Resins, solid-phase oxime synthesis

Scheme 11 Synthesis of a Lanthionine Peptide via Solid-Phase Peptide Synthesis and Final Cleavage from Kaiser Oxime Resin 481...

Belitsky, J.M., D. H. Nguyen, N. R. WuRTZ, and P. B. Dervan. Solid-phase synthesis of DNA binding polyamides on oxime resin. Bioorg. Med. Chem. 2002,... 

Scialdone MA, Shuey SW, Soper P, Hamuro Y, Bums DM. Phosgenated p-nitrophenyl(polystyrene)ketoxime or phoxime resin. A new resin for the solid-phase synthesis of ureas via thermolytic cleavage of oxime-carbamates. J Org Chem 1998 63 4802-4807. 

Depending on the reaction temperature and reaction time, tetrahydroisoquinoline 357 afforded different mixtures of 1,2,3,4,11,11 a-hcxahydro-6//-pyrazino[ 1,2-3]isoquinolines 358-361 and tetracyclic compound 362 (Scheme 30) <2005JA16796>. Each of the individual diastereoisomers 358-361 could be transformed into the compound 362. z7r-3//,4a//-3-Phcnylpcrhydropyra/ino[ 1,2-7]isoquinoline-l,4-dione was prepared via automated parallel solid-phase synthesis on Kaiser oxime resin <1998BML2369>. l,2,3,5,6,7-Hexahydropyrido[l,2,3-r/f ]quinoxaline-2,5-dionc was obtained by catalytic hydrogenation of ethyl 3-(2-oxo-l,2,3,4-tetrahydro-5-quinoxalinyl)acrylate in the presence of TsOH over 5% Pd/C catalyst under 40 psi of hydrogen <1996JME4654>. 

RB Scarr, MA Findeis. Improved synthesis and aminoacylation of p-nitrobenzophe-none oxime polystyrene resin for solid-phase synthesis of protected peptides. Pept Res 3, 238, 1990. 

Scheme 22 Solid-phase synthesis of the biotinylated, farnesylated tetrapeptide (59) using the Kaiser benzophenone oxime resin.

Due to the vast numbers and rapidity of novel developments in solid-phase synthesis over the past ten years, a number of reports currently found in the literature deal with solid-phase syntheses of lanthionine peptides. There are at least two different approaches to synthesize lanthionine peptides in which the sulfide bond links amino acid halves that are not direct neighbors within the peptide chain (Scheme 10). One obvious approach, method A, is based on the coupling of a preformed, orthogonally protected lanthionine monomer to the N-terminus of a peptide oxime resin. 48 This is then followed by acid-catalyzed cyclization and simultaneous release from the resin during amide bond formation with the C-terminal carboxy group via the peptide cyclization method on oxime resin (see Section 6.73.2.2). The alternative approach is lanthionine formation after peptide synthesis from amino acid derivatives, such as serine and cysteine (method B). 

A high yielding synthesis of anthranil from 2-nitrobenZaldehyde makes use of zinc and allyl bromide as the reducing agent. The method has also been used for the preparation of 3-substituted anthranils from 2-nitrophenyl ketones <99H(51)1921>. A solid phase synthesis of 3-aminobenzisoxazoles 15 is based on the displacement of fluoride from 2-fluorobenzonitriles by the Kaiser oxime resin and subsequent hydrolysis of the C=N bond <99JOC4547>. A synthesis of 3-(2-dialkylaminoethyl)benzisoxazoles from oximes of 2-hydroxyphenyl ketones has also been described <99H(51)2139>. ... 

On the other hand, pyrenyl-L-alanine 184 has also been used as a conformational probe in the characterization of an artificial 4-a-helix bundle protein.11,121 The 53-residue peptide 186 incorporating one residue of 184 in each of two different helical segments was synthesized by solid-phase synthesis using a segment condensation strategy and the oxime resin. Boc-pyrenyl-L-alanine 191 was coupled just like any other amino acid by the BOP/HOBt method in DMF. CD and fluorescence studies demonstrated that the two pyrene groups were in close proximity forming an excimer complex, which is possible only when the polypeptide chain folds into a 4-a-helix bundle structure. 

Another field of application for active esters is solid-phase synthesis. Some polymer-supported reagents are available commercially (see Fig. 9). The acid is first immobilized on a polymer support as an active ester and the excess reagents are washed away conveniently. Finally, the amide is released by amine treatment. During the cleavage, a limited amount of amine can be used to avoid the presence of excess amine in the final mixture. The acid is loaded onto the resin using classic ester condensation methods for TFP resin 35 (66), HOBt resin 36 (67), and oxime resin 37 (68). In the case of the triazine resin 38, the acid is loaded via an aromatic nucleophilic substitution in the presence of a base (69). 

The synthesis of a series of isoxazoles 15 and isoxazolines 15a on the solid phase has been reported by Pei and Moos [50] via [3 + 2] cycloaddition of alkenes and alkynes with highly reactive nitrile oxides. The cycloaddition reactions of resin-bound peptoids were carried out in toluene at 100°C or in DCM-H2O at room temperature, depending on the precursors of the nitrile oxides. Benzaldehyde oxime and various nitroalkyl compounds were selected as nitrile oxide precursors. The nitrile oxides were generated in situ by reacting the nitroalkyl compounds with phenyl isocyanate and triethylam-ine or by oxidizing the oximes with sodium hypochlorite in the presence of triethylamine (Fig. 7). 

Fin 1989 Findeis, M.A. and Kaiser, E.T., Nitrobenzophenone Oxime Based Resins for the Solid-Phase Synthesis of Protected Peptide Segments, J. Org. Chem., 54 (1989) 3478-3482. 

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