Kemp’s triacid

The hydrolysis of p-nitrophenyl acetate and bis(p-nitrophenyl phosphate) are frequently used to probe hydrolytic activity. A problem with some other dinuclear systems is that the Zn units are held together by bridging ligands which can be cleaved on reaction with the substrate.440 This is not the case in a ditopic ligand such as those designed by Lippard and co-workers based on Kemp s triacid imide with a xylyl spacer.441,442 Both zinc dimers and mixed metal dimers were formed and a structure characterized with a bridging phosphodiester (Figure 6). 

In 1990 Rebek reported an interesting self-replicating systems based on the Kemp s triacid derivative 82 (see Scheme 43) [112-114]. By a combination of hydrogen bonding and tt-tt stacking interactions, diamine 83 forms a binary complex with 82. In such a complex, the amine is ideally positioned to react with the activated ester in 82 yielding the ds-amide complex 84. 

Scheme 43 Rebek s self-replicating system based on Kemp s triacid derivative 82...

In 1989, Rebek and co-workers reported a simple system based on Kemp s triacid that served as a mimic of an enolizing enzyme [86]. This early mimic, however, had the enolizing substrate covalently attached to the triacid skeleton. In addition, the mimic did not possess any oxyanion hole functionalities. However, 2 years later the Rebek group reported a true enolizing catalyst that hosted a carboxylic acid as the oxyanion hole component (Scheme 4.8) [87]. The rate of enolization of the quinuclidone substrate was enhanced by a factor of 10 in the presence of 2.5 mM of the receptor (R = n-Pr). 

Amino acid binding by monolayers of long-chain derivatives of Kemp s triacid Ikeura Y, Kurihara K. Kunitake T (1991) J Am Chem Soc 113 7342... 

Solid-phase assembly of triple-helical peptides containing (Gly-Pro-Hyp)n sequences using, as a template, Kemp s triacid (KTA) is shown in Scheme 13.[56] Two synthetic routes are used to prepare template-assembled collagen-based structures composed of Gly-Pro-(iBu)Gly sequences. Both routes involve the attachment of the template derivative KTA-(Gly-OH)3 to the N-termini of peptide-peptoid chains. The first route is the solid-phase method as described for the (Gly-Pro-Hyp)n sequences. The second method is to cleave the peptide-peptoid chains from the resin and connect them to the template in soln. 

Scheme 2.8 Examples of ligands used to model the carboxylate coreofcarboxylate-bridged dinuclearironenzymes (a) R3XDK[for R = CH3 H2XDK = m-xylenediamine bis(Kemp s triacid) imide] [57] (b) differently substituted terphenyl-based ligands (e.g. for R1 = CH3, R2 = H TolArCOOH) [48].

Jeong, Kim et al. reported use of the chiral DMAP derivative 22e, which was synthesized from 3-amino-DMAP, Kemp s triacid, and N-acetyl-2,2 -diamino-l,l -binaphthyl [26], As summarized in Scheme 12.11, selectivity factors up to 21 were observed with 1 mol% modular catalyst 22e in the kinetic resolution of a variety of secondary alcohols with acetic anhydride in tert-amyl alcohol as solvent, conditions first described by Fu et al. [20]. 

Work by Rebek has resulted in the production of a versatile series of rigid clip hosts such a 6.48 6.50.32 These molecules are prepared readily from the conformationally rigid Kemp s triacid and various aromatic diamines (Scheme 6.6). The key feature of these hosts is the rigidity of the framework, which organises the materials into convergent C -shaped receptors. This rigidity is a consequence of... 

Scheme 6.6 Synthesis of Kemp s triacid derived molecular clips.

Explain the incorporation of the methyl substituents in the Kemp s triacid based molecular tweezers shown in Scheme 6.6 in terms of the principle of preorganisation discussed in Chapter 1. 

Several dinuclear Mn11 complexes based on the dinucleating L9 ligand [L9 = m-xylenediamine bis(Kemp s triacid imide)] have a (p.-carboxylato)2 core [lOOp] (Figure 18). 

Monotrifluoroacetylated diaminopyrazole was first reacted with the free Kemp s triacid to produce the imide, followed by N-Boc protection and amide-coupling with a m-substituted aniline derivative. Final Boc-deprotection occurred on the chromatography column leading directly to the new receptor modules. The recognition site X was chosen to be ethyl as a neutral reference, acetyl for polar side-chains, nitro for electron-rich aromatic residues and carboxylate for basic amino acids (Figure 2.4.4). 

Fig. 2.4.4. Synthesis of hosts 3-6 from Kemp s triacid and monotrifluoroacetylated diaminpyrazole 1 (a) 110 0C (b) B0C2O (c) m-substituted aniline derivative, PyCloP (d) silica gel. Right Productive conformation of the receptor modules found in Monte Carlo simulations (MacroModel 7.0).

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

Kocis P, Issakova O, Sepetov N, Lebl M, Kemp s triacid scaffolding for synthesis of combinatorial nonpeptide uncoded libraries, Tetrahedron Lett., 36 6623, 1996. 

Kemp s triacid 11 (cf. Scheme 4), a cyclohexane derivative in which... 

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