Hydroxy amino acids synthesis

A second, conceptually distinct chiral synthesis of monobactams was developed from P-hydroxy amino acids. As shown in Figure 2, cycli2ation of the acylsulfamate of an amino-protected 0-mesylserine derivative (14, R = H) leads directiy to the monobactam (15). This methodology was also appHed to the synthesis of 4a- (15, R = CH ) and 4P-methyl monobactams from L-threonine and aHothreonine, respectively (17). The... 

The photoelectrochemical synthesis of amino acids from simple molecules has also been reported. Low efficiencies were observed in the conversion of mixtures of methane, ammonia and water to several amino acids on platinized TiOz Amino acids and peptides were reported when glucose replaced methane as the carbon source in a parallel experiment Higher quantum efficiencies (20-40%) were observed in the conversion of alpha-keto acids or alpha-hydroxy acids to the corresponding alpha-amino acids Moderate levels of enantiomeric selectivity (optical yields of about 50%) were reported when chiral starting materials were employed. Photoinduced Michael-like reactions were observed when alpha, beta unsaturated acids were used as substrates for the amino acid synthesis... 

M. T. Reetz, T. Winsch, and K. Harms, Stereoselective synthesis of a, y-diamino-(3-hydroxy amino acid esters A new class of amino acids, Tetrahedron Asymm. 7 371 (1990). 

This synthesis of amino acids, called the Strecker synthesis, requires the presence of NH4+ (and NH3) in the primitive ocean. On the basis of the experimental equilibrium and rate constants it can be shown16 that equal amounts of amino and hydroxy acids are obtained when the NH4+ concentration is about 0.01 M at pH 8 and 25°C with this NH4+ concentration being insensitive to temperature and pH. This translates into a pNH3 in the atmosphere of 2 x 1(U7 atm at 0° and 4 x 10-6 atm at 25°C. This is a low partial pressure, but it would seem to be necessary for amino acid synthesis. Ammonia is decomposed by ultraviolet light, but mechanisms for resynthesis are available. The details of the ammonia balance on the primitive earth remain to be worked out. 

Four mechanisms have been advanced for the prebiotic formation of amino acids. The first involves a cyanohydrin (reaction 2) and a related route (reaction 3) can be invoked to account for the presence of hydroxy acids. These particular reactions have been studied in considerable detail both kinetically and in terms of thermodynamic quantities.347 An alternative route (4) involves the hydrolysis of a-aminonitriles, which are themselves formed directly in anhydrous CH4/NH3 mixtures.344 Cyanoacetylene, formed in CH4/N2 irradiations,349 yields significant amounts of asparagine and aspartic acids (reaction 5). Finally, a number of workers336,350"354 have proposed that HCN oligomers, especially the trimer aminoacetonitrile and the tetramer diaminomaleonitrile, could have been important precursors for amino acid synthesis. Reaction mixtures involving such species have yielded up to 12 amino acids. Table 11 indicates the range of amino acids produced in these kinds of sparking syntheses. Of some interest is the fact that close parallels between these kinds of experiments and amino acid contents of carbonaceous chondrite meteorites exist.331,355,356... 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

In its utilization of acetonitrile, the oxazoline synthesis shown in Scheme 56 resembles a Ritter reaction.The procedure is convenient, but yields are variable the pyrolysis gives starting alkene plus acetamide as by-products. Another oxazoline synthesis and subsequent conversion to a cif-amino alcohol is discussed later (Scheme 85). A recent y-hydroxy-a-amino acid synthesis incorporates the following type of transformation (Scheme 57).If a three-day equilibration with anhydrous HBr was introduced iMtween stages i and ii, almost pure trans product was obtained. The paper has many usefol references. Yet another modified Ritter reaction is shown in Scheme 58. ... 

Fltlbener, G., Goehring, W., Musiol, FI. J., and Moroder, L. (1992) N-a-tri-fluoroacetylation of N-terminal hydroxy amino acids a new side reaction in peptide synthesis. Peptide Res. 5, 287-292. 

The trimethylsilyl group was the first to be developed and is widely used for the protection of serine and threonine (Table 6). Chlorotrimethylsilane, l,14 3,3,3-hexamethyldisilazane, and A(0-bis(trimethylsilyl)acetamide are commercially available reagents used for the conversion of alcohols into the corresponding trimethylsilyl derivatives.Furthermore, trimethylsilyl cyanide has been used to protect the side chains of serine, threonine, and ty-rosine.f This silyl protection allows the formation of A -carboxyanhydrides from H-Ser(TMS)-OH and H-Thr(TMS)-OH, and their application in peptide synthesis in the aqueous phase.f l The TMS group can be removed under various conditions, depending on the kind of functional group to which it is bound the TMS ethers are more stable than related amino or carboxy derivatives.These differences in stability allow the direct application of completely silylated hydroxy amino acids in peptide synthesis.b ... 

Silyl ethers of hydroxy amino acids have been employed in both solid-phase and solution peptide synthesis. Since the TBDMS and TBDPS ether groups are stable to piperidine and other basic reagents, these derivatives of Ser and Thr (Tables 8 and 9) can be used in the Fmoc strategy.Homodetic peptides and depsipeptides have also been synthesized using TBDMS hydroxy protection for phenyllactic acid and hydroxyisovaleric acid, respectively. 

The condensation of organolithium reagents (2 equiv.) with glyoxylate-derived oxime ethers (182) provides a direct method for the synthesis of a- -hydroxy amino acids (equation 22). Both glyoxylic acid and glyoxylamide oxime ethers are compatible with this process. A(>hydroxyaminoacetamides are also product in low/moderate yields by the addition of isonitriles to oximes (oxime ethers) analogous to the four component condensation described by Ugi. ... 

Reagent (I) proved to be especially useful in the case of unprotected hydroxy amino acids as examplified by the synthesis of Boc-L-Serine and Boc-L-Tyrosine [See table 3-26]. 

The first synthesis of a siderophore was the preparation of ferrioxamine B over 20 years ago in order to confirm the chemical structure of this natural product67). Synthesis of the other hydroxamate containing siderophores has as a central problem preparation of the constituent to-N-hydroxy amino acid in an optically pure form. The most important such subunit in hydroxamate siderophores is Ns-hydroxy ornithine. This is a chiral building block of the diketopiperazine-containing siderophores (rhodo-torulic acid 68), dimerum acid 69), coprogen 70) and coprogen B 69>), the cyclic hexa-peptides of the ferrichrome family27), the fusarinines 71 -73) and the antibiotic ferri-chrome derivatives albomycines Sl5 S2 and e 61-62). 

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