Kemp s acid

Kemp s Acid Enzyme-Cleft and Self-Replication Models... 

Kemp s Acid Enzyme-Cleft and Self-Replication Models 347 5.2.1 Enzyme-Cleft Models with Convergent Functional Croups... 

J. Rebek, Jr., (1987) first developed a new synthesis of Kemp s acid and then extensively explored its application in model studies. The synthesis involves the straightforward hydrogenation (A. Steitz, 1968), esterification and methylation of inexpensive 1,3,5-benzenetricar-boxylic acid (trimesic acid 30/100 g). The methylation of the trimethyl ester with dimethyl sulfate, mediated by lithium diisopropylamide (V. J. Shiner, 1981), produced mainly the desired aff-cis-1,3,5-trimethyl isomer, which was saponified to give Kemp s acid. 

Heating Kemp s acid with appropriate aromatic diamines yields bis-imides with two convergently oriented carboxylic acid groups on the edges of a hydrophobic pocket. Dozens of interesting molecular complexes have been obtained from such compounds and can be traced in the Journal of the American Chemical Society under the authorship of J. Rebek, Jr., (1985 and later e.g. T. Tjivikua, 1990 B). 

Amino-5 -deoxy-2, 3 -0-isopropylideneadenosine was acylated at N-5 with an activated derivative of the 6-carboxy-2-naphthyl ester of Kemp s acid imide. The resulting molecule possesses self-complementary binding sites, the key feature of replicating molecules that act as templates for their own reproduction. The dimer of this molecule is, however, not very stable K = 630 L mol ). When the two initially mentioned educts are added, a small proportion of the ternary complex is also formed and undergoes a fast, template-catalysed... 

The a,p-unsaturated amides 180-188a have all been used in 1,3-dipolar cycloadditions with nitrile oxides, and some of them represent the most diastereoselective reactions of nitrile oxides. The camphor derivative 180 of Chen and co-workers (294), the sultam 181 of Oppolzer et al. (295), and the two Kemp s acid derived compounds 186 (296) and 187 (297) described by Curran et al. (296) are excellent partners for diastereoselective reactions with nitrile oxides, as very high diastereos-electivities have been observed for all of them. In particular, compound 186 gave, with few exceptions, complete diastereoselection in reactions with a wide range of different nitrile oxides. Good selectivities were also observed when using compounds 183 (298) and 184 (299-301) in nitrile oxide cycloadditions, and they have the advantage that they are more readily available. Curran and co-workers also studied the 1,3-dipolar cycloaddition of 187 with silyl nitronates. However, compared to the reactions of nitrile oxides, lower selectivities of up to 86% de were obtained (302). 

Julius Rebek and his group were also active at about the same time with enzyme-free self-replication of chemical structures. Unhke von Kiedrowski group, he did not use nucleotides, but a rephcator consisting of an adenosine derivative and a derivative of Kemp s acid (Rotello etal., 1991 Rebek, 1994). See also Figure 7.7 for a self-replicating system not based on nucleic-acid chemistry. There are several variations of this scheme, which are not illustrated here - for reviews see Sievers etal, 1994 Orgel, 1995. 

A variety of molecules with a functional group located in a cleft have been synthesized (a) Zimmerman SC, Zeng Z, Wu W, Reichert DE (1991) J Am Chem Soc 113 183 ( Molecular tweezers ) (b) Rebek Jr J, (1990) Angew Chem 102 261 Int Ed Engl 29 245 (Oefts based on derivatives of Kemp s acid ). In both classes, a functional group is located in a slot. But the shielding is only from the top and from the bottom, not from the sides. 

The synthesis of the active site analogue 206 that combines two essential features of the P450 enzymes has recently been accomplished (Fig. 34) [111]. The design involves the attachment of the thiophenolate ligand to the porphyrin 207 prepared very efficiently (> 80% yield) from the aldehyde 208 and the pyrromethane 209. Condensation of the free amine 210 with the acid chloride of Kemp s acid 211 furnished 206 containing a substrate binding site at the porphyrin face opposite to the thiolate ligand. Preliminary experiments with this... 

SCHEME 73. Catalytic cycle in the protonation of 2-isopropyl-5-methyl cyclohexanone lithium enolate using Kemp s acid imide derivative as a catalyst357,358... 

Convergent carboxylic acids of long-chain derivatives of Kemps s acid 7 are useful receptors for fitting nitrogen heterocycles, e.g. benzimidazole and is one of very few examples for the selective binding of electroneutral molecules in water. 

Bach and coworkers reported a new strategy to achieve enantioselective photoreactions in solution based on the use of a chiral host derived from Kemp s acid [134-138]. They designed and synthesized a hydrogen bonding chiral template with a lactam functionality 60, which can bind prochiral amide substrates through two hydrogen bonds in an enantioface-selective fashion with the aid of a bulky group fixed in the 1,3-axial position, as illustrated in Scheme 22. 

Asymmetric induction (See also Enantioselective) chiral ketones, 62, 106-107 chiral sulfoxides, 8-9 steroid synthesis, 27, 278-281 Asymmetric syntheses. See Enantioselective. .. Asymmetry of vesicle membranes, 351 dATP. See 2 -Deoxynucleoside 5 -triphosphates Atropisomers binap chelands, 102-103 Kemp s acid arylimides, 347 porphyrin oligomers, 348—349 5,10,15,20-tetraarylporphyrins, 253 Axial/equatorial stereoselectivity ... 

KAPA. See 1,3-Propanediamine, mono-K salt Katsuki-Sharpless oxn. See Sharpless epoxidation Kekulene = 15,23 16,22-dimethenobenzofl, 2-a 5,4-a ]dipentaphene, 338 Kemp s acid, 346-347... 

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