Oximes solid-phase synthesis

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.

F. Polymer-bound Oximes in Solid-phase Synthesis. 182... 

The most widely used, and often most convenient reagents for such one-pot reactions are sodium hypochlorite (45) or hypobromite (16). These reactions are performed in the presence of an organic base (generally triethylamine) that normally enhances the yield of cycloaddition products (45). This method was employed for many intermolecular reactions (71) and also seems especially suited for intramolecular ones (72-77) as well as for the solid-phase synthesis (78) of 2-isoxazolines. Hypohalite can also be replaced by sodium broruite in combination with a catalytic amount of tri-u-butyltin chloride (79). In a related method, O-tributylstannyl oximes were treated with tert-butyl hypochlorite to produce nitrile oxides that were trapped with aUcenes or alkynes to afford the corresponding isoxazolines or isoxazoles in moderate to good yield (80). 

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. 

Scheme 3. Solid-phase synthesis of bromoacetylated peptide fragments containing either an oxime group (8, 10% overall yield) or a levulyl group (10, 14% overall yield).

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). 

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. 

WF DeGrado, ET Kaiser. Polymer-bound oxime esters as supports for solid-phase peptide synthesis. Preparation of protected fragments. J Org Chem 45, 1295, 1980. 

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

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

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