Paracyclophanes, macrocycles

Macrocyclic paracyclophanes were evaluated on inhibition of phosphatase Cdc25B. Compound 42 and 43 were found to be the most potent (IC50 values of 3.4 and 3.5 fiM, respectively) with greater than threefold selectivity over other phosphatases like PTPIB, PTPa, and PP2A (Figure 16.3). 

Macrocyclic polyethers containing the 2.2-paracyclophane unit are interesting structures and several such compounds have been prepared . Despite the diverse structural possibilities, the syntheses of these molecules have generally been accomplished by straightforward Williamson ether syntheses. The only unusual aspect of the syntheses appears to be a novel approach to certain paracyclophanes developed by Helgeson (see footnote 7a in Ref. 91). The first step of Eq. (3.28) illustrates the formation of the required tetrol, which is then treated with base (KOH or KO-t-Bu) and the appropriate diol dito-sylate to afford the macrocycle. 

Acid-promoted aquation of the binuclear complex Cu2L of the hexaaza macrocycle L = 2,5,8,17,20,23 -hexaaza[9.9]paracyclophane, whose half-life is of the order of a second, exhibits simple one-stage first-order kinetics. This is attributed to parallel reactions at each Cu(II) center having identical rate constants (305). The kinetics of dissociation of mono- and... 

Paracrystallinity, Cu/ZnO/AIjOj, 31 295 2"-Paracyclophanes, 32 453 Paracyclophanes, macrocycles, 29 206-208 Paraffin, see also Alkanes alkylation, 10 165, 27 98 carbon selectivity, bed residence time effects, 39 249-250 cracking, 39 283 cyclization, 28 295 rates, 28 301, 302 double cyclization, 28 312-314 in exhaust gases, 24 66, 67 hydrogenolysis, 30 43-44 hydroisomerization, 39 183 oxidation, 32 118-121 solubility enhanced hydrogeolysis, 39 285 Parahydrogen conversion rate correlations, 27 48-50... 

An enantioselective biomimetic synthesis of longithorone A was accomplished on the basis of proposed biosynthesis. " The syntheses of two [12]-paracyclophanes 105 and 107 are realized by applying ene-yne metatheses macrocyclization to 104 and 106, which are synthesized from the common substrate 103. Longtholone A is constructed using intermolecular and transannular Diels-Alder reactions followed by oxidation (Scheme 40). 

Both of the tetraaza[3.3.3.3]paracyclophane (1) and tetraaza[n.l.n.l]paracyclo-phane (n = 6, 7, 8 cf. 2) rings have frequently been used as fundamental molecular skeletons for preparation of functionalized macrocyclic hosts [24-36]. Formation of three-dimensionally extended hydrophobic cavities was approached by introducing multiple hydrocarbon branches into the macrocyclic skeletons. Multiple hydrophobic chains thus placed in a macrocycle must be extended in the same direction and undergo mutual association to attain their optimal hydrophobic interactions in aqueous media due to thermodynamic reasons, while in nonaqueous media they presumably assume a free and separated configuration to minimize their mutual steric interactions. Consequently, such hydrophobic branches may provide a large hydrophobic cavity in aqueous media. 

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. 

Diederich, F., Dick, K., New water soluble macrocycles of the paracyclophane type - aggregation behavior and host-guest-interaction with hydrophobic substrates. Tetrahedron Lett. 1982, 23, 3167-3170. 

A similar mixed ox a- thia macrocycle incorporating a rigid horseshoeshaped aromatic moiety, l,ll,21-trioxa-8,14-dithia[2,9,2]paracyclophane, L40, has been synthesized and reacted with copper iodide in MeCN solution (Scheme 19).160 Its polymeric copper iodide complex [Cu4I4(L40)2] 40 crystallizes, in a 2 1 metal to ligand ratio, as an ID infinite array of cubane-like units consisting of four copper atoms, four i3-iodine atoms, and four sulfur atoms, stemming from four different macrocycles. The Cu—Cu distances are about 2.731 A. Unfortunately, the photophysics of this compound have not been studied. 

M. Shair and co-workers were the first to apply the enyne metathesis for macrocyclization during the biomimetic synthesis of (-)-longithorone A." The two 16-membered paracyclophane building blocks, one diene and one dienophile component, were prepared using 50 mol% Grubbs s first-generation catalyst under 1 atm ethylene gas pressure. These components, after several additional steps, underwent two facile Diels-Alder cycloaddition reactions to afford the natural product. 

Thermal decomposition of dispiro[2.2.2.2]deca-4,9-diene, in the presence of conjugated dienes or styrenes, yielded [8]paracyclophanes, or [4.4]paracyclophanes, respectively. The paracyclophanes were formed when the fully ring-opened diradical intermediate from the dispiro compound was trapped by the alkenes in a macrocyclization process (see Section 2.4.1.5.2.8.). 

Synthesis of some sulfone-linked paracyclophanes from macrocyclic thioethers... 

Scheme 5 Synthesis of macrocyclic thioether sulfones and their oxidation to sulfone-linked paracyclophanes.

Peraza-paracyclophanes, 697, 698 Perazatetracyclohexano-crown-4 macrocycles, table. 651 Phenanthroline, 75, 87... 

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