Kaiser resin

A very interesting approach to the solid-supported synthesis of hydroxamic acids was developed by Golebiowski and Klopfenstein . It employs an oxime resin (Kaiser resin) 171d and, unlike all previouxsly reported methods, allows the use of acid-labile protecting... 

Among the electrophilic handles proposed for head-to-tail and side-chain-to-tail cyclization of peptides on solid support by intrachain aminolysis with concurrent detachment of the product from the resin in the protected form (see Section 6.8.3.1.3), generally the oxime resin (also called Kaiser resin)1364 365 and a thioester resin[363l are recommended (see Scheme 14). In addition to the classical head-to-tail cyclization,[3431 the oxime resin is used for side-chain cyclizations as well as for the synthesis of multicyclic peptides vide infra). Due to its dual functions, the oxime resin can be employed only with Boc/Bzl chemistry it is not compatible with Fmoc/tBu chemistry where the basic N -deprotection leads to free amino groups and thus to premature cyclization reactions. To avoid this premature cleavage of the... 

These handles and functionalized solid supports can only be used for the Boc/Bzl strategy. The conditions necessary for Fmoc group removal would lead to a premature release of the peptide from the resin. The most widely used systems of this kind are oxime-based (Kaiser) resin (Section 4.3.1.2.2.3.1) and handles that incorporate the fluorenylmethyl moiety. 

Cleavage of Peptides from Oxime-Based (Kaiser) Resins General Procedurerf ... 

Fig. 3.8 Variations to solid phase synthesis of polyamides. Use of Fmoc monomers on jS-Ala-Wang resin (left) provides polyamides containing a jS-alanine residue near the C-ter-mini. Polyamides synthesized on the Kaiser...

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>. 

JC Hendrix, JT Jarrett, ST Anisfield, PT Lansbury. Studies related to a convergent fragment-coupling approach to peptide synthesis using the Kaiser oxime resin. J Org Chem 57, 3414, 1992. 

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

Five novel RGD peptides 81 containing either one or twice furanoid SAAs 80 were recently synthesized via an efficient solid-phase strategy based on Kaiser s oxime resin 71d (Scheme 43). 

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

Generally, monitoring of the cyclization reaction on resin is recommended it is readily performed by the qualitative Kaiseb376 test and/or more correctly by HPLC/MS upon cleavage/deprotection of aliquots from the resin. In this context, attention must be paid to the false positive Kaiser test as resulting from the piperidyl amide formation.1366369375 ... 

Fmoc-Rink-Nle-pMeBHA-resin (1 g, 0.55 mmol g ) was swollen for 1.5 h in NMP in a reaction vessel equipped with a sintered glass bottom, and placed on a shaker. The Fmoc group was removed with 20% piperidine in NMP (8mL, 2 x 15 min) and after washing with NMP (8mL, 5 x 2 min), the Fmoc removal was monitored by the ninhydrin Kaiser test. Coupling of building blocks such as iV -Fmoc-/Va>-carb-oxyalkyl(OAl)Xaa-OH or /V -Fmoc-/V" -aminoalkyl(Aloc)Xaa-OH, or N -alkylated amino acids such as... 

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>. ... 

The MBHA resin (substitution 0.63 mmol-g 1) was acylated in CH2C12 with the Boc N-protected linker 15 (2 equiv) in the presence of BOP as coupling agent and DIPEA as base. After 4 h and classical washings, the coupling was controlled by Kaiser s test. The protected resin 16 was ready for classical solid-phase synthesis. 

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