Aromatic side chain preparation

Etard reagents (chromyl chloride and some derivatives) suffer from the problem that occasionally they can exhibit a lack of selectivity and low yields. They are useful in the selective oxidation of aromatic side-chains to a carbonyl group, aldehyde or ketone but in many instances, the formation of the initial complex is slow and yields are low because of difficulties in the work-up which lead to undesired over-reaction. Attempts have been made to solve the problems by the use of sonication [134]. A simple preparation of the liquid reagent was proposed and the Etard reaction itself together with the hydrolytic step were conducted under sonication, with some success (Scheme 3.25). 

Phosphonamidate peptide analogues mimicking the P1...F3 substrate residues have been prepared and evaluated against a CHC mixture Table 8.5). Inhibitors with an aromatic side-chain in subsite P] are some 20-fold more effective than are those with an aliphatic one (compare (31) to (29) or (30), Table 8.S). An opposite, albeit less pronounced, preference at this site appears to exist for the ketone inhibitors for fi-CYlC ((17) vs. (25) and (21) vs. (26), Table 8.4). However, this difference could be attributable to a predominance of class II CHC in the mixture assayed in Table 8.5. Thus, comparisons of this sort must be made with caution. Introduction of a double bond into the Pi side-chain decreases the potency of the phosphonamidate by more than a factor of 10 ((41) vs. (42), Table 8.5), perhaps because of... 

In an effort to better characterize the topochemical relationship between the hydrophobic pocket in the chymotrypsin binding site and the aromatic side chain in the substrate, 3-azidophenylalanine has been prepared.1161 Conversion of 4-aminophenylalanine (21) into 3-azidophenylalanine (23) was carried out via 4-chloro-3-nitrophenyl intermediate 22 as outlined in Scheme 6. 

This method is mainly restricted to the synthesis of amino acids with aromatic side-chains since the required unsaturated azlactones [e.g. (30)] are most readily prepared using aromatic aldehydes. Typically, benzaldehyde condenses under the influence of base with the reactive methylene group in the azlactone (29) which is formed by the dehydration of benzoylglycine (28) when the latter is heated with acetic anhydride in the presence of sodium acetate (cf. Expt 8.21). The azlactone ring is readily cleaved hydrolytically and compounds of the type (30) yield substituted acylaminoacrylic acids [e.g. (31)] on boiling with water. Reduction and further hydrolysis yields the amino acid [e.g. phenylalanine,... 

Carboxylic acids are prepared by at least four methods (1) by oxidation of primary alcohols or aldehydes, (2) by oxidation of an aromatic side chain, (3) from a Grignard reagent and carbon dioxide, or (4) by hydrolysis of a nitrile, RC=N. 

As a first step toward this purpose, we have studied the chelation effect of tetrapeptides of sequences Cys-X-Y-Cys, by preparation of metal complexes of mainly the first transition series. The hydrophobic effect of the peptides was also studied by utilizing the side chain bulkiness of the amino acid residues interposed between the two cysteine residues. A special effect of aromatic side chains of tyrosine, phenylalanine, and tryptophan has also been examined in order to assess their ability to ease electron transfer to and from the nearby iron core. 

Conversion of existing functions include the oxidation of aliphatic or aromatic side-chains, one of the earliest preparative techniques of triazole chemistry. Hydrolysis of cyanides obtained by displacement of halo, nitro and diazo groups is of comparable importance. 

Nickel peroxide, an undefined black oxide of nickel, is prepared from nickel sulfate hexahydrate by oxidation in alkaline medium with an ozone-oxygen mixture [929] or with sodium hypochlorite [930, 931, 932, 933]. Its main applications are the oxidation of aromatic side chains to carboxyls [933], of allylic and benzylic alcohols to aldehydes in organic solvents [929, 932] or to acids in aqueous alkaline solutions [929, 930, 932], and of aldehydes to acids [934, the conversion of aldehyde or ketone hydrazones into diazo compounds [935] the dehydrogenative coupling of ketones in the a positions with respect to carbonyl groups [931] and the dehydrogenation of primary amines to nitriles or azo compounds [936]. 

In the mid to late 1980s, many research groups focused on methods and processes to prepare L-phenylalanine (see Chapter 4, this book by Fotheringham). This was a direct result of the demand for the synthetic, artificial sweetener aspartame. One of the many routes studied was the use of phenylalanine dH (Scheme 3, R = C6H5CH2) with phenylpyruvate (PPA) as substrate [41,42]. This enzyme from Bacillus sphaericus shows a broad substrate specificity and, thus, has been used to prepare a number of derivatives of L-phenylalanine [43]. A phenylalanine dH isolated from a Rhodococcus strain M4 has been used to make L-homophenyl-alanine [(5)-2-amino-4-phenylbutanoic acid], a key chiral component in many angiotensin-converting enzyme (ACE) inhibitors [30]. More recently, that same phenylalanine dH has been used to synthesize a number of other unnatural amino acids that do not contain an aromatic side chain [33]. 

A variety of penicillins have been produced by the fermentation of Penidl-lium chrysogenum in the presence of different nutrients. Penicillin G (ben-zylpenicilbn see Figure 1) predominates when the culture medium is rich in phenylacetic acid, whereas the incorporation of phenoxyacetic acid favors penicillin V (phenoxymethylpenicillin). Semisynthetic penicillins, such as ampicillin and amoxicillin, are prepared by replacing the aromatic side chain of biosynthetically derived penicillins with other chemical groups. All peni-cilhns are j8-lactam (see Figure 2) antibiotics and have the same mechanism of action They inhibit bacterial cell wall biosynthesis. 

Preparation of the Aromatic Side Chain UUman Methoxylation in the Presence of a Protected Aniline... 

Resolution of 19 pairs of DL-proteinogenic AAs, containing neutral, acidic, basic, or aromatic side chains, by HPLC, was made possible with three chiral variants of MR prepared by the reaction of DFDNB with Val-NH2, Phe-NH2, and Pro-NH2. Differences in AIr (retention times) of these diastereomers were compared with those obtained by derivatization of the same set of 19 dl-AAs with the original MR [20]. However, the FDNP-Val-NH2 gave the largest AIr values. 

TTie true ketones, in which the >CO group is in the side chain, the most common examples being acetophenone or methyl phenyl ketone, C HjCOCH, and benzophenone or diphenyl ketone, C HjCOC(Hj. These ketones are usually prepared by a modification of the Friedel-Crafts reaction, an aromatic hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic) in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride... 

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