Synthesis of a Benzolactone Collection using Click Chemistry

Ritschel, Jan; Sasse, Florenz; Maier, Martin E.

doi:10.1002/ejoc.200600681

Cited by 22 publications

(10 citation statements)

References 49 publications

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“…Based on the suspicion that the dienone moiety may be responsible for loss of in vivo activity (it has been shown that DTT rapidly inactivates radicicol by conjugate addition to the dienone) [59] a new analog was designed [64], which capitalizes on an extremely efficient copper catalyzed cycloaddition of an azide with an alkyne (Scheme 3) [65]. The efficiency and permissibility of this latter reaction had already inspired Maier and coworkers to use it for the generation of simpler resorcylide analogs [66]. Attesting to the efficiency of the click reaction and the synthetic design, the triazole-cycloproparadicicol could be obtained in only 11 steps (longest linear sequence) with 20% overall yield!…”

Section: Diverted Synthesis and Diversity-orien-ted Synthesis Of Natumentioning

confidence: 98%

Hsp90 Inhibition with Resorcylic Acid Lactones (RALs)

Winssinger¹,

Fontaine²,

Barluenga

2009

CTMC

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Heat shock protein 90 (Hsp90) is an ATP-dependent chaperone which is involved in the post-translational maturation and stabilization of over one hundred proteins ("its clients"). In the absence of Hsp90's chaperoning, its clients are misfolded and degraded via ubiquitin-proteasome pathway. It has become the focus of intense drug discovery efforts as its activity has been implicated in diverse pathologies ranging from oncology to neurodegenerative and infectious diseases. The most promising inhibitors reported to date inhibit the ATPase activity by binding to the N-terminal ATP pocket. Radicicol, a member of the resorcylic acid lactones (RALs), represents an important pharmacophore to this end. Efforts towards the development of this pharmacophore and its SAR are reviewed herein.

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Section: Diverted Synthesis and Diversity-orien-ted Synthesis Of Natumentioning

confidence: 98%

Hsp90 Inhibition with Resorcylic Acid Lactones (RALs)

Winssinger¹,

Fontaine²,

Barluenga

2009

CTMC

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“…This way the triazoles 56 and 57 were obtained (Scheme 6). 40 These analogues showed cytotoxicity in the micromolar range, pointing to the crucial role of the enamide side chain in 31E.…”

Section: Organic and Biomolecular Chemistry Reviewmentioning

confidence: 99%

Design and synthesis of analogues of natural products

Maier

2015

Org. Biomol. Chem.

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142

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In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error.

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“…With the goal of developing an efficient DTS strategy toward salicylihalamide analogs, the Maier group has reported several routes to the macrocycle. Further, they produced a simplified macrocycle bearing an alkynyl side chain ( 83 ), leading to the production of several triazole analogs of type 84 using click chemistry (Scheme A) . In this example, the generation of the simplified macrocycle bearing a terminal alkyne ( 83 ) allowed for the coupling of a multitude of different azides.…”

Section: The Role Of Diverted Total Synthesis In Drug Discoverymentioning

confidence: 99%

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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Synthesis of a Benzolactone Collection using Click Chemistry

Cited by 22 publications

References 49 publications

Hsp90 Inhibition with Resorcylic Acid Lactones (RALs)

Hsp90 Inhibition with Resorcylic Acid Lactones (RALs)

Design and synthesis of analogues of natural products

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

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