Dimethoxybenzyl amide

The trivial name bisnorisopenicillin has been coined for the 6-acylamino-3-thia-l-a2abicyclo[3.2.0]heptane-2-carboxylic acid (85) structural class. While not extensively investigated, an example of this class has been prepared as shown in Scheme 66 (78JMC413). The following features of this sequence are noteworthy (a) the exclusively cis cycloaddition to form intermediate (86) and (b) the use of the 2,4-dimethoxybenzyl amide blocking group. 

The related 3,4-dimethoxybenzyl group has been cleaved from an amide with Na/NH3, 82% yield. ... 

Amide nitrogens can be protected by 4-methoxy or 2,4-dimethoxyphenyl groups. The protecting group can be removed by oxidation with ceric ammonium nitrate.243 2,4-Dimethoxybenzyl groups can be removed using anhydrous trifluoroacetic acid.244... 

An alternative procedure for the synthesis of aliphatic 2-substituted oxazoline hydroxamates was described by Pirrung and colleagues in the context of preparing inhibitors of E. coli LpxC zinc amidase [378], As shown in Scheme 6.210 a, the protocol involved the cyclization of suitable amides, formed in situ by acylation of a serine-derived 0-2,4-dimethoxybenzyl (DMB)-protected hydroxamate. The cyclization... 

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. 

Protection of glutamine and aspan ine. The 2,4-dimethoxybenzyl group (Dmb) has been recommended for protection of the amide groups of asparagine and glutamine residues in peptide synthesis. The derivatives are nicely crystalline, and the Dmb group can be removed by trifluoroacetic acid or anhydrous hydrogen fluoride. 

The dimethoxybenzyl group was used for backbone protection of the pseudopeptides of the form Xaa /(CH2N)Gly (Xaa = amino acid). It is introduced by reductive alkylation with the aldehyde and NaCNBHs. Acidolysis with TFMSA in TFA/thio-anisole is used to remove it from the amine, but the efficiency is dependent upon the peptide sequence. Cleavage of the Dmb group is also achieved by conversion with trifiuoroacetic anhydride to the amide, which is then removed with NaBFLt/EtOH (93-97% yield). It may also be cleaved with TsOH. ... 

A/-[(Ethoxycarbonyl)methyl]-p-menthane-3-carboxamide (No. 1776) is hydrolysed in pancreatic juice and rat liver homogenate, but the major route is ester hydrolysis rather than amide hydrolysis (Poet et al., 2005). With A/-(heptan-4-yl)benzo[d][1,3]dioxole-5-carboxamide (No. 1767), there was rapid metabolism in the presence of rat hepatocytes, but no amide hydrolysis products were found. A similar result was found with A/1 -(2,4-dimethoxybenzyl)-AC-(2-(pyridin-2-yl)ethyl)-oxalamide (No. 1768) rapid metabolism in the presence of rat hepatocytes was observed, and no amide hydrolysis products were found (Denning et al., 2004a). 

Glycopeptide 31 was synthesized in a custom-made, fully automatic continuous-flow peptide synthesizer constructed essentially as described elsewhere (19). A resin consisting of a cross-linked polystyrene backbone grafted with poly(ethylene glycol) chains (TentaGel , Rapp Polymer, Germany) and functionalized with the Rink amide linker (p-[a-(fluoren-9-ylmethoxyformamido)-2,4-dimethoxybenzyl]phenoxyacetic acid, Nova-biochem, Switzerland) was used for the syntheses. DMF was distilled before use. 

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