74725-77-2Relevant academic research and scientific papers
The cubane paradigm in bioactive molecule discovery: Further scope, limitations and the cyclooctatetraene complement
Houston, Sevan D.,Fahrenhorst-Jones, Tyler,Xing, Hui,Chalmers, Benjamin A.,Sykes, Melissa L.,Stok, Jeanette E.,Farfan Soto, Clementina,Burns, Jed M.,Bernhardt, Paul V.,De Voss, James J.,Boyle, Glen M.,Smith, Maree T.,Tsanaktsidis, John,Savage, G. Paul,Avery, Vicky M.,Williams, Craig M.
supporting information, p. 6790 - 6798 (2019/07/22)
The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.
Thermochemical properties of iodinated cubane derivatives
Griffiths, Justin R.,Tsanaktsidis, John,Savage, G. Paul,Priefer, Ronny
experimental part, p. 15 - 20 (2010/04/25)
Since the initial synthesis of cubane, numerous derivatives have been made with a diverse range of physical, chemical, and biological properties. Some iodinated cubane derivatives have been reported to be thermolytically unstable and/or rearrange in situ. An iodinated cubane-containing, norbornene-based polymer showed rapid thermo-decomposition during TGA studies. Bis-(4-iodocubylmethyl)-dialkoxy disulfide undergoes fragmentation more easily than its non-iodinated counterpart. The synthesis and thermal behaviour of a library of iodinated cubane compounds are herein reported. Most of the iodinated cubane derivatives showed melting/decomposition with no exotherm upon cooling. 4-Iodo-1-vinylcubane was observed to rearrange to 4-vinyl-trans-β-iodostyrene and its cyclooctatetraene intermediate during DSC analysis. TGA studies on 1-iodo-4-(hydroxymethyl)-cubane suggest that this particular iodinated cubane scaffold is mostly prone to rapid thermo-decomposition.
Halogenation of cubane under phase-transfer conditions: Single and double C - H-bond substitution with conservation of the cage structure
Fokin,Lauenstein,Gunchenko,Schreiner
, p. 1842 - 1847 (2007/10/03)
The first highly selective C - H chlorination, bromination, and iodination of cubane (1) utilizing polyhalomethanes as halogen sources under phase-transfer (PT) conditions is described. Isomeric dihalocubanes with all possible combinations of chlorine, bromine, and iodine in ortho, meta, and para positions were also prepared by this method; m-dihalo products form preferentially. Ab initio and density functional theory (DFT) computations were used to rationalize the pronounced differences in the reactions of 1 with halogen (Hal·) vs carbon-centered trihalomethyl (Hal3C·) radicals (Hal = Cl, Br), For Hal3C radicals the C - H abstraction pathway is less unfavorable (ΔG?298 = 21.6 kcal/mol for C3C· and 19.4 kcal/mol for Br3C· at B3LYP/6-311+G**//B3LYP/6-31G**) than the fragmentation of the cubane skeleton via SH2-attack on one of the carbon atoms of 1 (ΔG?298 = 33.8 and 35.1 kcal/mol, respectively). In stark contrast, the reaction of 1 with halogen atoms preferentially follows the fragmentation pathway (ΔG?298 = 2.1 and 7.5 kcal/mol) and C - H abstraction is more unfavorable (ΔG?298 = 4.6 and 12.0 kcal/mol). Our computational results nicely agree with the behavior of 1 under PT halogenation conditions (where Hal3C· is involved in the activation step) and under free-radical photohalogenation with Hal2 (Della E. W., et al. J. Am. Chem. Soc. 1992, 114, 10730). The incorporation of a second halogen atom preferentially in the meta position of halocubanes demonstrates the control of the regioselectivity by molecular orbital symmetry.
Initiation and bonding of diamond and other thin films
-
, (2008/06/13)
A method for initiating and bonding thin films on substrates is described. The method employs an interlayer comprising a self-assembling monolayer (SAM). The SAM is formed from monomers, one end of which are capable of bonding to the substrate, and the other end of which form a surface similar to, and capable of initiating the formation of a film. Additionally, compositions for monomers, methods for SAM formation, and methods for film formation are disclosed. In a preferred embodiment the thin film is comprised of diamond.
Alkynylcubanes as precursors of rigid-rod molecules and alkynylcyclooctatetraenes
Eaton, Philip E.,Galoppini, Elena,Gilardi, Richard
, p. 7588 - 7596 (2007/10/02)
We have developed new methodology for the synthesis of alkynylcubanes and have used these compounds to make rigid-rod molecules constructed of cubane and acetylene subunits. Terminal and substituted alkynylcubanes 7a, 7b, 8a, 8b, 12a, and 12b were synthes
Synthesis of Bridgehead Fluorides by Fluorodeiodination
Della, Ernest W.,Head, Nicholas J.
, p. 2850 - 2855 (2007/10/02)
Fluorodeiodination is found to be an attractive procedure for the synthesis of bridgehead fluorides.Thus, treatment of the corresponding iodide with xenon difluoride in dichloromethane at ambient temperature generally leads to high yields of the fluoride.Evidence suggests the intermediacy of the bridgehead cation in this reaction, and accordingly the substrates which are unfavorable disposed to fluorodeiodination are the bicycloalkyl iodides.In this context the isolation of a small quantity of methyl 4-fluorobicyclohexane-1-carboxylate (46, R= COOMe) is significant because it represents the first occasion on which the elusive 1-bicyclohexyl cation has been trapped.We have also demonstrated that synthesis of the iodides themselves can be accomplished efficiently both by Barton halodecarboxylation and by treatment of the carboxylic acid with lead tetraacetate and iodine.
SYNTHESIS OF IODOCUBANES BY DECARBOXYLATIVE IODINATION
Tsanaktsidis, John,Eaton, Philip E.
, p. 6967 - 6968 (2007/10/02)
An efficient method is described for the preparation of iodocubanes from the corresponding carboxylic acids utilizing thiohydroxamic ester methodology with 2,2,2-trifluoroiodoethane as the iodide source.
