Facile Unmasking of Dicobalt Hexacarbonyl Complexes of 1-Cyclodecene-3,9-diynes (Enediynes)

Jones, Graham B.; Wright, Justin M.; Rush, Teresa M.; Plourde, Gary W.; Kelton, Thomas F.; Mathews, Jude E.; Huber, A.; Davidson, James P.

doi:10.1021/jo9716035

Cited by 50 publications

(24 citation statements)

References 12 publications

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“…Allyltrimethylsilane, usually the nucleophile of choice for probing Ferrier rearrangements leading to C ‐glycosylation, was chosen to test the reactivity of cobalt‐complexed alkynylglycal 15 . Accordingly, treatment of 15 with allyltrimethylsilane in the presence of BF 3 · OEt 2 (1.2 equiv., CH 2 Cl 2 , –20 °C, 1 h) followed by decobaltation by treatment with tetra‐ n ‐butylammonium fluoride (TBAF) in THF, resulted in the exclusive isolation of α‐ C ‐glycoside 22b in 70 % yield (Scheme ). A polar intermediate was observed (TLC) during the course of the reaction.…”

Section: Resultsmentioning

confidence: 99%

Ferrier–Nicholas Cations from C‐3‐Alkynylglycals: Access to C‐3‐Branched Allylic Glycosides and Ring‐Opening Derivatives

et al. 2017

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Hexacarbonyldicobalt–C‐3‐alkynyl‐substituted glycal derivatives, when treated with BF3·OEt2 give rise to Nicholas‐stabilized Ferrier cation intermediates (Ferrier–Nicholas cations) that react with alcohols or C‐nucleophiles to give C‐3‐branched 2,3‐unsaturated glycosides or C‐glycosides, respectively. α‐C‐Glycosides were the sole compounds obtained when allyltrimethylsilane was used as the nucleophile. On the contrary, the reaction of C‐3‐alkynylglycals with heteroaryl or alcohol nucleophiles led to anomeric mixtures in which the β‐anomers prevailed. The presence of the hexacarbonyldicobalt–C‐3‐alkynyl substituent seems to be of key importance in the stereoselectivity of these transformations, since the reaction of C‐3‐alkynylglycals – devoid of the hexacarbonyldicobalt moiety – showed a preferred α‐stereoselectivity. Furthermore, a bis(indolyl) linear compound was obtained from the reaction of a hexacarbonyldicobalt–C‐3‐alkynylglycal with 2 equiv. of indole.

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Section: Resultsmentioning

confidence: 99%

Ferrier–Nicholas Cations from C‐3‐Alkynylglycals: Access to C‐3‐Branched Allylic Glycosides and Ring‐Opening Derivatives

et al. 2017

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“…Treatment of 27 with cerium ammonium nitrate (CAN) or TBAF resulted in simultaneous decomplexation and desilylation to give a stereoisomeric mixture of the free tetraphenylhexaoxy [6]pericyclynetetrol 3 d in 27 and 33 % yields, respectively. [22] The presence of two adjacent secondary carbinol vertices does not induce marked instabil- [8], and hydrogen bonds for 17 (see Figure 2 (10) hydrogen bonds (with H···A < r(A) + 2.000 and aDÀH···A > 1108)…”

Section: Wwwchemeurjorgmentioning

confidence: 97%

Functional [6]Pericyclynes: Synthesis through [14+4] and [8+10] Cyclization Strategies

Saccavini

Tedeschi

Maurette

et al. 2007

Chemistry A European J

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Critical analysis of possible strategies for the synthesis of novel carbo-benzene derivatives suggests several [(18-n)+n] routes for the preparation of hexaoxy[6]pericyclyne precursors. Beyond the previously attempted [9+9] symmetrical scheme (n=9), the a priori most selective strategies are those for which n=1, 4, 7, 10, 13, and 16. They involve a cyclizing double-propargylation of a C(18-n) omega-bis-terminal-skipped oligoyne containing (19-n)/3 triple bonds with a C(n) omega-dicarbonyl-skipped oligoyne containing (n-1)/3 triple bonds. To complement the previously used [11+7] strategy, the [14+4] and [8+10] strategies were thus explored. They proved to be efficient, affording seven novel hexaoxy[6]pericyclynes corresponding to six different substitution patterns. These compounds were obtained in 7-15 steps as mixtures of stereoisomers. Thus, by using dibenzoylacetylene as the C(4) electrophile, a [14+4] strategy allowed the synthesis of two hexaphenyl representatives with two or four free carbinol vertices. This approach also afforded tetraphenyl representatives in which the two remaining carbinoxy vertices were substituted with either two alkynyl or one 4-anisyl and one 4-pyridyl groups. By using the hexacarbonyldicobalt complex of butynedial as the C(4) electrophile, a [14+4] strategy also allowed the isolation of a tetraphenylhexaoxy[6]pericyclyne with two adjacent unsubstituted carbinol vertices. A regioisomer with two opposite unsubstituted carbinol vertices was obtained through an [8+10] strategy and its oxidation afforded the corresponding pericyclynedione. Several attempts at synthesizing diphenylhexaoxy[6]pericyclynes with four unsubstituted carbinoxy vertices are described. Only an [8+10] strategy allowed the generation of a fragile diphenylhexaoxy[6]pericyclyne with four adjacent unsubstituted carbinoxy vertices, which could be partly characterized. These results show that the synthesis of the nonsubstituted hexahydroxy[6]pericyclyne, the ring carbo-mer of [6]cyclitol, is a difficult challenge.

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“…While still capable of cleaving DNA like the natural products through cycloaromatization reactions and subsequent hydride abstraction by the diradical intermediate [2-4, 11, 12], these analogs offer potential advantages, such as more controlled activation of the compound in vivo [13][14][15][16][17][18][19][20][21][22][23] or increased selectivity for tumor cells [24 -30].…”

mentioning

confidence: 99%

Identification of the adduct between a 4-aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry

Sherman

Pierce

Brodbelt

et al. 2006

J. Am. Soc. Mass Spectrom.

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The interactions between a novel enediyne [1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium] (1) and various cytosine-containing oligonucleotides were studied using electrospray ionization mass spectrometry (ESI-MS) in a flow injection analysis mode useful for small volumes. This enediyne ligand, developed as a potential alternative to the highly cytotoxic natural enediynes, some of which have been successfully used as anti-tumor agents, has previously been shown to interact with DNA through frank strand scission as well as via the formation of adducts that lead to 2=-deoxycytidine-specific cleavage. Through ESI-MS, the structures of these adducts were examined and a sequence dependence of the 2=-deoxycytidine-specific cleavage was noted. Collisionally activated dissociation of the observed adducts confirmed the strength of the interactions between the enediyne and DNA and supports a direct linkage between the enediyne and the cytosine nucleobase, likely the result of a nucleophilic attack of the phenylethynyl group by the cytosine amine. , much effort has been directed towards identifying additional natural enediynes and evaluating their activities [2][3][4][5]. Currently, nearly twenty of these natural enediynes have been identified, including calichemicin ␥ 1 I [6,7], dynemicin [8], and the esperamicins [9,10]. While these enediynes offer extremely high cytotoxic activities, their clinical use as anti-tumor agents has been limited due to their delayed activities and general toxicity [2][3][4][5].To overcome the shortcomings of these natural enediynes, a range of synthetic analogs have been explored [3,11], each with the goal of improved properties for clinical use. While still capable of cleaving DNA like the natural products through cycloaromatization reactions and subsequent hydride abstraction by the diradical intermediate [2-4, 11, 12], these analogs offer potential advantages, such as more controlled activation of the compound in vivo [13][14][15][16][17][18][19][20][21][22][23] or increased selectivity for tumor cells [24 -30].To better evaluate the activities and properties of the many enediyne drug candidates as well as various other classes of drugs being developed, we present a technique for analyzing the interactions between these compounds and DNA using a flow injection analysis (FIA) mode coupled to an electrospray ionization mass spectrometer (ESI-MS). This analysis offers several key advantages over the traditional gel-based electrophoretic techniques. First, the dramatically better resolution of mass spectrometry versus polyacrylamide gel electrophoresis (PAGE) allows differentiation of similarly sized species, enabling the detection of very small molecules adducted to DNA. Second, while gel electrophoresis typically requires micrograms of sample, with our FIA method, a mass spectrum can easily be collected with nanograms, a sensitivity advantage of up to three orders of magnitude. Lastly, FIA-ESI-MS is easily adaptable to high-throughput analyses [31][32][33].In recent y...

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Facile Unmasking of Dicobalt Hexacarbonyl Complexes of 1-Cyclodecene-3,9-diynes (Enediynes)

Cited by 50 publications

References 12 publications

Ferrier–Nicholas Cations from C‐3‐Alkynylglycals: Access to C‐3‐Branched Allylic Glycosides and Ring‐Opening Derivatives

Ferrier–Nicholas Cations from C‐3‐Alkynylglycals: Access to C‐3‐Branched Allylic Glycosides and Ring‐Opening Derivatives

Functional [6]Pericyclynes: Synthesis through [14+4] and [8+10] Cyclization Strategies

Identification of the adduct between a 4-aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry

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