Stereoselective synthesis of the macrocyclic core (C7–C19) of carolacton

Sharma, G. V. M.; Reddy, Sheri Venkata

doi:10.1039/c3ra44227f

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…9 Kirschning in particular has been quite prolific as they have disclosed both the first total synthesis 10 and uncovered useful information regarding the structure—activity relationship (SAR) by analog synthesis (Figure 1). 11 These studies elucidated that both drastic (increased ring size) and even small conformational changes to the 12-membered macrocycle, for example, introduction of an α,β -unsaturated ketone or an epimeric allylic alcohol, abolish activity.…”

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confidence: 99%

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms

et al. 2017

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The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S. mutans, causing acid-mediated cell death during biofilm formation; however, its complex structure limits its utility. Herein, we report the diverted total synthesis and biological evaluation of a rationally designed library of simplified analogs that unveiled three unique biofilm phenotypes further validating the role of natural product synthesis in the discovery of new biological phenomena.

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confidence: 99%

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms

et al. 2017

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“…12,13 There have also been a handful of publications toward the synthesis of carolacton that fit outside the scope of this account. [14][15][16][17] To complete our route toward the natural product, we proposed precursor acid 2 and side-chain 3 (Scheme 1). 11 Starting from gulonolactone-derived diol 4, oxidation and subsequent Wittig olefination allows for synthesis of alkene 5 (Scheme 2).…”

Section: Back To the Beginning: The Initial Synthetic Highlightsmentioning

confidence: 99%

Collaboration in Natural Product Total Synthesis: Carolacton – A Decade of Discovery

Solinski

Wuest

2020

Synlett

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Carolacton, a macrocyclic natural product with impressive anti-biofilm biological activity, has been a focus in multiple research groups for the past decade. Chemists and biologists, alike, have been interested in uncovering the mechanism of action and have made great strides towards this goal. Carolacton causes cellular defects in Streptococcus mutans biofilm, which leads to decreases in cellular viability. As biological targets have been uncovered, synthetic chemists have devised synthetic routes that have helped uncover the important chemical functionalities that lead to biological activity. Herein, we discuss our synthetic collaboration that galvanized an entire research program around the natural product carolacton.

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“…In addition to the total syntheses discussed above, carolacton has been the subject of significant synthetic effort, resulting in a number of partial syntheses and one formal synthesis (Scheme ). In 2013, Ghosh reported routes to the alcohol ( 131 ) and alkyne ( 133 ) .…”

Section: Other Examples Of 12‐membered Macrolactonesmentioning

confidence: 99%

“…During the course of their endeavor, Kirshning's total synthesis was reported, intersecting both of these intermediates in their key NHK coupling, thus resulting in a formal synthesis by Ghosh (Scheme A). In 2013, Reddy published a route to the carolacton macrocycle 142 via an esterification/deprotection/RCM sequence (Scheme C). In the same year, Sabitha reported the successful synthesis of the full carolacton carbon skeleton 145 , also utilizing an NHK coupling of 143 and 144 in a manner similar to Kirschning (Scheme D).…”

Section: Other Examples Of 12‐membered Macrolactonesmentioning

confidence: 99%

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Twelve‐membered macrolactones: privileged scaffolds for the development of new therapeutics

Brzozowski

Wuest

2017

Chem Biol Drug Des

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Natural products commonly produced as secondary metabolites of various plants and micro-organisms represent a diverse chemical space of compounds. The diversity of natural products makes them an attractive target for interrogation by both chemists and biologists alike. Indeed, the study of 12-membered macrolactones has already led to the discovery of lead drug compounds and new biological targets, which has motivated the development of diverted total synthetic routes to libraries of analogs. This review explores the discovery, biological characterization, and synthesis of several 12-membered macrolactones, exploiting examples that underscore their importance in the drug discovery field. It is our hope that this review will motivate further interest in this class of natural products, a group of molecules that we think merit the classification of 'privileged scaffolds' within the medicinal chemistry community, to further investigate and develop novel compounds with promising bioactivity. K E Y W O R D Santibiotic, biosynthesis, diverted total synthesis, macrolactone, natural product

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Stereoselective synthesis of the macrocyclic core (C7–C19) of carolacton

Cited by 10 publications

References 19 publications

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms

Collaboration in Natural Product Total Synthesis: Carolacton – A Decade of Discovery

Twelve‐membered macrolactones: privileged scaffolds for the development of new therapeutics

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