Mechanistic investigation and implications of a sacrificial aniline for the tandem cascade synthesis of 4-aza-podophyllotoxin analogues

Jeedimalla, Nagalakshmi; Johns, Jennifer; Roche, Stéphane

doi:10.1016/j.tetlet.2013.08.071

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…On the other hand, compound 1 also exhibited its interesting insecticidal and antifungal activities 3 4 5 . To find more potent podophyllotoxin derivatives, besides total synthesis of podophyllotoxin and its derivatives 6 7 8 9 10 11 , structural modifications of them have also attracted much attention in recent years 12 . To solve the instable trans-fused lactone of podophyllotoxin when exposed to mild base, a chlorine/bromine atom was introduced at its C-2α/β position to give 2α/β-halogenopodophyllotoxins ( 4 , Fig.…”

mentioning

confidence: 99%

Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins Reacting with Carboxylic Acids Mediated by BF3·Et2O

Fan

Zhi

Che

et al. 2015

Sci Rep

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Stereospecific nucleophilic substitution at the C-4α position of 2α-chloro-2′(2′,6′)-(di)halogenopicropodophyllotoxin derivatives with carboxylic acids mediated by BF3·Et2O was described. Interestingly, this stereoselective products were completely controlled by the reaction time. That is, if the reaction time was prolonged to 24.5–31 h, the resulting compounds were all transformed into the unusual C-ring aromatization products. Additionally, it demonstrated that BF3·Et2O and reaction temperature were the important factors for C-ring aromatization, and AlCl3 could be substituted for BF3·Et2O as a lewis acid for C-ring aromatization. Halogenation of E-ring of 2β-chloropodophyllotoxins with NCS or NBS also led to the same C-ring aromatization compounds. Especially compounds 5c, 6g and 7b exhibited insecticidal activity equal to that of toosendanin.

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confidence: 99%

Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins Reacting with Carboxylic Acids Mediated by BF3·Et2O

Fan

Zhi

Che

et al. 2015

Sci Rep

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“…As shown in Scheme , an efficient cascade synthesis of 4‐aza‐2,3‐didehydropodophyllotoxin analogues ( 173 a – f ) developed using a sacrificial electron deficient p ‐chloroaniline (method B). Compared with the results of method A (one‐pot three‐component condensation), method B exhibited higher yields and a wider scope for anilines …”

Section: Total Synthesis Of Podophyllotoxin and Its Analoguesmentioning

confidence: 78%

“… An efficient cascade synthesis of 4‐aza‐2,3‐didehydropodophyllotoxin analogues 173 a – f . (a) 2‐pentanol, 120 °C, 1 h; (b) 2‐pentanol, 120 °C, 2 h; (c) 2‐pentanol, 120 °C, 10 min; (d) 2‐pentanol, 120 °C, 30 min.…”

Section: Total Synthesis Of Podophyllotoxin and Its Analoguesmentioning

confidence: 99%

“…In general, 4β‐substituted analogues exhibited stronger cytotoxic activities than the corresponding 4α‐substituted ones . The carbon atom at the 4 position of the C‐ring substituted by nitrogen/oxygen atom could also yield potent 4‐aza/oxa‐podophyllotoxin analogues . The intact trans ‐fused lactone (D‐ring) is usually crucial for the cytotoxic activity .…”

Section: Future Prospectsmentioning

confidence: 99%

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Recent Advances in the Chemistry and Biology of Podophyllotoxins

Xiang

Che

2017

Chemistry A European J

175

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Podophyllotoxin and its related aryltetralin cyclolignans belong to a family of important products that exhibit various biological properties (e.g., cytotoxic, insecticidal, antifungal, antiviral, anti-inflammatory, neurotoxic, immunosuppressive, antirheumatic, antioxidative, antispasmogenic, and hypolipidemic activities). This Review provides a survey of podophyllotoxin and its analogues isolated from plants. In particular, recent developments in the elegant total chemical synthesis, structural modifications, biosynthesis, and biotransformation of podophyllotoxin and its analogues are summarized. Moreover, a deoxypodophyllotoxin-based chemosensor for selective detection of mercury ion is described. In addition to the most active podophyllotoxin derivatives in each series against human cancer cell lines and insect pests listed in the tables, the structure-activity relationships of podophyllotoxin derivatives as cytotoxic and insecticidal agents are also outlined. Future prospects and further developments in this area are covered at the end of the Review. We believe that this Review will provide necessary information for synthetic, medicinal, and pesticidal chemistry researchers who are interested in the chemistry and biology of podophyllotoxins.

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Reactions of Aldehydes and Ketones and Their Derivatives

Murray¹

2016

Organic Reaction Mechanisms · 2013

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Mechanistic investigation and implications of a sacrificial aniline for the tandem cascade synthesis of 4-aza-podophyllotoxin analogues

Cited by 8 publications

References 23 publications

Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins Reacting with Carboxylic Acids Mediated by BF3·Et2O

Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins Reacting with Carboxylic Acids Mediated by BF3·Et2O

Recent Advances in the Chemistry and Biology of Podophyllotoxins

Reactions of Aldehydes and Ketones and Their Derivatives

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