A Synthesis of the ABC Tricyclic Core of the Clionastatins Serves To Corroborate Their Proposed Structures

Tartakoff, Samuel S.; Vanderwal, Christopher D.

doi:10.1021/ol500265v

Cited by 16 publications

(18 citation statements)

References 16 publications

(29 reference statements)

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“…Our group has significant experience with alkene dichlorination and the remarkable difference that the substituents on proximal alcohols can have on diastereoselection. We have observed one particularly relevant case of selectivity reversal in a homoallylic alcohol superimposed on a cyclohexene ring, 45 and others wherein transient installation of electron-deficient acyl groups markedly improved reaction behavior. 46,47 In the case of 32 , the most interesting outcome came from a one-pot trifluoroacetylation/dichlorination sequence that provided a nearly equimolar mixture of expected diaxial and unexpected diequatorial dichlorides 33 (not separated at this stage).…”

Section: Resultsmentioning

confidence: 91%

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

et al. 2017

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The lissoclimides are unusual succinimide-containing labdane diterpenoids that were reported to be potent cytotoxins. Our short semi-synthesis and analogue-oriented synthesis approaches have provided a series of lissoclimide natural products and analogues that expanded the structure-activity relationships in this family. The semi-synthesis approach yielded significant quantities of chlorolissoclimide that permitted evaluation against the NCI’s 60 cell line panel and allowed us to obtain an X-ray co-crystal structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome. While it shares a binding site with other imide-based natural product translation inhibitors, chlorolissoclimide engages in a particularly interesting and novel face-on halogen-π interaction between the ligand’s alkyl chloride and a guanine residue. Our analogue-oriented synthesis provided many more lissoclimide compounds, which were tested against aggressive human cancer cell lines, and for protein synthesis inhibitory activity. Finally, computational modeling was used to explain the SAR of certain key compounds, setting the stage for structure-guided design of better translation inhibitors.

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Section: Resultsmentioning

confidence: 91%

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

et al. 2017

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“…[191] Similar to tribromides,t he use of trichlorides as an alternative to chlorine has been reported. [192] Chlorinations of several substrates,s uch as ketones, [193] alkenes, [194] and alkynes, [193] have used tetraethylammonium trichloride,asub- Table 13: Formulas of all experimentally known non-classical polyinterhalogen anions with more than three atoms. [a] Containing the atoms:…”

Section: Halogenation Reactionsmentioning

confidence: 99%

Polyhalogen and Polyinterhalogen Anions from Fluorine to Iodine

et al. 2020

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This Review deals with the evolving field of polyhalogen chemistry, specifically polyhalogen anions (polyhalides). In addition to a historical outline, current progress in synthetic approaches towards the formation of polyfluorides, polychlorides, polybromides, and polyinterhalides is also illustrated. The structural diversity of polyhalides has substantially increased in the past decade, especially for polychlorides and polybromides, which are commonly characterized by single‐crystal X‐ray diffraction, Raman spectroscopy, and quantum‐chemical calculations. Polyfluorides have been examined by sophisticated state‐of‐the‐art quantum‐chemical calculations and investigated spectroscopically in noble gas matrix‐isolation experiments under cryogenic conditions at 4 K. The bonding in such polyhalide systems is also discussed. The last Section deals with applications of polyhalides in halogenation reactions and electrochemistry as well as their use as reactive ionic liquids, emphasizing the promising future of polyhalogen chemistry.

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“…[49] Whereas the pseudodiaxial dichloride 117 (Scheme 22) was obtained as the major product from 116 via the expected diaxial addition pathway, dichlorination of the corresponding free alcohol 118 favored the desired pseudodiequatorial diastereomer 119 for the reasons that are currently unclear. Spectroscopic data were inconsistent with a change in ground state conformation between the protected and the unprotected substrates.…”

Section: Stereoselective Halogenation Methods and Applications In mentioning

confidence: 99%

“…Substrate (protecting group)-dependent diastereoselectivity reversal in alkene dichlorination was also observed by Va nderwal and co-workers in their synthetic studies toward the tricyclic core of the clionastatin B( 97,F igure 4). [49] Whereas the pseudodiaxial dichloride 117 (Scheme 22) was obtained as the major product from 116 via the expected diaxial addition pathway,dichlorination of the corresponding free alcohol 118 favored the desired pseudodiequatorial diastereomer 119 for reasons that are currently unclear. Spectroscopic data were inconsistent with achange in ground state conformation between the protected and the unprotected substrates.…”

Section: Diastereoselective Dichlorinationmentioning

confidence: 99%

Stereoselective Halogenation in Natural Product Synthesis

2016

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At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp3‐hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

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A Synthesis of the ABC Tricyclic Core of the Clionastatins Serves To Corroborate Their Proposed Structures

Cited by 16 publications

References 16 publications

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

Polyhalogen and Polyinterhalogen Anions from Fluorine to Iodine

Stereoselective Halogenation in Natural Product Synthesis

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