Active ester polymer-supported

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information for 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... 

A polymer-supported sulfonamide, prepared from an amino acid activated ester and a polystyrene-sulfonamide, is stable to acidic hydrolysis (CF3COOH HBr/ HOAc). It is cleaved by the safety-catch method shown below. ... 

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. 

A polymer-supported sulfonamide, prepared from an amino acid activated ester... 

Lithium ester enolate addition to imines has been used for the construction of optically active p-lactams, e.g. 64 and the lithium enolates have been found to be superior to other metal derivatives for both yields and diastereoselectivity in some cases <00H(53)1479>. Immobilized lithium ester enolates have been utilized for the first time <00OL907> and soluble polymer supported imines were used to obtain N-unsubstituted azetidin-2-ones under mild conditions <00CEJ193>. Both lithium and titanium enolates have been employed to obtain cholesterol absorption inhibitors <99TA4841>. Lithium ynolates 65 add to imines to provide P-lactams in good to excellent yield <00TL5943>. 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

For further elongation of the peptide chain, successive coupling reactions with other polymeric active esters may be carried out until the desired sequence is obtained. The polymeric active esters are prepared by the attachment of the N-protected amino acids or peptides to a suitable insoluble polymer. Potentially useful polymeric supports in this case should carry a free hydroxyl function to which the carboxyl group of the amino acid derivatives may be coupled. Crosslinked poly(4-hydroxy-3-... 

Caddick [19] has reported the use of a novel polymer-supported tetra-fluorophenol-Unked acrylate as an activated acceptor for intermolecular radical reactions. Treatment of immobiUzed acrylate 132 with a variety of alkyl iodides in the presence of tributyltin hydride and AIBN gave the corresponding esters 133 (Scheme 29). NucleophiUc cleavage using amines gave amides 134 in good overall yield whilst regenerating phenol resin 131. 

Another field of application for active esters is solid-phase synthesis. Some polymer-supported reagents are available commercially (see Fig. 9). The acid is first immobilized on a polymer support as an active ester and the excess reagents are washed away conveniently. Finally, the amide is released by amine treatment. During the cleavage, a limited amount of amine can be used to avoid the presence of excess amine in the final mixture. The acid is loaded onto the resin using classic ester condensation methods for TFP resin 35 (66), HOBt resin 36 (67), and oxime resin 37 (68). In the case of the triazine resin 38, the acid is loaded via an aromatic nucleophilic substitution in the presence of a base (69). 

Stannic chloride has been attached to monomers 21 containing ester (21a), carbazole (21b), pyrrolidone (21c), nitrile (21d) and pyridine (21d) moieties. The polymeric ligands were prepared by copolymerization of styrene, divinylbenzene and functional monomers such as methyl methacrylate, A -vinylcarbazole, Af-vinylpyrrolidone, acrylonitrile and 4-vinylpyridine [33], These polymers were treated with stannic chloride in chloroform to afford the corresponding polymer-supported stannic chloride complexes (Eq. 8). These polymeric complexes have been used as catalysts for such organic reactions including esterification, acetalization, and ketal formation. These complexes had good catalytic activity in the reactions and could be reused many times without loss of activity. Their stability was much better than that of plain polystyrene-stannic chloride complex catalyst. 

There are in general two ways to synthesize side chain polymers, polymerization of peptide-functional monomers or introduction of the peptide moiety afterwards, by grafting. The latter technique is based on the synthesis of polymers containing some form of functionality in the side chain, normally an activated ester moiety, which can further react with a peptide. The most commonly used method for the polymerization of monomers containing active esters is free radical polymerization. In particular many activated acrylate esters have been polymerized in this manner [12] (Table 1) for use in a wide variety of applications, from the preparation of polymer drug conjugates [13,14] to supports for solid phase peptide synthesis [15,16]. 

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