Protecting groups polymer esters

The first, and still widely used, polymer-supported ester is formed from an amino acid and a chloromethylated copolymer of styrene-divinylbenzene. Originally it was cleaved by basic hydrolysis (2 N NaOH, FtOH, 25°, 1 h). Subsequently, it has been cleaved by hydrogenolysis (H2/Pd-C, DMF, 40°, 60 psi, 24 h, 71% yield), and by HF, which concurrently removes many amine protective groups. Monoesterification of a symmetrical dicarboxylic acid chloride can be effected by reaction with a hydroxymethyl copolymer of styrene-divinylbenzene to give an ester a mono salt of a diacid was converted into a dibenzyl polymer. ... 

The protective group is removed by mildly alkaline conditions that do not cleave methyl or benzyl esters. The group is stable to CF3COOH, HCl-AcOH, and HBr-AcOH. A polymer-bound version of this group has also been developed. ... 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

In order to test the influence of the C-terminus protecting groups on the properties of the resulting polymer, the ethyl, hexyl, and palmityl esters of N-benzyloxycarbonyl-L-tyrosyl-L-tyrosine were synthesized and the corresponding polymers (poly(CTTE),... 

Ester formation is the main and most efficient means of protecting carboxylic acids. The protection of a carboxylic acid as an amide is infrequent, as its removal normally requires drastic conditions. Most of the work concerned with the use of light-sensitive protecting-groups for carboxylic acids is in peptide synthesis. Carboxylic acids are protected as photosensitive esters, including ester linkages to polymer supports or as (difficult to prepare) photosensitive amides. Many of these techniques may be readily applied to sugar acids. 

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

Although several routes have been published for the preparation of hydroxamic acids on solid phase, these generally involve the preparation of a special linker to which hydrox-ylamine is attached. Dankwardt s approach obviates the need for special linkers or protecting groups, by displacing the desired hydroxamic acid from the resin directly using hydroxylamine, as illustrated in Scheme 86. CarboxyUc-acid-ester-linked, polymer-supported, Cbz-protected amino acids 195 (formed from 194) were displaced from the resin with aqueous hydroxylamine to provide the corresponding hydroxamic acids 196. 

Unsaturated tetrahydropyran derivatives have received only cursory attention in the literature as heterocyclic monomers. 2,3-Dihydropyran and several of its substituted derivatives apparently undergo cationic polymerization in a manner typical of vinyl ethers (72MI11103), while tetrahydropyranyl esters of methacrylic acid (123) are fairly typical free radically polymerizable monomers (Scheme 35) (74MI11105). The THP group was used in this study as a protecting group for the acid functionality, and it was found that deprotection of polymers (124) could be accomplished under extremely mild conditions. 

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