Syntheses of naturally occurring cytotoxic [7.7]paracyclophanes, (−)-cylindrocyclophane A and its enantiomer, and implications for biological activity

Yamakoshi, Hiroyuki; Ikarashi, Fumiya; Minami, Masataka; Shibuya, Masabumi; Sugahara, Tsutomu; Kanoh, Naoki; Ohori, Hisatsugu; Shibata, Hiroyuki; Iwabuchi, Yoshiharu

doi:10.1039/b909646a

Cited by 31 publications

(24 citation statements)

References 39 publications

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“…Merocyclophanes A and B ( 1 and 2 ) possessed similar levels of antiproliferative activity as those reported for cylindrocyclophanes A–F against various cell lines (0.5 – 5 µg/mL). A SAR study on cyclindrocyclophane A suggested that the 2,5-dialkylresorcinol moiety was the pharmacophore needed for the antiproliferative activity of cylindrocyclophanes, and that the activity was significantly enhanced by the presence of [7.7]paracyclophane core structure (Yamakoshi et al, 2009). The structure of merocyclophane A ( 1 ) differs from that of cyclindrocyclophane A by the position of methyl groups and the lack of alkyl hydroxy groups; however, both compounds showed a similar level of activity.…”

Section: Resultsmentioning

confidence: 99%

Merocyclophanes A and B, antiproliferative cyclophanes from the cultured terrestrial Cyanobacterium Nostoc sp.

et al. 2012

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The cell extract of a cultured terrestrial Nostoc sp. (UIC 10062), obtained from a sample collected at Grand Mere State Park in Michigan, displayed antiproliferative activity against the HT-29 human colon cancer cell line. Bioactivity-guided fractionation of the cell extract, combined with LC-MS analysis, led to the isolation of two cyclophanes, named merocyclophanes A and B (1 and 2). Their structures were determined by various spectroscopic techniques including HRESIMS, and 1D and 2D NMR analyses. The stereoconfiguration was assigned on the basis of X-ray crystallographic and CD analyses. The structures of merocyclophanes A and B (1 and 2) established a hitherto unknown [7.7]paracyclophane skeleton in nature, as characterized by α-branched methyls at C-1/14. Merocyclophanes A and B (1 and 2) displayed antiproliferative activity against the HT-29 human colon cancer cell line with IC50 values of 3.3 and 1.7 µM, respectively.

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Section: Resultsmentioning

confidence: 99%

Merocyclophanes A and B, antiproliferative cyclophanes from the cultured terrestrial Cyanobacterium Nostoc sp.

et al. 2012

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“…It was speculated that this highly gratifying result was a consequence of the reversible nature of the RCM reaction and the low‐energy nature of 258 a – b . Indeed, it was subsequently shown that trienes ( E )‐ 259 and ( Z )‐ 259 (precursors to head‐to‐head [8.6]cyclophanes) also afforded cylindrocyclophane F ( 27 b ) in 75–81 % yield!148 The cross‐metathesis/RCM reaction was recently repeated by other researchers in a synthesis of cylindrocyclophane F and its enantiomer 149…”

Section: Ring‐closing Metathesismentioning

confidence: 99%

Olefination Reactions in the Synthesis of Cyclophanes

Bodwell

Nandaluru

2012

Israel Journal of Chemistry

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A survey of olefination reactions that have been used in the synthesis of cyclophanes is presented. This covers the Ramberg-Bäcklund reaction, the Wittig and related reactions, the McMurry and related reactions, ring-closing metathesis (alkenes, alkynes and ene-ynes), aldol condensations and Siegrist reactions, as well as miscellaneous reactions. The McMurry reaction and ring-closing metathesis have enjoyed the greatest popularity in recent years, but they are typically used for complementary purposes. In virtually all cases, the McMurry reaction is used to install a twocarbon (1,2-ethenylene) bridge, whereas ring-closing metathesis is used to construct bridges that are at least fourmembered, but usually considerably longer. Some wellknown olefinations have seen little or no use in the field of cyclophane chemistry.The Ramberg-Bäcklund reaction [9] is the final step in a two-to three-step thioether-to-alkene conversion. As such, it appears to be well-suited for the synthesis of alkene-containing cyclophanes. Even though it applies to pre-existing cyclophanes, it warrants attention in the context of this review because both bonds of the newly formed alkene are generated during the reaction. Within the broader scope of organic synthesis, the Ramberg-Bäcklund reaction has been exploited frequently to introduce a double bond into large rings, [10] small rings [11] and more exotic ring systems such as cyclic enediynes. [12] However, it has not performed well in the synthesis of cyclophanes.The first cyclophanes to be synthesized using the Ramberg-Bäcklund reaction were the isomeric biphenylophanes (Z,Z)-7 and (E,E)-7 (Scheme 3). [13] As expected from mechanistic considerations, [14] they were formed stereospecifically in good yield (both 65 %) from the diastereomeric sulfones meso-6 and (AE)-6, respectively. Interestingly, the report of these very good results came shortly after Boekelheide wrote that "the Ramberg-Bäcklund reaction is unsatisfactory when applied to 2,11-dithia-[3.3]cyclophanes". [15] Prior to Boekelheides comment on the Ramberg-Bäcklund reaction, Martel reported that a Ramberg-Prof. Graham Bodwell obtained his B.Sc. and M.Sc. from the University of Victoria, Canada, working with Prof. Reginald Mitchell on cyclophanes. He then moved to Braunschweig, Germany, where he joined the group of Prof. Dr. Henning Hopf as a "Doktorand". Cyclophanes were also the focus of his doctoral research. He then took a break from cyclophanes and worked in the field of asymmetric synthesis as a post-doctoral fellow with Prof. Steve Davies at Oxford University. He then accepted a faculty position at Memorial University, where he now holds the rank of Professor. Cyclophanes have always been one of his core research interests.Penchal Reddy Nandaluru obtained his B.Sc. and M.Sc. from Sri Venkateswara University, India, and then worked as a chemist with AVRA Laboratories in India before joining the group of Prof. Graham Bodwell at Memorial University in St. John's, NL, Canada. The main theme of his doctoral research is the appli...

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“…The anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate derivatives (Mehellou et al, 2009) Potential anti-cancer compounds have been reported including a poly-THF spiroketalcontaining compound which is active against both breast and ovarian cancer cell lines (Piccialli et al, 2009). Both enantiomers of (-)-cylindrocyclophane were synthesised and found to have very similar activities against the human colon cancer HCT-116 cells (Yamakoshi et al, 2009). Iron(III)-salen complexes were used to demonstrate that, somewhat surprisingly, the less DNA cleavage activity these compounds showed in vitro, the more efficient they were at inducing apoptosis in MCF7 cells (Ansari et al, 2009).…”

Section: Bioactivesmentioning

confidence: 99%