HMPB linker

PS-PEG-PAMAM[G3.0] dendronized support with HMPB-linker... 

Flbrsheimer, A. and Riniker, B. (1991) Solid-phase synthesis of peptides with the highly acid-sensitive HMPB linker, in Peptides 1990 Proceedings of the 21st European Peptide Symposium (Giralt, E. and Andreu, D. eds.), ESCOM, Lieden, pp. 131-133. 

Figure 4 (a) Analysis of dansyl-Ile-Thr(0 Bu -Pro-Gln-Trp-LysCBocFWang-linker-resin, giving peptide dansyl-Ile-Thr-Pro-Gln-Trp-Lys (MH+, 1006.0). The peak at 772.6 represents a small amount of undansylated material, (b) Analysis of Fmoc-Cys(Trt)-Lys(Boc)-Ile-HMPB-linker-resin, giving Fmoc-Cys-Lys-Ile (MH+, 585.5), Fmoc-Cys(Trt)-Lys-Ile (MH+, 849.8), and Fmoc-Cys-Lys-Ile disulfide [(M-S-S-M)H+, 1168.3], (c)Analysis of the disulfide of Fmoc-Cys-Asn-Cys-Lys(Boc)-Ile-FIMPB-linker-resin giving the disulfide of Fmoc-Cys-Asn-Cys-Lys-Ile (MH+, 801.0). (Reprinted from Ref. 64.)... 

For the solid-phase experiments [115], the commercially available Wang and HMPB-AM resins were chosen due their stability under the applied reaction conditions and an easy cleavage with TFA/DCM mixtures. Moreover, a novel, tailor-made and readily available linker, derived from inexpensive syringaldehyde was designed and proven to be superior to both standard Wang and HMPB-AM resins. For an initial study, as a proof of concept , the Wang linker was mimicked with a 4-methoxybenzyl group at N-1 position of a pyrazinone, and the sequence was evaluated in solution (Scheme 41). 

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. 

Figure 14.2 Ether and amide linked variants of some hydroxymethylphenoxy linkers. Wang (1) [8] HMPA (2) [9] Sasrin (3) [10] HMPB (4) [11].

A number of other useful highly acid-labile handles are also available. Most of these linkers are formed by introducing electron-donating substituents into the benzyl groups that serve as the peptide-resin anchor. The first handle of this type, 4-hydroxymethyl-3-methoxyphenoxyacetic acid (HMPA), 3, was introduced by Sheppard and Williams [22,23]. A closely related and more widely used alternative is 4-(4-hydroxymethyl-3-methoxyphenoxy) butyric acid [24-26] (HMPB), 4. 

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