2-Chlorotrityl resin

Chloromethyl resin Wang resin 2-Chlorotrityl resin Rink amide resin Kaiser oxime resin TentaGel S RAM... 

Hydroxyethylene resin HMPA resin Chloromethyl resin Hydroxymethyl resin Tritylchloride resin Rink amide resin Wang resin REM resin Aminomethyl resin Chloromethyl resin Wang resin Rink amide resin PAL amide resin MBHA resin Chloromethyl resin Chlorotrityl resin Wang resin PAM resin Polystyrene resin Chloromethyl resin Chlorotrityl resin Wang resin Rink amide resin Sasrin resin Polystyrene resin Chloromethyl resin Benzoic acid resin Wang resin Trityl resin 2-Chlorotrityl resin PAL resin Rink amide resin MBHA resin REM resin Hydroxymethyl resin Polystyrene Aminomethyl resin Chloromethyl resin 2-Chlorotrityl resin Hydroxyethyl resin Rink amide resin Wang resin MBHA resin Sieber resin... 

Fig. 7 Kinetics of microwave-assisted loading of 2-chlorotrityl chloride resin with Fmoc-isoleucine at 110 °C. For comparison, the dashed line indicates the level of loading after 1 h at room temperature...

Investigation of the microwave-assisted attachment of Fmoc-protected amino acids onto 2-chlorotrityl chloride resin indicated higher loadings and increased rates compared to standard room temperature procedures [146]. In this comparative study standard procedures yielded 0.37 mmol/g loading after 1 hour, whereas at 110 °C using microwave dielectric heating, a similar result (0.38 mmol/g) was obtained after only 15 min (Fig. 7). 

Hydroxamic acids are an important class of compounds targeted as potential therapeutic agents. A-Fmoc-aminooxy-2-chlorotrityl polystyrene resin 61 allowed the synthesis and subsequent cleavage under mild conditions of both peptidyl and small molecule hydroxamic acids (Fig. 14) [70]. An alternative hydroxylamine linkage 62 was prepared from trityl chloride resin and tV-hydroxyphthalimide followed by treatment with hydrazine at room temperature (Scheme 30) [71]. A series of hydroxamic acids were prepared by the addition of substituted succinic anhydrides to the resin followed by coupling with a variety of amines, and cleavage with HCOOH-THF(l 3). 

Mellor SL, McGuire C, Chan WC. lV-Fmoc-aminooxy-2-chlorotrityl polystyrene resin A facile solid-phase methodology for the synthesis of hydroxamic acids. Tetrahedron Lett 1997 38 3311-3314. 

Y-FMOC-AMINOOXY-2-CHLOROTRITYL POLYSTYRENE RESIN FOR HIGH THROUGHPUT SYNTHESIS OF HYDROXAMIC ACIDS... 

N-Fmoc-aminooxy-2-chlorotrityl polystyrene (212 mg, 0.95 mmol g 1,0.2 mmol) was placed in a reaction column (1.0 cm diameter alternatively, an appropriate reaction vessel can be used, e.g., Quest 210 synthesizer 5-mL reaction vessel) and preswollen in DCM DMF (1 1, 3mL) for 24 h (note 4). The resin was then washed with DMF (10min, 2.5 mL min-1) and Fmoc-depro-tected by treatment with 20% v/v piperidine in DMF (10 min, 2.5mL min-1). The resin was then washed with DMF (lOmin, 2.5 mL min ), after which excess DMF was removed. 

V-(9-Fluorcnylmethoxycarbonyl)aminooxy-2-chlorotrityl polystyrene was then N-deprotected within minutes by treatment with 20% v/v piperidine in DMF to afford the key intermediate aminooxy-2-chlorotrityl polystyrene. With this in hand, N-acylation was then carried out and, where appropriate, followed by a series of chemical transformations to yield resin-bound... 

An alternative to the above is esterification by reaction of the salt of the Fmoc-amino acid with the halomethylphenyl-support (see Section 3.17). It was established in the 1960s that this method of esterifying A-alkoxycarbonylamino acids, which does not involve electrophilic activation, is not accompanied by enan-tiomerization. Examples of supports with haloalkyl linkers are bromomethylphe-noxymethyl-polystyrene and 2-chlorotrityl chloride resin (see Section 5.23). 

CHLOROTRITYL CHLORIDE RESIN FOR SYNTHESIS USING FMOC/TBU CHEMISTRY... 

FIGURE 5.22 (A) Reaction of an Fmoc-amino acid with 2-chlorotrityl chloride resin.56 The ester bond formed is cleavable by the mild acid, which does not affect tert-butyl-based protectors. (B) Generation of a protected peptide containing cystine by detachment of a chain, deprotection of cysteine residues, and oxidation of the sulfhydryls by the reagent containing iodine. The cations produced are trapped by CF3CH2OH. 

K Barlos, O Chatzi, D Gatos, G Stavropoulus. 2-Chlorotrityl chloride resin. Studies on anchoring of Fmoc-amino acids and peptide cleavage. Int J Pept Prot Res 37,513,... 

K Barlos, D Gatos, S Kutsogianni, G Papaphotiou, C Poulus, T Tsegenidis. Solid phase synthesis of partially protected and free peptides containing disulphide bonds by simultaneous cysteine oxidation-release from 2-chlorotrityl resin. Int J Pept Prot Res 38, 562, 1991. 

Y Fujiwara, K Akaji, Y Kiso. Racemization-free synthesis of C-terminal cysteine-peptide using 2-chlorotrityl resin. Chem Pharm Bull (Jpn) 42, 724, 1994. 

Scheme 16 Synthesis of Sulfated Peptides with Tyrosine 0-Sulfate Synthons on 2-Chlorotrityl Resin as Proposed by Kitagawa1 581...

The mild acidolytic cleavage procedure noted above is used to deprotect various side chain protected peptides synthesized in solution or on chlorotrityl-resin with tyrosine O-sulfate synthons as listed in Table 4. The overall yields are significantly superior to those obtained by postsynthetic sulfation of the purified peptides, since they are typical for synthetic peptides after the final deprotection and purification step. The additional main advantage of this approach derives from a facile analytical characterization, since sulfonated byproducts at the tyrosine and tryptophan level, as well as oxidation of the methionine residues resulting from postsynthetic sulfation of tyrosine peptides are avoided. 

The leading solid phases are the 2-chlorotrityl chloride resins. Professor K. Barlos (University of Patras, Greece) has made the single most important contribntion to the development of these resins. They consist of a polystyrene-base resin crosslinked with a small amonnt of divinylbenzene and functionalized with 2-chlorotritiyl chloride. 

Mellor, S. L. McGuire, C. Chan, W. C. M-Fmoc-Aminooxy-2-Chlorotrityl Polystyrene Resin A Facile Solid-Phase Methodology for the Synthesis of Hydroxamic Acids, Tetrahedron Lett. 1997, 38, 3311. 

Seebach and co-workers 383 have demonstrated that the coupling of (3-amino acids can be achieved in a solid-phase protocol with the use of Fmoc-protected (3-amino acids 58 linked to a chlorotrityl resin (Scheme 18). They demonstrated that while 33-amino acids can be coupled in a straightforward manner, the analogous 32-amino acids are a little more problematic, with HPLC analysis of the products showing some impurities. 

Attachment of carboxylic acids to supports as trityl esters is achieved by treatment of the corresponding trityl chloride resin with the acid in the presence of an excess of a tertiary amine (Figure 3.5 see also Section 13.4.2). This esterification usually proceeds more quickly than the acylation of benzyl alcohol linkers. Less racemization is generally observed during the esterification of A-protected a-amino acids with trityl linkers than with benzyl alcohol linkers [47], If valuable acids are to be linked to insoluble supports, quantitative esterification can be accomplished by using excess 2-chlorotrityl chloride resin, followed by displacement of the remaining chloride with methanol [64]. 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

Histidine and histamine derivatives, as well as other imidazoles, have been successfully immobilized by N-tritylation of the imidazole ring with trityl chloride resin [534] (Entry 2, Table 3.29 see also Section 15.8) or with 2-chlorotrityl chloride resin [535-537]. Histidine can also be linked to insoluble supports as the N-dinitrophenyl deriva-... 

Only a few examples have been reported of the etherification of alcohols with resin-bound diarylmethyl alcohols (Entry 5, Table 3.30 Entry 5, Table 3.31 [564]). Diarylmethyl ethers do not seem to offer advantages over the more readily accessible trityl ethers, which are widely used as linkers for both phenols and aliphatic alcohols. Attachment of alcohols to trityl linkers is usually effected by treating trityl chloride resin or 2-chlorotrityl chloride resin with the alcohol in the presence of a base (phenols pyridine/THF, 50 °C [565] or DIPEA/DCM [566] aliphatic alcohols pyridine, 20-70 °C, 3 h-5 d [567-572] or collidine, Bu4NI, DCM, 20 °C, 65 h [81]). Aliphatic or aromatic alcohols can be attached as ethers to the same type of light-sensitive linker as used for carboxylic acids (Section 3.1.3). 

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