomer reacting faster than the Rp compound [65,66]. Further improvements using directed evolution were achieved by first carrying out a restricted alanine-scan [67] (i.e. at predetermined amino acid positions alanine was introduced). Whenever an effect on activity/ enantioselectivity was observed, the position was defined as a hot spot. Subsequently, randomization at several hot spots was performed, which led to the identification of several highly (S)- or (R)-selective mutants [66]. A similar procedure was applied to the generation of mutant phosphotriesterases as catalysts in the kinetic resolution of racemic phosphonates [68]. 

Arthur L. Weber (1998), now working at the Seti Institute of the Ames Research Center at Moffett Field, reports the successful synthesis of amino acid thioesters from formose substrates (formaldehyde and glycolaldehyde) and ammonia synthesis of alanine and homoserine was possible when thiol catalysts were added to the reaction mixture. On the basis of his experimental results, Weber (1998) suggests the process shown in Fig. 7.10 to be a general prebiotic route to amino acid thioesters. 

Another hypothesis on homochirality involves interaction of biomolecules with minerals, either at rock surfaces or at the sea bottom thus, adsorption processes of biomolecules at chiral mineral surfaces have been studied. Klabunovskii and Thiemann (2000) used a large selection of analytical data, provided by other authors, to study whether natural, optically active quartz could have played a role in the emergence of optical activity on the primeval Earth. Some researchers consider it possible that enantioselective adsorption by one of the quartz species (L or D) could have led to the homochirality of biomolecules. Asymmetric adsorption at enantiomor-phic quartz crystals has been detected L-quartz preferentially adsorbs L-alanine. Asymmetrical hydrogenation using d- or L-quartz as active catalysts is also possible. However, if the information in a large number of publications is averaged out, as Klabunovskii and Thiemann could show, there is no clear preference in nature for one of the two enantiomorphic quartz structures. It is possible that rhomobohedral... 

The standard work of Evans [2] as well as a survey of the papers produced in the Journal of Labeled Compounds and Radiopharmaceuticals over the last 20 years shows that the main tritiation routes are as given in Tab. 13.1. One can immediately see that unlike most 14C-labeling routes they consist of one step and frequently involve a catalyst, which can be either homogeneous or heterogeneous. One should therefore be able to exploit the tremendous developments that have been made in catalysis in recent years to benefit tritiation procedures. Chirally catalyzed hydrogenation reactions (Knowles and Noyori were recently awarded the Nobel prize for chemistry for their work in this area, sharing it with Sharpless for his work on the equivalent oxidation reactions) immediately come to mind. Already optically active compounds such as tritiated 1-alanine, 1-tyrosine, 1-dopa, etc. have been prepared in this way. 

It appears that the molybdenum catalyst is more suited to the cross-metathesis of the sterically bulky vinylglycines. The cross-metathesis reaction of a similarly protected dehydro alanine gave only recovered starting material. 

Fig. 24.8) [122]. Whilst this protocol can be used to prepare 3-pyridyl-alanine derivatives [22], the corresponding 2-pyridyl-alanine cannot be made [122]. However, Adamczyk has prepared several 2-pyridyl-alanine analogues through hydrogenation of the pyridine-N-oxide substrates in 80-83% ee (see Fig. 24.8) [123]. In general, only when the 2- and 6-positions of the pyridine ring are occupied can 2-, 3- or 4-pyridyl-alanine derivatives be prepared, without nitrogen modification, via hydrogenation with [phospholane-Rh]+ catalysts [122-124].

The reaction can be run in an open flask because only a small amount of gas escapes. See Note 3. Sodium cyanide can be substituted for potassium cyanide if 2 g. of jS-alanine is also employed as a catalyst. 

R Lygo, J. Crosby, J. A Peterson, Enantioselective Alkylation of Alanine-Derived Imines Using Quaternary Ammonium Catalysts , Tetrahedron Lett. 1999, 40, 8671-8674. 

In fact, there are only two heterogeneous catalysts that reliably give high enantioselectivities (e.s. s) (90% e.e. or above). These are Raney nickel (or Ni/Si02) system modified with tartaric acid (TA) or alanine for hydrogenation of /(-kctocstcrs [12-30], and platinum-on-charcoal or platinum-on-alumina modified with cinchona alkaloids for the hydrogenation of a-ketoesters [31-73],... 

Oxidative polymerization of phenol derivatives is also important pathway in vivo, and one example is the formation of melanin from tyrosine catalyzed by the Cu enzyme, tyrosinase. The pathway from tyrosine to melanin is described by Raper (7) and Mason (8) as Scheme 8 the oxygenation of tyrosine to 4-(3,4-dihydro-xyphenyl)-L-alanin (dopa), its subsequent oxidation to dopaqui-none, its oxidative cyclization to dopachrome and succeeding decarboxylation to 5,6-dihydroxyindole, and the oxidative coupling of the products leads to the melanin polymer. The oxidation of dopa to melanin was attempted here by using Cu as the catalyst. 

Colonna, Julia et al. believed that polymer chain lengths having an average of ten or more leucine or alanine residues gave rise to active catalyst. We have carried out a full study using material prepared using an amino acid synthesiser and we can confirm that active catalyst is obtained when employing a decamer of (ij-leucine [20]. 

At this point it is impossible to guess the architecture of the active catalyst. The folding of 10-mers of leucine and alanine in organic solvents is clearly of critical importance, and studies are in progress to understand the preferred shapes. Obviously, in its active form the catalyst binds and activates peroxide anion and/or the electron-poor alkene near its chiral surface, perhaps in a chiral cavity, but the precise orientation of catalyst and reactants in the initial bondforming Michael reaction remains unsolved. 

A pH-dependent chemoselective catalytic reductive amination of a-keto acids, affording a-amino acids with HCOONH4 in water, was achieved using the complex 31 or its precursor 28 as the catalyst [51]. The formation rates of alanine and lactic acid from pyruvic acid exhibited a maximum value around pH 5 and pH 3, respectively, and therefore, alanine was obtained quite selectively (96%) with a small amount of lactic acid (4%) at pH 5 (Scheme 5.18). A variety of nonpolar, uncharged polar and charged polar amino acids were also synthesized in high yields. 

Miller and co-workers have taken a totally different approach to design an efficient catalyst for enantioselective acylation. Their strategy relied on the use of a pep-tide-based backbone incorporating a 3-(l-imidazolyl)-(5)-alanine unit as the catalytic core. Upon treatment with an achiral acyl source these biomimetic enantioselective acyl transfer catalysts allow the formation of an acyl imidazolium ion in proximity to the chiral environment generated by the folding of the peptide [3, 159-174]. 

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