Phenylacetyl group

The a-carbon atom of the phenylacetyl group is more susceptible to attack by the basic catalyst (triethylamine) than the acetyl group hence a-phenyl-cinnamic acid, but no cinnamic acid, is obtained. 

Lipase Fp from Amano, vinyl acetate, 4 h, 90% yield. This method can also be used for the selective introduction of other esters, such as the methoxyacetyl, phenoxyacetyl, and phenylacetyl groups, in excellent yield. 

The building blocks for the biosynthesis of benzylpenicillin are three amino acids, a-aminoadipic acid, cysteine and valine, and PAA. The amino acids condense to a tripeptide, ring closure of which gives the penicillin ring structure with an cu-aminoadipyl side-chain, isopenicillin N. The side-chain is then displayed by a phenylacetyl group from PAA to give benzylpenicillin. 

Not unexpectedly, alkylation of the double carbonylated complex proceeds via a base-catalysed interfacial enolization step, but it is significant that the initial double carbonylation step also involves an interfacial reaction, as it has been shown that no pyruvic acid derivatives are obtained at low stirring rates. Further evidence comes from observations of the cobalt-catalysed carbonylation of secondary benzyl halides [8], where the overall reaction is more complex than that indicated by Scheme 8.3. In addition to the expected formation of the phenylacetic and phenylpyruvic acids, the reaction with 1-bromo-l-phenylethane also produces 3-phenylpropionic acid, 2,3-diphenylbutane, ethylbenzene and styrene (Scheme 8.4). The absence of secondary carbonylation of the phenylpropionylcobalt tetracarbonyl complex is consistent with the less favourable enolization of the phenylpropionyl group, compared with the phenylacetyl group. 

Penicillin is but one of a series of closely related compounds isolated from fermentation broths of Penicillium notatum. This compound, also known as penicillin G (1-1) or benzyl penicillin, is quite unstable and quickly eliminated from the body. Initial approaches to solving these problems, as noted above, consisted of preparing salts of the compound with amines that would form tight ion pairs that in effect provided a controlled release of the active dmg. Research on fermentation conditions aimed at optimizing fermentation yields succeeded to the point where penicillin G or penicillin V (26-1), in which the phenylacetyl group is replaced by phenoxyacetyl, is now considered a commodity chemical. Another result of this research was the identification of fermentation conditions that favored the formation of the deacylated primary amine, 6-aminopenicillanic acid (2-4) or 6-APA, a compound that provided the key to semisynthetic compounds with superior pharmaceutical properties than the natural material. An elegant procedure for the removal of the amide side chain proved competitive with 6-APA from fermentation. This method, which is equally applicable to penicillin V, starts by conversion of the acid to the corresponding silyl ester (2-1). Treatment of that compound with phosphoms pentachloride in the... 

The Fujii group has also applied their strategy to the regio- and stereoselective deprotection of acylated sugars.34 They designed the phosphonylated glucose derivative 22 in which the two 4-(A -acetylamino)phenylacetyl groups at C-3 and... 

An additional interesting acyl-type -protection is the phenylacetyl group that is enzymatically removed with penicillin G acylase (see Section 2.5). 

Scheme 5 The Penicillin G Acylase Mediated Deprotection of a Phenylacetyl Group in the Synthesis of l-Deamino-Lys8-vasopressinl l O...

After peptide chain extension and disulfide bond formation by oxidative cyclization, the phenylacetyl group could be removed enzymatically in 74% yield. The technique has been applied further in the synthesis of even larger peptides, for example in the deprotection of tris(phenylacetamido)porcine insulin.P l Since PGA is commercially available and devoid of any peptidase activity, this method appears to be generally useful for the construction of lysine-containing oligopeptides. 

Scheme 6 Enzymatic Selective Removal of the N-Terminal Phenylacetyl Group in the Synthesis of Phospho-peptidesl - ...

In another case, 1 was used to deprotect the 2-(allyloxy)phenylacetyl group, employed as a protecting functionality in carbohydrate chemistry242. Thus, heating compound 266 with a palladium catalyst/proton sponge system results in an almost quantitative yield of compound 268 (equation 29). In accordance with a postulated relay mechanism, the phenolic allyl ether is cleaved by the transition metal followed by intramolecular ester cleavage by nucleophilic attack of the released hydroxyl. The aforementioned conditions... 

Figure 6.14 Enzymatic side chain cieavage of penidliins. 6-Aminopenicillanic acid, a vaiuabie intermediate for the production of various semi-synthetic penicillins, can be obtain through enzyme-mediated hydrolysis of the phenylacetyl group of penicillin G or the phenoxyacetyi group of penicillin V. The active site of the enzyme recognises the aromatic side chain and the amide linkage, rather than the penidllin nucleus. Chemical entities other than penicillins are therefore often good substrates, as long as they contain the aromatic acetamide moiety.

As an alternative to the well established phenylacetyl group in (3-lactam chemistry, recently a biocatalyzed procedure for the removal of phthalyl imide has been described (Fig. 18-2)[45, 71 Its general usefulness remains to be demonstrated, however. 

AminopeniciIlanic acid is prepared from penicillin G by cleavage of the phenylacetyl group. In the early 1960s, penicillin G-acylase was used for this. However, the process was inefficient by present-day criteria, since the space/ time yield was low and the enzyme could not be reused. Therefore, a chemical solution to the problem was sought. 

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