Caged-type cyclophanes

Cage-Type Cyclophanes Embedded in Synthetic Bilayer... 

Fig. 3A-C. Space-filling models of artificial receptors, each being capable of providing a large hydrophobic cavity A octopus cyclophane 4 B steroid cyclophane 6 C cage-type cyclophane 8...

In order to construct a hydrophobic three-dimensional cavity that is in-tramolecularly limited in space, we have prepared cage-type cyclophanes by linking macrocyclic rings. First we prepared a macropolycyclic host, which is constructed with two rigid macrocyclic skeletons of different size, tetraaza[3.3.3.3]paracyclophane as the larger one and tetraazacyclotetradecane as the smaller one, and four flexible hydrocarbon chains that connect the two macrocycles [40]. The flexibility of four hydrocarbon chains connecting the two macrocycles allows the induced-fit host-guest interaction in aqueous media. 

Fig.4. DSC thermograms for aqueous dispersions of peptide lipid 9 (1.0x 10 moldm ) in aqueous phosphate buffer (10 mmol dm ) at pH 7.0 A in the absence of cyclophane B in the presence of cage-type cyclophane 7 (5.0 x 10 mol dm C in the presence of cage-type cyclophane 8 (5.0 X 10 mol dm )...

Fig. 5A-C. Gel-filtration chromatograms on a column (column size, 10 mm (I.D.) x 200 mm flow rate, 2.0 cm min ) of Sephadex G-50 with aqueous phosphate buffer (10 mmol dm ) at pH 7.0 as eluent A cage-type cyclophane 8 alone (1.0 x 10" mol) B hybrid assembly formed with 7 (1.0 X 10" mol) and 9 (2.0 x 10" mol) C hybrid assembly formed with 8 (1.0 x 10" mol) and 9 (2.0 X 10" mol)...

Fig. 10. Schematic representation of guest-binding behavior of hybrid assemblies formed with peptide lipid 9 and cage-type cyclophanes 7 and 8, indicating conformational change of the host cavity...

The cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

Murakami et al. have reported binding studies on (4Z, 15Z)-bilirubin IXa and pamoic acid with a water-soluble, chiral, cage-type cyclophane (Figure 78)... 

The cage-type peptide cyclophanes (7 and 8) exhibit discrimination toward steroid hormones, as effected by hydrophobic and n-n interactions. In addition, the chirality-based discrimination between a- and -estradiol as well as between D- and L-amino acids bearing an aromatic moiety is performed on the basis of their capacity of forming efficient hydrogen bonding with the host molecules in aqueous media [41, 43]. 

Furthermore, a cage-type peptide cyclophane bearing D-valine residues in place of L-valine moieties shows a CD band at 244 nm with of —1.1 x 10 in HEPES buffer at 30.0 °C. It becomes apparent that the four pyridinium moieties bound to the chiral o-valine residues are similarly twisted in the same direction, but the twisted direction of bridging components in the host is opposite to that evaluated for the host bearing L-valine residues. A similar asymmetric character... 

Homeomorphs of the two-point bicycle show up in an interesting collection of structures, ranging from the simple cage-type bicyclophane (73) [93, 94] to the extended homeomorphs by Lehn et al. [95], Vogtle et al. [96], and Moore et al. [97]. Other molecular representations are Moore and Bedard s flat molecular turnstile (74) [98], Hart and Vinod s cuppedophanes (75) [99-102], and Okazaki et al. s bowl-shaped bicyclic cyclophane (76) [103,104]. 

Wennerstrom and coworkers have synthesized numerous cage-type derivatives [33]. In 1982 they reported the synthesis of bicyclophanes 77-80, and showed that the cyclophanes were conformationally mobile such that twisted, helical conformations could be achieved, and, in most cases, were even favored. 

Timmermans et al. report that diastereoselectivity can be induced in the intramoleuclar meta photocycloaddition of ethenes to the benzene ring as a result of minimisation of steric interactions between substituents on the linking tether of the bichromophore and a methoxy group at the 2-position of the arene unity this type of photoprocess has also been used as a key step in a formal synthesis of crinipellin B (Wender and Dore). New polycyclic cage compounds 43 have been obtained by irradiation of the [3.3,3] (1,3,5) cyclophane 44 (Sakamoto et al.) and Kubo et al. have described the intramolecular [3 + 2] photocycloaddition of bichromophores such as 45 which gives rise to nine- to eleven-membered ring systems 46. 

The Mannich-type condensation of various primary phosphines with formaldehyde and primary aromatic diamines with spatially divided amine groups allowed to obtain several types of cage PJ4-containing cyclophanes 209-210 with two l,5-diaza-3,7-diphosphacyclooctane fragments in the basic framework (Scheme 12.71) [173-179]. The spacers of the starting diamines were formed by... 

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