Alkoxybenzyl alcohol resins

Wang SS. p-Alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonylhy-drazide resin for solid-phase synthesis of protected peptide fragments. J Am Chem Soc 1973 95 1328-1333. 

P Sieber. An improved method for anchoring of 9-fluorenylmethoxycarbonyl-amino acids to 4-alkoxybenzyl alcohol resins. Tetrahedron Lett 28, 6147, 1987. 

Wang, S.-S. p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycar-bonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments, J. Am. Chem. Soc. 1973, 95, 1328-1333. 

Mergler, M. Nyfeler, R. Tanner, R. Gosteli, J. Grogg, P. Peptide Synthesis by a Combination of Solid-Phase and Solution Methods. 11. Synthesis of Fully Protected Peptide Fragments on 2-Methoxy-4-alkoxybenzyl Alcohol Resin, Tetrahedron Lett. 1988, 29,4009. 

Peptide hydrazides are readily obtained by hydrazinolysis of suitably protected peptides linked to the resin via a benzyl ester.Alternative to the hydroxymethyl ester linkage of the Merrifield resins, l-methyl-2-oxo-phenylethyl ester,2-nitrobenzyl ester O or 4-meth-oxybenzyl ester type linkages are also utilized.b - Recently, fuUy protected hydrazides were obtained in good yields on 2-methoxy-4-alkoxybenzyl alcohol resin (Sasrin ) by hydrazinolysis with 20% anhydrous hydrazine in DMF using DMA as solvent the reaction was significantly slower, but with less side products. 

To 4-alkoxybenzyl alcohol resin (100 mg, 0.45 mmol g, prewashed with CHjCb) in CH2CI2 (2mL) was added at 0 °C Emoc-Val-OH (4 equiv), B0C2O (4 equiv), Py (14 pL), and DMAP (2 mg). The mixture was gently stirred at 0°C under anhydrous conditions for 16 h. Then the resin was washed with DME (3x3 mL) and CHjCb (3x3 mL) and the substitution determined by cleavage of the Emoc group and absorbance measurement at 301 nm of the dibenzofulvene-piperidine adduct. Optical purity of the resin-bound amino acid was determined by the Marfey method. The 5deld of the derivatization of the 4-alkoxybenzyl alcohol resin was 86% and the content of D-amino add 0.3%. 

For the Fmoc/tBu approach, several handles and resins are available for the synthesis of free peptide acids. Among the most conunonly used are the Trt(2-Cl)-Cl resin 2, the 4-alkoxybenzyl alcohol resin (Wang resin, 7),P 1 and the 4-(hydroxymethyl)phenoxyacetic acid (HMPAA, and 3-[4-(hydroxymethyl)phenoxy]propanoic acid (HMPPA, 9)1 han-... 

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