Trityl chloride resin

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

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). 

C1 Trityl Chloride resin (17.33 g, NovaBiochem, Lot A20915, 200 - 400 mesh, 1 % DVB, 1.33 mmol / g, 23.0 mmol) was placed in a 500-mL round-bottom flask. /V,/V-Dimcthylformamide (200 mL) was added, which caused the resin to swell this suspension was gently stirred by a magnetic stir bar. Propargyl amine (10 g,... 

The solid-phase synthesis strategy was based on the utilization of 4-methoxy-trityl chloride resin. To gain access to a large number of compounds, only commercially available building blocks were used and protective groups were omitted if possible. The synthesis strategy resulted in a new class of cationic lipids as shown in Figure 5 (compound 6). The structure bases on... 

In 1997, Bauer and colleagues described the preparation of a hydroxylamine resin 183 using trityl chloride resin 182 as the base matrix as well as its application to the synthesis of various hydroxamic acids (Scheme 81). 

A-Hydroxyphthalimide 178 was used as a source of the hydroxylamine reacting with trityl chloride resin 182 in the presence of triethylamine to obtain the A-hydroxyphth-alimide derivative 183. This intermediate is transformed to the desired hydroxylamine resin 184 by treatment with hydrazine. The peptidic and peptidomimetic hydroxamic acids 185 and 186 were synthesized using the described solid-supported reagent (Scheme 82). 

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]. 

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). 

The high regioselectivity of reactions of the salts 231 with various electrophilic agents was demonstrated by alkylation of 5-(3-chloropropyl)-l //-tctrazolc 250 with trityl chloride resin in the presence of Et3N. The corresponding resin containing the Nz-isomer 251 was obtained (Equation 39) <2000JC019>. 

Trityl-based resins are highly acid-labile. The steric hindrance of the linker prevents diketopiperazine formation and the resins are recommended for Pro and Gly C-terminal peptides. Extremely mild acidolysis conditions enable the cleavage of protected peptide segments from the resin. These resins are commercially available as their chloride or alcohol precursors. The trityl chloride resin is extremely moisture-sensitive, so reagents and glassware should be carefully dried before use to avoid hydrolysis into the alcohol form. It is necessary to activate the trityl alcohol precursor and it is highly recommended to reactivate the chloride just before use see Note 4). After activation, attachment of the first residue occurs by reaction with the Fmoc amino acid derivative in the presence of a base. This reaction does not involve an activated species, so it is free from epimerization. Special precautions should be taken for Cys and His residues that are particularly sensitive to epimerization during activation (Table 2). 

Coupling of 4-(4-hydroxymethyl-3-methoxyphenoxy)-butyric acid (HMPB, for synthesis of peptide acids) or p-[(R S)-a-[l- (9H- fluorenyl- methoxyform-amido]- 2,4- dimethoxybenzyl] - phenoxyacetic acid (modified Rink linker, for synthesis of carboxamide peptides) linkers to MBHA resin For Fmoc chemistry several types of solid supports are available, which include hydroxymethyl-based, aminomethyl-based, and trityl chloride resins. We describe the use of the MBHA resin. In this case the respective linker (to achieve peptide acid or amide) is coupled to the resin and first amino acid is then coupled to the linker. Attachment of the linker to the resin is a reaction between the carboxyl-group of the linker and amino-group of the MBHA resin. Commercially available resins with linkers already attached could also be used. 

Fig. 17.19 Synthesis of rosamine library on solid support, (a) K2C03, Cu, DMF, 130°C (b) H2S04, 80°C (c) modification for R1 (d) SnCl2, EtOH, 90°C (e) 2-chloro-trityl chloride resin, pyr, CH2C12/DMF (f) R2 Grignard reagent, THF, 62°C (g) 1 %TFA, CH2C12...

A special case is the binding of maleimides onto Tr resins (151) [260]. The latter were used efficiently in Diels-Alder and [2 -1- 3]-heterodipolar additions [261]. By anchoring maleimide to a trityl chloride resin through its silver salt [260], Barrett and co-workers [261] were able, after performing a one-pot synthesis by combining the preformed free base of the amino ester, the aldehyde, the dehydrating agent, the Lewis acid and the base in the presence of the solid-supported maleimide, to obtain the desired cycloadduct product (157). In this way, they were able to produce a 120-member library (Scheme 32). 

Place 1 g of 4-methoxyltrityl chloride resin (for attachment through the His or Cys side chain) or trityl chloride resin (for Lys or Ser) in a round-bottomed flask and swell it using the minimum amount of DCM for 5 min. 

Related Reagents. Polymer-bound diphenyl chlorosilane, trityl chloride resin Merrifield resin. 

Another example for a multidetachable linker system is the sulfamate linker 587 used by Ciobanu and Poirier to develop a-substituted estradiol sulfamate and phenol libraries [316]. The linker was synthesized via the attachment of a sulfamate group (bearing steroidic compounds) to trityl chloride resin. After modification of the steroids on solid supports, the target molecules... 

Ciobanu and Poirier (Scheme 3.42). This synthesis made use of a multifunctional sulfamate linker unit, prepared by loading steroidal sulfamates 234 onto simple trityl chloride resin 182. After solid-phase modifications (coupling with amino acids and carboxylic acids to introduce two levels of molecular diversity), cleavage with piperazine (10 equiv) at 45°C cleaved the sulfur-oxygen bond providing the phenols... 

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