Benzophenones side chain

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... 

A third modality is based on the use of orthogonal protection during SPPS synthesis to achieve selective removal of a specific side-chain protecting group, followed by selective modification with an activated benzophenone moiety. At the conclusion of the side-chain modification, which is carried out on the resin-bound peptide, stepwise elongation of the peptide chain is resumed.11571 Table 5 provides a current summary of reported biologically active peptides substituted with a benzophenone moiety and includes some synthetic details about their preparation. 

Fig. 18.4. Mechanism for the photochemical reaction of a benzophenone-coated ITO-modified optical fiber with a C-H bond of an amino acid side chain of the hepatitis C virus. The virus can act as an antigen for the detection of the anti-HCV antibody. After the immunoreaction, the subsequent binding of a marker, a secondary peroxidase-labeled antibody, allowed to catalyze a chemiluminescence reaction for the receipt of an optical signal.

In the recent literature, many examples of A/BPs containing benzophenones can be found. A first example concerns the study of HDACs. These enzymes catalyze the hydrolysis of acetylated lysine amine side chains in histones and are thus involved in the regulation of gene expression. There are approximately 20 human HDACs, which are divided into three classes (I, II, and III). Class I and II HDACs are zinc-dependent metallohydrolases that do not form a covalent bond with their substrates during their catalytic process, which is similar to MMPs. It has been found that hydroxamate 65 (SAHA, see Fig. 5) is a potent reversible inhibitor of class I and II HDACs. In 2007, Cravatt and coworkers reported the transformation of SAHA into an A/BP by installment of a benzophenone and an alkyne moiety, which resulted in SAHA-BPyne (66) [73]. They showed that the probe can be used for the covalent modification and enrichment of several class I and class II HDACs from complex proteomes in an activity-dependent manner. In addition, they identified several HDAC-associated proteins, possibly arising from the tight interaction with HDACs. Also, the probe was used to measure differences in HDAC content in human disease models. Later they reported the construction of a library of related probes and studied the differences in HDAC labeling [74], Their most... 

Fig. 6 Examples of benzophenone-modified probes to target matrix metalloproteinases. The amino acid three letter abbreviations in the R, (73a,b) and R (74) substituents refer to their corresponding side chains...

Side-chain aromatic radicals of the type Ph—CR—OH cannot be produced efficiently by reaction of OH with the alcohol because OH tends to add to the aromatic ring more efficiently. They are, therefore, produced by addition of an electron to the carbonyl compound. The pRwalues for the acetophenone and benzophenone ketyl radicals are 9-5 and they are affected by substituents on the aromatic ring as well as by those directly at the radical site. ... 

The search for endothelin antagonists as potential compounds for treating cardiovascular disease was noted in Chapter 5 (see atrasentan). A composed with a considerably simpler structure incorporates a pyrimidine ring in the side chain. Condensation of benzophenone (94) with ethyl chloro-acetate and sodium methoxide initially proceeds to addition of the enolate from the acetate to the benzophenone carbonyl. The aUcoxide anion on the first-formed quaternary carbon then displaces chlorine on the acetate to leave behind the oxirane in the observed product (95). Methanolysis of the epoxide in the product in the presence of boron triflor-ide leads to the ether-alcohol (96). Reaction of this with the pyrimidine (97) in the presence of base leads to displacement of the methanesulfonyl group by the aUcoxide from 96. Saponification of the ester group in that product gives the corresponding acid, ambrisentan (98). " ... 

Aromatic ketones may contain one aryl ring and one alkyl chain, such as acetophenone (2), or two aryl rings such as benzophenone (diphenyl-methanone, 4), Molecules containing a carbonyl group in a side chain show normal aliphatic behaviour and are not considered here. Aromatic ketones generally behave in a similar manner to aldehydes (see Scheme 6.9) but are slightly less reactive. 

A benzyl side chain is chanjged to a benzoyl group by vigorous oxidation. For example, 4,4 -diacetylaminodiphenylmethane is converted with chromic acid to the benzophenone in 70% yield. Also, 2-benzoyl-... 

UV irradiation of poly(4-vinylbenzophenone) [poly(VBP)] in benzene solution, and in the presence of isopropanol as hydrogen donor, gives rise to a more complex picture [12,13]. Indeed, intra- and inter-molecular coupling reactions by the side-chain benzophenone ketyl radicals (K ) markedly change the macro-molecular morphology with the occurrence of cyclic and network structures as well as chain scission processes (Scheme 5). 

On the basis of the above described results, tailor-made benzophenone-containing polymeric photoinitiators have been studied in order to establish the effect of the relative distance from the polymer chain of the side-chain benzophenone groups. Thus, the homopolymer of Uvecryl P36 [poly(UP36)] and its copolymers with MtA [poly(UP36-co-MtA)s], bearing the benzophenone moiety at quite a large distance from the backbone, have been checked as photoinitiators in the polymerization of the HDDA/BA equimolar mixture against poly(ABP), poly(VBP) and poly(VBP-co-MtA)s [20-22]. 

In conclusion, on the basis of the collected results, polymeric photoinitiators bearing side-chain benzophenone moieties show, at least under nitrogen atmosphere, a large improvement of activity as comjMred with low-molecular-weight structural models. Pol)rmeric systems having even higher activity can easily be prepared by introducing in the macromolecules, via a copolymerization route. 

Table 12. UV curing in film matrix of HDDA/BA equimolar mixture, under nitrogen, by polymeric photoinitiators bearing both benzophenone and tertiary amine moieties in the side chain [18,22, 53]...

With the aim of improving the photoinitiation activity of benzophenone/tertiary amine containing polymers, new polymeric systems having flexible spacers of different length inserted between the above side-chain functional groups and the backbone, have been proposed [22]. Indeed, copolymers of ABP, VBP... 

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