Polymeric benzyl esters

The solid-phase synthesis of glycopeptides was first realized by applying the polymeric benzyl ester principle of Merrifield. According to this methodology, Lavielle and associates (50) used 7V-(tm-butyloxycarbonyl)-<9-glycosyl serine derivative 153 for condensation with resin-linked alanine 154. 

Because O-glycosylation can also be accomplished with active esters (e.g., penta-fluorophenyl esters) [11] of Fmoc serine and threonine, the Fmoc technique provides a general method for the synthesis of glycopeptides. Thomsen-Friedenreich antigen glycopeptides and neoglycoproteins have been obtained by this method in preparative amounts [12], In combination with acid-labile polymeric benzyl ester anchors, this Fmoc technique was applied to solid-phase syntheses of glycopeptides [11,13,14]. 

The catalytic hydrogenolysis of benzyl esters — a well known and clean procedure in conventional peptide chemistry — recently was applied successfully to peptide cleavage from polystyrene supports [216]. The hydrogenation of the polymeric benzyl ester anchor bonds was performed in the presence of palladium II acetate with hydrogen at 60 psi,... 

Patchomik and Kraus (1970), Kraus and Patchomik (1971a,b), and Szabo et al. (1977) employed a polymeric benzylic ester for immobilizing an acid, whereas Camps et al. (1971) used the esters of 2-hydroxyethylpolystyrene. The latter polymer was prepared by... 

By carrying out the Dieckmann condensation using a polymeric benzyl ester, Crowley and Rapoport (1976) demonstrated the advantage of a purification effect in solid-phase synthesis in addition to hyperentropic efficacy. The Dieckmann cyclization of a nonpolymeric benzylic ester produces a mixture of two soluble keto esters whose separation by some conventional method becomes necessary (a rather difficult separation). 

In the first solid phase peptide syntheses chloromethylated PS (1 Scheme 1) was converted to the polymeric benzyl ester of an N-protected amino acid. More elaborate attachments are used now. 

In a related approach, Padovani et al. prepared copolymers of styrene and a styrene derivative containing two pendant ester bonds using free-radical polymerization (Scheme 15) [108], Transesterification reactions were conducted with Novozym 435 as the catalyst and benzyl alcohol or (rac)-l-phenylethanol as the nucleophile. Interestingly, the ester bond closest to the polymer backbone (position A in Scheme 15) remained unaffected, whereas ester bond B reacted in up to 98% to the corresponding benzyl ester. The transesterification was not only highly chemoselective but also enantioselective. Conversion of (rac)-l-phenylethanol in the transesterification reaction amounted to a maximum conversion of 47.9% of the (/ )-alcohol, and only at the ester position B. 

Since the benzyl esters are found to be a suitable functional group for connecting two polymer skeletons, the next problem is to connect two equivalent polymer skeletons with benzyl esters. This can be achieved by applying recently developed living radical polymerization [21-23]. 

There are two strategies for constructing a polymer with benzyl ester in the middle of the skeleton. One is to make polymer skeletons with the same molecular weight, and then combine two skeletons with benzyl ester. The other is to synthesize a chemical with propagation sites of polymerization at both sides of benzyl ester, and use the chemical as an initiator of living polymerization. Since the former strategy did not work well, probably due to low reactivity of polymer molecules with benzyl esters, the latter approach will be mentioned. 

Hyper-branched polymers are prepared in a single-step polymerization from ABX monomers. Thus, a perfectly branched structure is present in dendrimers, whereas irregular branching is present in hyper-branched polymers. Aluminum alkoxide-based initiators or tin-based catalysts have been successfully used for the preparation of, hyper-branched [160-162, 166-168], dendrimer-like star polymers [160], and star-shaped polymers. The first and second generations of the benzyl ester of 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) are effective initiators for the ROP of lactones (e-CL) in the presence of Sn(Oct)2. The... 

In this chapter, we describe the isomerization, dimerization, and topochemical polymerization of benzyl muconates with various kinds of substituents on the benzyl ester group (Scheme 24.1), in order to reveal the solid-state reaction mechanism by the direct observation of crystal structures which change during the reactions. 

Additives such as HOBt or DMAP can be used while attached to a polymer. Thus, the polymeric //-benzyl-1-hydroxybenzotriazole-6-sulfona-mide (19) [47] and the polymeric 1-hydroxybenzotriazole (20) [48] have been shown to be highly efficient for the solution synthesis of amides. The efficiency of 19 could be attributed to its high acidity, conferred by the sulfonyl moiety. The procedure for amide construction involves the formation of an activated ester on the derivatized polymer followed, in a second step, by treatment with an amine to generate the amide in solution. This HOBt-supported polymer has also been applied for the preparation of N-hydroxysuccinimide esters, useful for the modification of proteins [49]. Polymeric DMAP is a less basic compound and generally gives very low racemization [50]. 

DF 0.09, 10% cross-linked gel polystyrene, the enolate generated with triphenyl-methylUthium at room temperature and trapped as soon as the red color of Ae base faded, gave 94-97% GC yields from acylation with p-nitrobenzoyl chloride or acetyl chloride and from alkylation with 1-bromobutane or benzyl bromide. Isolated yields were 73-87% on a 16-34 mmol scale, and 77% in one example on a 100 mmol scale (175 g of dry polymeric reagent). TTie polymer was recycled with no decrease in acylation yield. The analogous benzyl ester in solution gave 59% self[Pg.273]

The asymmetric selectivity arises from the preferential formation of (S)-elective center at the beginning followed by the formation of (R)-elective center after the consumption of most of the (S)-monomer. The copolymerization of the (RS)-mono-mer and methyl methacrylate by this complex yielded a highly isotactic copolymer in which the (S>monomer predominantly incorporated over the (R)-monomer. On the other hand, in the copolymerization with a,a-dimethylbenzyl methacrylate only the homopolymer of a-methylbenzyl methacrylate was obtained with the same as-i mmetric selectivity as in the homopolymerization of this monomer. The results indicate that the steric interaction between the methyl group at the a- rosition of benzyl ester and the (-)-sparteine moiety of the catalyst plays an important role in the stereoelection of the polymerization. 

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