Rapid Synthesis of the N‐Methylwelwitindolinone Skeleton.

Mackay, James; Bishop, R.; Rawal, Viresh H.

doi:10.1002/chin.200549179

Cited by 3 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These were then advanced to vicdifluoro derivatives 34 and 35 using deoxofluorination conditions described by Yin et al 29 Removal of the N-tosyl groups finally afforded model compounds 10 and 14. 30 The synthesis of gem-difluoro derivatives 11−13 started with Weinreb amides 36 and 37, which were obtained from the corresponding carboxylic acids 38 and 39 (Scheme 3). 24,31 N-Tosyl-protected amides 36 and 37 were then converted to ketones 40−42, respectively, upon treatement with MeMgBr or EtMgBr.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…32 Finally, the targeted model compounds 11−13 were isolated after deprotection upon exposure to potassium hydroxide in boiling ethanol. 30 The threo and erythro vicinal difluoro-and bis-vicinal trifluorobutyl derivatives (15−18) were derived from a single common precursor, alkyne 49 (Scheme 4). An optimized multigram-scale three-step synthesis of 49 started from 3methylindole 67, N-tosylation to 68, 33 and subsequent Wohl− Ziegler bromination to intermediate 48, 34 which was subjected to Cu(I)-promoted coupling with methyl propiolate 35 to afford alkyne 49 in 47% yield over three steps after crystallization.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

et al. 2015

View full text Add to dashboard Cite

The synthesis of a collection of 3-substituted indole derivatives incorporating partially fluorinated n-propyl and n-butyl groups is described along with an in-depth study of the effects of various fluorination patterns on their properties, such as lipophilicity, aqueous solubility, and metabolic stability. The experimental observations confirm predictions of a marked lipophilicity decrease imparted by a vic-difluoro unit when compared to the gem-difluoro counterparts. The data involving the comparison of the two substitution patterns is expected to benefit molecular design in medicinal chemistry and, more broadly, in life as well as materials sciences.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Welwitindolinones are alkaloids found in the cyanobacteria Hapalosiphon weltischii, Westiella intracta, Fischerella muscicola, and F. major [123,124]. The extracts which significantly contain N-methylwelwitindolinone (56) were found to have potent biological activities including antifungal, larvicidal, and insecticidal properties [124].…”

Section: Welwitindolinones and Derivativesmentioning

confidence: 99%

“…The extracts which significantly contain N-methylwelwitindolinone (56) were found to have potent biological activities including antifungal, larvicidal, and insecticidal properties [124]. Most welwitindolinones possess a densely functionalized oxindole-fused bicyclo[4,3,1]decane ring system (Figure 10).…”

Section: Welwitindolinones and Derivativesmentioning

confidence: 99%

“…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]. The key intermediate compound V was subjected to aldehyde reduction via a hydrazine (oxidation to the oxindole), alcohol oxidation and oxime formation, and Curtius rearrangement of oxime to isothiocynate to furnish 57.…”

Section: Welwitindolinones and Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Synthesis, Protein Kinase Inhibitory Potencies, and in Vitro Antiproliferative Activities of Meridianin Derivatives

et al. 2011

View full text Add to dashboard Cite

The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents.

show abstract

Rapid Synthesis of the N‐Methylwelwitindolinone Skeleton.

Cited by 3 publications

References 4 publications

Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

Marine Natural Products as Models to Circumvent Multidrug Resistance

Synthesis, Protein Kinase Inhibitory Potencies, and in Vitro Antiproliferative Activities of Meridianin Derivatives

Contact Info

Product

Resources

About