Synthesis of spiroacetal-triazoles as privileged natural product-like scaffolds using “click chemistry”

Choi, Ka Wai; Brimble, Margaret A.

doi:10.1039/b808454h

Cited by 13 publications

(13 citation statements)

References 55 publications

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“…All 1D ( 1 H, 13 C, and selective NOESY experiments) and 2D NMR ( 1 H-1 H COSY, HSQC, NOESY, HMBC) have been recorded in deuterated solvents (euriso-top) on a Bruker AVANCE 250, 300 or 400 MHz instrument. The chemical shifts are reported in ppm relative to the solvent residual peak (d (CHCl 3 ) = 7.26 ppm, d (CHDCl 2 /CH 2 Cl 2 ) = 5.32 ppm).…”

Section: Instrumentationmentioning

confidence: 99%

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Metal‐Free 1,5‐Regioselective Azide–Alkyne [3+2]‐Cycloaddition

Kloß

Köhn

Jahn

et al. 2011

Chemistry An Asian Journal

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[3+2]‐cycloaddition reactions of aromatic azides and silylated alkynes in aqueous media yield 1,5‐disubstituted‐4‐(trimethyl‐silyl)‐1H‐1,2,3‐triazoles. The formation of the 1,5‐isomer is highly favored in this metal‐free cycloaddition, which could be proven by 1D selective NOESY and X‐ray investigations. Additionally, DFT calculations corroborate the outstanding favoritism regarding the 1,5‐isomer. The described method provides a simple alternative protocol to metal‐catalyzed “click chemistry” procedures, widening the scope for regioselective heavy‐metal‐free synthetic applications.

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Section: Instrumentationmentioning

confidence: 99%

“…alkyne cycloadditions have been applied. [13] Notably, the TMS-group can lead to a high selectivity considering 4-TMS-triazoles. Initially, a combination of steric interactions and electronic effects, which lead to an increase of the electrophilicity of the b-carbon of alkynes, was assumed.…”

Section: Introductionmentioning

confidence: 99%

Metal‐Free 1,5‐Regioselective Azide–Alkyne [3+2]‐Cycloaddition

Kloß

Köhn

Jahn

et al. 2011

Chemistry An Asian Journal

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“…The retrosynthesis adopted for the desired spiroacetal-nucleosides 11 hinged on disconnection of the anomeric C-N bond linking the spiroacetal to the nucleobase. With this idea in mind, it was proposed that previously prepared ethoxy-spiroacetal 12 22 can be converted to acetoxy-spiroacetal 10 which is then elaborated to nucleosides 11. Ethoxy-spiroacetal 12 is synthesised from ketone Scheme 1 Synthesis of spiroacetal-nucleosides 11 generated by the nucleosidation of acetoxy-spiroacetal 10 with a range of persilylated bases under Vorbr üggen conditions.…”

Section: Resultsmentioning

confidence: 99%

“…21 We recently reported the synthesis of a series of spiroacetal hybrids containing a triazole unit at the anomeric position that provided an isostere to mimic the biological relevant peptide bond. 22 Using a similar rationale, we herein report the synthesis of a series of spiroacetal-nucleosides 11 generated by the nucleosidation of acetoxy-spiroacetal 10 with several persilylated bases under Vorbr üggen conditions (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of spiroacetal-nucleosides as privileged natural product-like scaffolds

Choi

Brimble

2009

Org. Biomol. Chem.

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“…11 We have also synthesized several indole analogues of the CJ antibiotics (1-4) 12 that subsequently displayed inhibitory activity against H. pylori. Prompted by our recent observation that indole analogues of 1-4 exhibit activity against H. pylori, 13 combined with our ongoing interest in the synthesis of triazole analogues of biologically active natural products 14 and natural product-like scaffolds, 15 we decided to undertake the synthesis of benzotriazole analogues of the aforementioned CJ antibiotics 1-4 with the idea of improving their bioactivity. We herein describe the convergent synthesis of several benzotriazole analogues of the CJ antibiotics 1-4 using a highly regioselective 1,3-dipolar cycloaddition of a dioxygenated benzyne and a range of alkyl azides.…”

mentioning

confidence: 99%

Synthesis of Benzotriazole Analogues of the Helicobactericidal Agents CJ-13,015, CJ-13,102, CJ-13,108, and CJ-13,104 Using a Regioselective 1,3-Dipolar Cycloaddition

Atkinson¹,

Sperry²,

Brimble³

2010

Synlett

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A regioselective 1,3-dipolar cycloaddition of a disubstituted aryne and various alkyl azides facilitates access to benzotriazole analogues of several anti-Helicobacter pylori antibiotics.Helicobacter pylori has been shown by epidemiological studies to have an etiological role in several diseases, including gastric and duodenal ulcers, distal gastric cancer, mucosal-associated lymphoid tissue (MALT) lymphoma (cancer of the B cell lymphocytes), and was implicated in the cause of 5.6% of all cancers worldwide in 2002. 1 This microaerophilic, Gram-negative bacterium 2 has been estimated to infect the stomach of over half of the world's population making it the planet's most widespread infection. 3 In the majority of cases, infection will persist for the lifetime of an individual in the absence of medical intervention. 4Current treatments for H. pyroli infections are complex and rely on broad range antibiotics in combination with proton-pump inhibitors and bismuth salts. 5 The first line of treatment cures less than 20% of patients due to unpleasant side effects which often leads to noncompliance. 5 H. pyroli also quickly develops resistance to the currently used antibiotics clarithromycin and metronidazole. 5 The complex nature of current treatments combined with their often poor success rates and side effects dictates an obvious need for new helicobactericidal treatments. 5,6 In a screening program to isolate such compounds, Dekker and co-workers isolated several new phthalide antibiotics 1-6 ( Figure 1) with specific anti-H. pylori activity from the basidiomycete Phanerochaete velutina CL6387. 7 Two structurally related compounds, spirolaxine 7 8a and its methyl ether 8 8b have been isolated from the cultures of Phanerochaete chrysosporium and they have also been shown to be good inhibitors of the H. pylori bacterium. 7,12 The ongoing studies in our laboratory regarding the synthesis of potential anti-H. pylori compounds has witnessed the racemic syntheses of CJ-13,015, CJ-13,102, CJ-13,108, CJ-13,104 (1-4) 9 together with the total synthesis and stereochemical assignment of the complex spiroacetal-containing phthalides CJ-12,954 (5), CJ-13,014 (6) 10 and spirolaxine methyl ether (8). 11 We have also synthesized several indole analogues of the CJ antibiotics (1-4) 12 that subsequently displayed inhibitory activity against H. pylori. 13 Figure 1 Phthalide containing antibiotics with anti-H. pylori activity O M e M e O O O O 7 O M e M e O O O R 7 O M e M e O O O H 7 O O O C J -1 3 , 0 1 5 ( 1 ) R = O A c ; C J -1 3 , 1 0 2 ( 2 ) R = H ; C J -1 3 , 1 0 8 ( 3 ) O M e R O O O O 3 O C J -1 3 , 0 1 4 ( 6 ) C J -1 2 , 9 5 4 ( 5 ) R R R R C J -1 3 , 1 0 4 ( 4 ) R = H ; s p i r o l a x i n e ( 7 ) R = M e ; s p i r o l a x i n e m e t h y l e t h e r ( 8 ) O M e M e O O O O O R R R 4 R S 4 O M e M e O O O O O R R R

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Synthesis of spiroacetal-triazoles as privileged natural product-like scaffolds using “click chemistry”

Cited by 13 publications

References 55 publications

Metal‐Free 1,5‐Regioselective Azide–Alkyne [3+2]‐Cycloaddition

Metal‐Free 1,5‐Regioselective Azide–Alkyne [3+2]‐Cycloaddition

Synthesis of spiroacetal-nucleosides as privileged natural product-like scaffolds

Synthesis of Benzotriazole Analogues of the Helicobactericidal Agents CJ-13,015, CJ-13,102, CJ-13,108, and CJ-13,104 Using a Regioselective 1,3-Dipolar Cycloaddition

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