A-carboxyl group, protection

The SEM ester was used to protect a carboxyl group where DCC-mediated esterification caused destruction of the substrate. It was formed from the acid and SEM chloride (THF, 0°, 80% yield) and was removed solvolytically. The ease of removal in this case was attributed to anchimeric assistance by the phosphate group. Normally SEM groups are cleaved by treatment with fluoride ion. Note that in this case the SEM group is removed considerably faster than the phenyl groups from the phosphate. ... 

The efficiency of this method was demonstrated by the elegant two-step synthesis of aspartame [87], Protection of the a-amino group and activation of the a-carboxylic group are accomplished in only one step Deprotection of the amino functionality occurs during aminolysis, such as with methyl phenylalaninate (H-Phe-OMe in equation 15)... 

M Meldal, B Klaus. Pentafluorophenyl esters for temporary carboxyl group protection in solid phase synthesis of A-linked glycopeptides. Tetrahedron Lett 48, 6987, 1990. 

Various AAs as such or their amidines react with triethylborane, triphe-nylborane, 9-borabicyclo[3.3.1]nonane (9-BBN), or with KBp3Ph to give the corresponding boroxazolidones 37. The reaction has synthetic utility for the simultaneous protection of the a-amino and a-carboxyl groups (83T2995 93JA11612). 

Several building blocks were prepared separately (Chart 7). Methyl frans-cinnamate gave by Sharpless enantiocontrolled dihydroxylation a diol from which by a series of stereo- and regioselective transformations (96) and Ru-catalyzed oxidation for transformation of the phenyl into a carboxyl group accompanied by adequate protection (97) and deprotection steps the protected OHAsp derivative 98 was obtained. 

Many different approaches have been developed for peptide synthesis, and it is not the intention to cover more than the basic principles here, with a suitable example. The philosophy to convert two amino acids into a dipeptide is to transform each difunctional amino acid into a monofunctional compound, one of which has the amino group protected, whilst the other has the carboxyl group protected. This allows... 

Evidence that Epoxycreatine is an Affinity Label. All the available evidence is consistent with the hypothesis that epoxycreatine behaves like an affinity label for the enzyme and that it is attacked by a carboxylate group of the enzyme. That is, it inactivated the enzyme rapidly at 0°C. Inactivation was complete and activity did not return upon exhaustive dialysis. Creatine was shown to give protection against the inactivation in the expected manner. Most importantly, though, the irreversible binding of the Inhibitor was shown to be stoichiometric using [ Cj-epoxycrea-tine that is, one and only one inhibitor molecule becomes bound per active site, even in the presence of excess inhibitor. 

Enantioselective acylation of amine and hydrolysis of amide are widely studied. These reactions are catalyzed by acylases, amidases and lipases. Some examples are shown in Figure 21.22 Aspartame, artificial sweetener, is synthesized by a protease, thermolysin (Figure 21(a)).22a In this reaction, the L-enantiomer of racemic phenylalanine methyl ester reacted specifically with the a-carboxyl group of N-protected L-aspartate. Both the separation of the enantiomers of the phenylalanine and the protection of the y-carboxyl group of the L-aspartate were unnecessary, which simplified the synthesis. 

Thus, according to Scheme 28, (-)-shikimic acid 169 was converted to cyclohexadiene derivative 170 via esterification of carboxyl group, protection of the m-disposed hydroxyls, and elimination of the remaining carbinol moiety. Catalytic dihydroxylation of 170 gave unsaturated esters 171 and 172 as a separable 1 1 mixture. The 5,5a-unsaturated isomer 171 was finally elaborated into the desired (-)-MK7607 (174) via simple protection-reduction-deprotection sequence. 

If du Vigneaud and Bodanszky had wanted a carboxylic-acid-protecting group that was more stable towards attack by nucleophiles, they could have made a t-butyl ester with isobutene in sulfuric acid. 

A Lilly group21"3 devised a synthesis of the bacterial cell wall precursor UDP-N-acetylmuramyl-pentapeptide (Park nucleotide) in which deprotection of a 2-(phenylsulfonyl)ethyl ester using a catalytic amount of DBU in dichloro-methane220,221 was an important step in the release of a carboxyl group [Scheme 6,99]. 2-(Methylsulfonyl)ethyl esters have also been cleaved under basic conditions to release a protected carboxylic acid. Scheme 6.100 shows an example from the closing stages of a synthesis of Surugatoxin.222... 

A panoply of protecting groups was enlisted in the synthesis of Damavaricin by Roush and co-workers.242 Here we show 2 steps [Scheme 8.100] towards the end of the synthesis in which a Teoc group and a 2-(trimethylsilyl)ethyl ester were cleaved simultaneously with TAS-F to liberate an amino group and a carboxyl group that served as partners in a macrolactamisation reaction. 

Like amino acids, PNA monomers have a carboxyl group and an amino group. Thus, they can be assembled into peptide chains like ordinary amino acids. Monomers with f-Boc or Fmoc protection on the amine are commercially available from, e.g.. Applied Biosystems, and the different considerations for PNA synthesis are well described (29). Steps and reagents not commonly used in peptide synthesis but important for PNA synthesis are as follows ... 

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