Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products

Fu, Tsung Hao; McElroy, William T.; Shamszad, Mariam; Heidebrecht, Richard W.; Gulledge, Brian M.; Martin, Stephen F.

doi:10.1016/j.tet.2013.03.010

Cited by 31 publications

(23 citation statements)

References 100 publications

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“…In Gang's method, the synthetic pathway begins with coupling of a functional cyclohexanone using iodine promoted bromoindole addition, followed by ring closure to form the key intermediate compound I. Thereafter, 57 was formed by chlorination through vinyltrimethylstannane oxidation to oxindole, isotopically enhanced tethered nitrene insertion, and isothiocyanate introduction (Scheme 11a) [126][127][128]. In Rawal's approach (Scheme 11b), the coupling of silylenolether II with nucleophile bromoindole III was achieved by Lewis acid to form the corresponding cyclohexanone IV which then produces the key intermediate V by palladium-catalyzed enolate arylation [124,129].…”

Section: Harmine and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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Section: Harmine and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…[55] Porco's rapid synthesis of polyprenylated acylphloroglucinol (PPAP) analogues is another impressive example of using annulative allylic alkylation with a1,3-dual electrophile to synthesize bicyclic ketones (Scheme 35). Although [3.3.2] bicycle 150 was isolated in 59 %y ield, none of the desired [4.3.1] product 149 was detected and the authors chose to pursue alternative routes.…”

Section: Scheme29 Othersyntheses Of Bicyclo[331] Systemsmentioning

confidence: 99%

Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

Trost

Kalnmals

2019

Chemistry A European J

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Metal-catalyzed allylic alkylation reactions between dual nucleophiles and dual electrophiles represent ap owerful set of methodsf or the synthesis of small-, medium-, and even large-sized rings. Using this strategy,ahandful of simple allylic diol derivatives can be transformed into a broad array of complexc arbo-and heterocycles of varying ring sizes in just as ingle step. Because of their ability to rapidly generate complexity, annulative allylic alkylationr eactions between dual nucleophiles and dual electrophiles have been extensively employed in the total synthesis of both naturalp roducts and pharmaceuticalcompounds.Scheme1.GeneralScheme for metal-catalyzed allylic alkylation.Scheme2.GeneralScheme for annulative allylic alkylation reactionsu sing a dual electrophile.Scheme3.Differenttypesofa nnulativeallylic alkylation reactions.Scheme4.GeneralScheme for allylic alkylation reactionsi nvolving 1,1-substitutions.

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“…Although these structural subunits are not present in N -methylwelwitindolinone C isothiocyanate 125,126 and actinophyllic acid, 127 related transformations can also be readily applied to the syntheses of these complex alkaloids.…”

Section: Applications Of Vinylogous Mannich and Related Reactionsmentioning

confidence: 99%

“…141 Our synthetic approach to this intriguing alkaloid featured the reaction of the electron rich diene 272 with the stabilized cation generated upon ionization of 273 , which may be viewed as a vinylogous iminium ion, to provide 274 (Scheme 52). 126 Cyclization of 274 via a Pd(0)-catalyzed intramolecular enolate arylation provided 275 . Oxidative processing of the furan ring in 275 then led to the γ-acyloxy enone 276 that underwent a novel π-allylation reaction to deliver 277 , which possesses the bridged tetracyclic framework of the welwitindolinone alkaloids.…”

Section: Applications Of Vinylogous Mannich and Related Reactionsmentioning

confidence: 99%

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Martin

2017

J. Org. Chem.

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Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding.

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Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products

Cited by 31 publications

References 100 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

Natural Products and Their Mimics as Targets of Opportunity for Discovery

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