Trityl resins 2-chlorotrityl chloride

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). 

Two trityl-based supports are presently in common use for the production of peptide adds by Fmoc SPPS 2-chlorotrityl chloride resin 7 (12) and 4-(chloro(diphenyl)methyl)benzoyl resin 8 (13). 

These resins are extremely moisture sensitive, and so it is essential that all reagents and glassware should be dried thoroughly before use. 2-Chlorotrityl chloride resin can be stored desiccated at room temperature 4-(chloro-(diphenyl)methyl)benzoyl resins should be generated from the precursor trityl alcohol immediately before use as described in Protocol 5. The chemical characteristics of 7 and 8 are identical. 

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). 

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