Investigation of a Convergent Route to Purpuromycin:  Benzofuran Formation vs Spiroketalization

Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.

doi:10.1021/ol061112j

Cited by 44 publications

(66 citation statements)

References 21 publications

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“…Further manipulations gave nitroalkyl-substituted pentamethoxynaphthalene derivative 65, prepared within 13 steps. [21] This group also prepared 6-vinylisocoumarin-3-carboxylate 70 (Scheme 15). Catechol (66) was converted into iodoarene 67 which was coupled with enol ether 68 in a Scheme 14.…”

Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

“…Acidic intramolecular condensation of the coupling product gave 6-hydroxymethylisocoumarin 69 and this compound was transformed into target compound 70, thus prepared within 16 linear steps. [21,22] Scheme 15. Synthesis of isocoumarin derivative 70 (Kozlowski and co-workers).…”

Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

“…The advanced spiroketalization precursor 72 was obtained in high overall yield via cycloadduct 71 (Scheme 16). [21] Unfortunately, this compound was not a suitable precursor for the rubromycins (see below, Scheme 20). which was converted into target aldehyde 77 by further transformations.…”

Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

“…Kozlowski and co-workers planned to carry out ketal formation on bis-phenolic ketone 72 as the key step in the synthesis of purpuromycin (6). [21] It turned out that 72 did not ketalize cleanly upon treatment with various Brønsted and Lewis acids; instead complex mixtures of products were produced (Scheme 20). One hypothesis for the reason of this failure was that the electron-rich naphthalene portion in 72 may undergo undesired oxidative side-reactions.…”

mentioning

confidence: 99%

“…[21] The authors attributed these findings to the markedly diminished nucleophilicity of the isocoumarin phenolic oxygen atom (Scheme 22 much faster than nucleophilic attack by the isocoumarin hydroxy function. Indeed, nucleophilic attack of this group may be strongly hampered by the extended conjugation present in this system (see sketch 94, Figure 3).…”

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confidence: 99%

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Rubromycins: Structurally Intriguing, Biologically Valuable, Synthetically Challenging Antitumour Antibiotics

et al. 2007

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Although known for more than 50 years the rubromycin family still constitutes a fascinating class of antitumour antibiotics. They are characterized by a challenging molecular architecture with the central spiroketal unit as the key feature and possess highly attractive biological properties. After a short treatment of the history of their isolation, structural elucidation and biosynthesis, their biological activities will briefly be summarized. This review strongly emphasizes the synthetic efforts aimed at these complex hexacyclic spiroketals. Reactions leading to simple spiroketal model compounds are described, followed by the synthetic approaches to the fully functionalized naphthalene and isocoumarin “wings”. The coupling of these units and their transformations into more advanced spiroketals demonstrate “the state of the art” in this research field. Only Danishefsky and co‐workers have so far completed the total synthesis of a fully functionalized rubromycin derivative; however, their product heliquinomycinone (103) is still only the aglycon of the natural product heliquinomycin (7), and it was prepared as the racemic compound. All these achievements and pitfalls reveal that increased engagement of synthetic organic chemists is required to develop new methods to make rubromycins and their analogues available by a modular approach and with reasonable efficacy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

Section: Syntheses Of Naphthalene and Isocoumarin Modules And Their Cmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Rubromycins: Structurally Intriguing, Biologically Valuable, Synthetically Challenging Antitumour Antibiotics

et al. 2007

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Organohalogenite‐Catalyzed Spiroketalization: Enantioselective Synthesis of Bisbenzannulated Spiroketal Cores

et al. 2016

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An ew core structure-motivated strategy for the intramolecular aromatic spiroketalization process wasf ound and used for the enantioselective synthesis of bisbenzannulated spiroketals,t he bioactive core of rubromycins,w ith high levels of enantioselectivity (up to 98% ee) via an organohalogenite-mediated asymmetric intramolecular aromatic spiroketalization. This is the first organocatalytic method for the construction of opticallyp ure bisbenzannulated spiroketals.Keywords: asymmetric synthesis; organocatalysis; organohalogen;spiroketalization Core-scaffold-lead synthesist hrough rapid construction of chiral molecular complexity around the biologically relevant framework using ah ighly efficient strategyisakey goal of organic andmedicinal synthesis.B enzannulated spiroketals,a saprivileged structural moietyf ound in al arge series of bioactive naturally occurring alkaloids andp harmaceutically relevant assays, such as Lysidicin [1] and rubromycins [2] ( Figure 1), exhibit ar ange of biological and pharmaceutical activities.[3] Although many strategies were designed to construct spiroketals [4] and related natural products, [5] the direct asymmetric catalytic approaches to access them are stillscarce.Recently,List [6] and Nagorny [7] developed the asymmetricc atalytic construction of aliphatic spiroketals by chiral phosphorica cid-catalyzed spiroketalizations (a,S cheme 1), respectively.H owever, comparedt o the asymmetric formation of aliphatic spiroketals,t he enantioselective construction of aromatic spiroketals represents ac onsiderable challenge because the aromatic hydroxy groups have less nucleophilicity.T herefore,itisnot surprising that the catalytic enantioselective synthesis of aromatics piroketals hasb een rarely

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Palladium‐Catalyzed Tandem Reaction of Alkyne‐Based Aryl Iodides and Salicyl N‐Tosylhydrazones to Construct the Spiro[benzofuran‐3,2′‐chromene] Skeleton

Shang

et al. 2016

Adv Synth Catal

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Ac onvenientp alladium-catalyzed tandem reactiono fa ryl iodides and salicyl N-tosylhydrazones has been achieved to afford as eries of compoundsc ontainingt he novels piro[benzofuran-3,2'-chromene] scaffold in moderate to good yields. This efficientc atalytic reaction, which tolerates various functional groups,c ombines alkyne-based 5exo-dig cyclization, palladium(II)c arbenem igratory insertion and intramolecular cyclization, generating three new bonds in one reaction.

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Investigation of a Convergent Route to Purpuromycin: Benzofuran Formation vs Spiroketalization

Cited by 44 publications

References 21 publications

Rubromycins: Structurally Intriguing, Biologically Valuable, Synthetically Challenging Antitumour Antibiotics

Rubromycins: Structurally Intriguing, Biologically Valuable, Synthetically Challenging Antitumour Antibiotics

Organohalogenite‐Catalyzed Spiroketalization: Enantioselective Synthesis of Bisbenzannulated Spiroketal Cores

Palladium‐Catalyzed Tandem Reaction of Alkyne‐Based Aryl Iodides and Salicyl N‐Tosylhydrazones to Construct the Spiro[benzofuran‐3,2′‐chromene] Skeleton

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