Aromatic linker

De Clercq s group did not observe any inhibition of syncytium formation by the biscyclam containing an aliphatic linker (3), but observed it in the case of the biscyclam containing an aromatic linker (30), albeit at... 

Aliphatic substrates also perform well, forming five membered rings in good yield and high enantioselectivity Eq. 6a. Typical Michael acceptors, however, are not sufficiently electrophilic to induce cyclization to form six-membered aliphatic rings. In order to effect this cyclization, use of a more electrophilic Michael acceptor, such as alkylidene malonate 83, was required Eq. 6b [70]. The difference in reactivity is presumably due to the extra conformational freedom of the aliphatic linker compared to the fused aromatic linker of substrate 79 coupled with potential competing non-productive pathways. 

Bridger, G. J., Skerlj, R. T., Thornton, D., Padmanabhan, S., Martelluci, S. A, Henson, G. W., Abrams, M. J., Yamamoto, N., De Vreese, K., Pauwels, R., De Clercq, E. Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on die aromatic linker, J. Med. Chem. 38 (1995), 366 — 378. 

Joon et al. (282) recently reported the synthesis of a 10-member array of 3-aminoimi-dazoline-2,4-diones L24 (Eig. 8.48) using MeO-PEG-amine soluble support, the aromatic linker 8.98, and the monomer sets Mi (six a-amino acid isocyanates) (283) and M2 (four aza a-amino acids) (247). The linker was coupled to the support via an amide bond (step a, Eig. 8.48), and deprotection of the phenolic hydroxyl (step b) gave supported 8.99. Coupling with monomer set Mi (step c) and removal of the butyl ester (step b) produced 8.100, which was coupled to monomer set M2 (step d) and deprotected (step b) to give 8.101. Each deprotection step was followed by precipita-... 

Iqbal and coworkers have reported another approach to cycUc di- and tripeptide mimics constrained with a disubstituted aromatic linker which exploits a free-radical-mediated macrocycHzation [8]. As an example, the tripeptide derivative 8 was promoted to undergo 7-endo ring closure under tin hydride conditions, providing the cyclic peptide 9 in 54% yield (Scheme 5). The reasonable yields obtained for these macrocycHzation processes is proposed by the authors to occur because of preorganization of the acycHc precursors, possibly owing to a reverse turn (y/ turn). 

In 1990, Osuka, Maruyama, Mataga, and coworkers examined porphyrin dyad 4 and other molecules closely related to dyad 3 with different aromatic linkers joining the macrocycles [19], When the zinc porphyrin of 4 was excited in dimethylforma-mide solution, Pzn-PFe(m) was produced. It decayed with a time constant of 52 ps, and the Pzn -PFe ii) state was observed by transient absorption techniques. The charge-shifted state decayed in 1.6 ns. By studying photoinduced electron transfer in the entire series of molecules with different linkages, the dependence of rate constant on the separation of the porphyrins was determined. A value for f in Eq. 2 of 0.4A- was obtained. 

A linker containing a 2,4-bis(4-carboxyphenoxy)-6-methoxy-S-triazine amide group was introduced into a oligonucleotide using reagent 207. However, an aliphatic non-nucleotide linker was found to be more effective than an aromatic linker derived from 207, in stabilising oligonucleotides triplexes. ... 

From the systematic investigation of the Park and Jew group, several highly efficient and practical polymeric cinchona PTCs were developed (Scheme 6.6). Interestingly, polymeric catalysts with a specific direction of attachment between aromatic linkers (e.g., benzene or naphthalene) and each cinchona unit were found to be effective in the asymmetric alkylation of 4b. The phenyl-based polymeric PTCs with the meta-relationship between cinchona units such as 14, 15, and 18 showed their high catalytic efficiencies. Furthermore, the 2,7-dimethylnaphthalene moiety as in 16 and 17 was ultimately found to be the ideal spacer for dimeric cinchona PTC for this asymmetric alkylation. For example, with 5 mol% of 16, the benzylation of 4b was completed within a short reaction time of 30 min at 0 ° C, affording (S)-5a in 95% yield with 97% ee. Almost optically pure (>99% ee) (S)-5a was obtained at lower reaction temperature (—40 °C) with 16, and moreover, even with a smaller quantity (1 mol%), its high catalytic efficiency in terms of both reactivity and enantioselectivity was well conserved. 

A few other variations are included here to demonstrate the diversity of this class with regard to molecular shape. Vogtle et al. s multiple ansa compound (115, R = CH2CH2OCH2CH3), an unexpected product obtained from an attempt to synthesize biscalixarenes with aromatic linkers, has two bridges threaded through the macrocycle formed by joining the two calixarenes subunits [152]. Siegel et al. s... 

The lactam-bridged and hydrocarbon-stapled helices feature flexible crosslinks. Entropic considerations would suggest that rigid linkers might afford more stable helices. Two groups have recently studied the effect of linker flexibility on helix stability. Woolley and coworkers found that a rigid aromatic linker that matches the distance between the i and (+11 side-chains provides much greater stability... 

The LihD Cooidination Aliphatic Linkers / 153 The LihD Cooidination Aromatic Linkers / 163 Heterometalhc ([Pg.144]

Table II includes a representative sampling of a number of Ln-MOFs and CPs built from aromatic linker molecules. Note that this class of materials is dominated by the benzene-carboxylate (and related) species as shown in Fig. 16. This is an attractive linker for a number of reasons, including its planarity and rigidity that to a first assumption, may suggest a more restricted structural diversity when compared to (e.g.) the aliphatics. Despite these features, however, no less rich coordination chemistry or resultant topologies in this family are seen.

In Dash s work [46], they combined the aromatic linker and cellulose nanowhiskers to synthesize a novel delivery system for amine containing biologically active compounds and drug... 

Sharpless observed that the choice of the particular cinchona-derived chiral ligand can invert the regioselectivity in the reaction with styrenes [96-98], Janda [96, 97] proposed that this effect might be due to steric reasons and aryl-aryl interactions [99,100] of the olefin with the aromatic linker of the ligand. Moreover, it was shown that substituents on the aromatic ring of the styrene can influence the stereoselectivity [101], which prompted Ojima [102] to propose a relation between the regioselectivity and the dipole moment of the aromatic group of the olefin. 

Recently, Lim et al. [42] reported the synthesis of a new class of 1,3,5-triazine-based microporous polymers by Friedel-Crafts reaction of 2,4,6-trichloro-l,3,5-tri-azine with aromatic compounds (Fig. 5.7). The surface areas of the polymers are in the range of 558-1,266 m g , depending on the aromatic linker length. At ambient pressure and temperature, the polymers exhibit high CO2 uptakes of 38-51 cm g . The isosteric heats determined at low loading were 36 kJ mol for polymers 2 and 3 and 33 kJ mol for polymer 4, which were comparable to those of functionalized MOPs [39]. Polymers 2 and 3 showed a higher heat of adsorption than polymer... 

Later 1,2,4-oxadiazoles have been used mainly as bioisosteric replacements of esters and amides (1994JMC2421, 1999JMC4331), and only recently have they been introduced as an essential part of a pharmacophore. In general, 1,2,4-oxadiazoles are flat, aromatic linkers able to give a bending to a drug s structure, and also exert an electron-withdrawing efiect. 

Fig. 11 (a) Resonance fonns of bis(phenalenyls) with different aromatic linkers (b) crystal structure of 38d [37] (c) the RVB model fOT the eleetronie structure of 38e [38]... 

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