Synthesis of Natural Products Containing Medium‐Size Carbocycles by Ring‐Closing Alkene Metathesis

Blanchard, Nicolas; Eustache, Jacques

doi:10.1002/9783527629626.ch1

Cited by 28 publications

(20 citation statements)

References 128 publications

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“…4a). Notably, unique architectures of bioactive natural products such as medium-sized rings33 ( E , F , I and K ), bridge-head bicyclic structures34 ( J and P ) and β-lactam rings3536 ( G ) were successfully incorporated into the pyrimidine-containing core skeletons. When we overlaid the energy-minimized conformers of each scaffold in 3D space by aligning the pyrimidine substructure, we clearly demonstrated the skeletal diversity and structural complexity of the resulting polyheterocycles (Fig.…”

Section: Resultsmentioning

confidence: 99%

Diversity-oriented synthetic strategy for developing a chemical modulator of protein–protein interaction

et al. 2016

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Diversity-oriented synthesis (DOS) can provide a collection of diverse and complex drug-like small molecules, which is critical in the development of new chemical probes for biological research of undruggable targets. However, the design and synthesis of small-molecule libraries with improved biological relevance as well as maximized molecular diversity represent a key challenge. Herein, we employ functional group-pairing strategy for the DOS of a chemical library containing privileged substructures, pyrimidodiazepine or pyrimidine moieties, as chemical navigators towards unexplored bioactive chemical space. To validate the utility of this DOS library, we identify a new small-molecule inhibitor of leucyl-tRNA synthetase–RagD protein–protein interaction, which regulates the amino acid-dependent activation of mechanistic target of rapamycin complex 1 signalling pathway. This work highlights that privileged substructure-based DOS strategy can be a powerful research tool for the construction of drug-like compounds to address challenging biological targets.

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Section: Resultsmentioning

confidence: 99%

Diversity-oriented synthetic strategy for developing a chemical modulator of protein–protein interaction

et al. 2016

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“…[12] Lebreton et al employed metathesis to synthesize the alkaloids anatabine and anabasine (Scheme 3). [16] When the diene 11 was treated with the catalyst G1, no reaction occurred.…”

Section: Anabasinementioning

confidence: 99%

“…[12] In the course of our approach to FR182877 (Figure 2), we employed a metathesis reaction to synthesize the A ring.…”

Section: Fr182877 and Hexacyclinic Acidmentioning

confidence: 99%

Progress in Metathesis Through Natural Product Synthesis

Prunet

2011

Eur J Org Chem

105

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This article covers case studies in natural product syntheses with comments on various aspects of metathesis reactions and on how the difficulties encountered in these syntheses have led to better understanding of these reactions or to more effective reaction conditions and catalysts. Ring‐closingmetathesis leading to small and medium‐sized rings is discussed, followed by macrocycle formation, asymmetric ring‐closing metathesis, and cross metathesis.

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“…These side reactions are particularly problematic in the synthesis of 7and 8-membered ring compounds. Over the past years, several methods to form 8-membered rings have been developed, including ring-closing metathesis, [6] alkynyl/dienyl metal complex assisted cyclizations, [7] metal-catalyzed [4+4], [8] [4+2+2], [9] and [6+2] [10] cyclo-additions, as well as oxabicyclic metal-promoted ring-opening reactions. [11] However, the harsh reaction conditions, poor functional group tolerance, inevitable by-product formation or the necessity of noble metal catalysts can put limitations on the general applicability of the existing methods in both academic and industrial settings.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals

Zhou¹,

Vlugt²,

Bruin

2020

Preprint

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The metalloradical activation of o-aryl aldehydes with cobalt(II) porphyrin complexes as catalysts produces cobalt(III)-carbene radical intermediates, providing a novel and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [Co<sup>II</sup>(TPP)]-catalyzed (TPP = tetraphenylporphyrin) synthesis of two types of 8 membered ring compounds; novel dibenzocyclooctenes and unique monobenzo-cyclooctadienes. The method was successfully applied to a variety of substrates, producing several 8-membered ring compounds in good yields and with excellent substituent tolerance. DFT calculations and experimental results suggest that the reactions proceed via initial hydrogen atom transfer from the bis-allylic/benzallylic C-H bond to the carbene radical moiety, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are formed by dissociation of o quinodimethanes (o-QDMs) from the catalyst that undergo an uncatalyzed ring-closure reaction involving 8-pi-cyclisation, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral benzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.

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Synthesis of Natural Products Containing Medium‐Size Carbocycles by Ring‐Closing Alkene Metathesis

Cited by 28 publications

References 128 publications

Diversity-oriented synthetic strategy for developing a chemical modulator of protein–protein interaction

Diversity-oriented synthetic strategy for developing a chemical modulator of protein–protein interaction

Progress in Metathesis Through Natural Product Synthesis

Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals

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