An Unusual Ring‐Contraction/Rearrangement Sequence for Making Functionalized Di‐ and Triquinanes

Nagaraju, Chinta; Prasad, Kavirayani R.

doi:10.1002/ange.201407680

Cited by 7 publications

(2 citation statements)

References 18 publications

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“…14 Its unique architectural features include: the presence of eight stereogenic centers, three all-carbon quaternary stereocenters, high oxygen atom content, as well as congested tetracyclic ring system (Figure 2). 15 There are a handful of reports available for the construction of polyquinane frameworks, and the selected reports include cycloaddition reaction, 16 photochemical reactions, 17 tandem oxy-cope reactions, 18 radical cyclization, 19 the Weiss−Cook condensation, 20 annulation, 21 the Diels−Alder (DA) reaction, 22 rearrangement, 23 enoneolefin cyclization, 24 etc. However, to the best of our knowledge, a pentaquinane framework with more than four 5-membered rings fused in both a linear and an angular fashion has not been reported to date, and its synthesis is indeed a challenging task for organic chemists due to the presence of quaternary carbon atom(s), and no general approach was found to deal with the construction of tri-, tetra-, and pentaquinanes.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthetic Strategies to Diverse Polyquinanes via Olefin Metathesis: Access to the Basic Core of Crinipellin, Presilphiperfolanol, and Cucumin

et al. 2019

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A rapid and useful synthetic approach to various polyquinane-based natural products was accomplished efficiently by employing ring-rearrangement metathesis and ring-closing metathesis as key steps. Here, we report the synthesis of stereochemically well-defined cis-anti-cis triquinanes (1, 2), tetraquinanes (3, 4), a novel pentaquinane 5, and fused [5-5-5-6] tetracyclic systems (6, 7) that are present in crinipellin, presilphiperfolanol, cucumin, etc. Hence, the current strategy may be suitable for the synthesis of various complex natural and unnatural cyclopentanoid targets. Moreover, our approach to the newly synthesized pentaquinane 5 has paved the way for various complex polyquinanes/molecules having significant applications in theoretical and medicinal chemistry.

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Section: ■ Introductionmentioning

confidence: 99%

Synthetic Strategies to Diverse Polyquinanes via Olefin Metathesis: Access to the Basic Core of Crinipellin, Presilphiperfolanol, and Cucumin

et al. 2019

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“…The synthesis of sesquiterpenes containing multiple fused 5-membered rings through multi-step reactions has required the development of new synthetic methodology. 20–27 Interest in this family of natural products has also been inspired by the biological activity of certain linear triquinanes. For example, capnellane triquinanes exhibit sub-micromolar toxicity against leukemia and renal cancer cell lines, 28 and capnellene itself exhibits potent anti-neuroinflammatory and analgesic effects.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of Cucumene Synthase, a Terpenoid Cyclase That Generates a Linear Triquinane Sesquiterpene

et al. 2018

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Linear triquinanes are sesquiterpene natural products with hydrocarbon skeletons consisting of three fused 5-membered rings. Importantly, several of these compounds exhibit useful anti-cancer, anti-inflammatory, and antibiotic properties. However, linear triquinanes pose significant challenges to organic synthesis due to the structural and stereochemical complexity of their hydrocarbon skeletons. To illuminate nature’s solution to the generation of linear triquinanes, we now describe the crystal structure of Streptomyces clavuligerus cucumene synthase. This sesquiterpene cyclase catalyzes the stereospecific cyclization of farnesyl diphosphate to form a linear triquinane product, (5S,7S,10R,11S)-cucumene. Specifically, we report the structure of the wild-type enzyme at 3.05 Å resolution and the structure of the T181N variant at 1.96 Å resolution, both in the open active site conformations without any bound ligands. The high-resolution structure of T181N cucumene synthase enables inspection of the active site contour, which adopts a three-dimensional shape complementary to a linear triquinane. Several aromatic residues outline the active site contour and are believed to facilitate cation-π interactions that would stabilize carbocation intermediates in catalysis. Thus, aromatic residues in the active site not only define the template for catalysis, but these residues also play a role in reducing activation barriers in the multi-step cyclization cascade.

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Synthetic Approaches to Crinipellin Based Tetraquinanes via Ring‐Rearrangement Metathesis and Ring‐Closing Metathesis

Kotha

Keesari

2021

Asian J Org Chem

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Herein, we have studied the synthetic approaches to tetraquinanes that are present in crinipellin type natural products by employing ring-rearrangement metathesis (RRM) and ring-closing metathesis (RCM) as key steps. These studies involve finding the suitable alkylation sequence to prepare desired RRM/RCM precursors. Methyl-tetraquinane has been assembled by employing a regio-, and stereoselective methylation followed by allylation sequence. Whereas, allyltetraquinane was constructed by following the allylation-RRM sequence. Interestingly, spiro-quinanes rearranges to fusedquinanes when olefinic moiety is present adjacent to the spiro-ring under RRM conditions. Additionally, several di-, and triquinane derivatives reported during this study were also found in diverse polyquinane natural products. The present strategy utilizes the vinyl derivative of exo-dicyclopentadiene-1-one, and produce several intricate polycyclic systems. Our strategy may be useful to design various medicinally important "drug-like" molecules.

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An Unusual Ring‐Contraction/Rearrangement Sequence for Making Functionalized Di‐ and Triquinanes

Cited by 7 publications

References 18 publications

Synthetic Strategies to Diverse Polyquinanes via Olefin Metathesis: Access to the Basic Core of Crinipellin, Presilphiperfolanol, and Cucumin

Synthetic Strategies to Diverse Polyquinanes via Olefin Metathesis: Access to the Basic Core of Crinipellin, Presilphiperfolanol, and Cucumin

Crystal Structure of Cucumene Synthase, a Terpenoid Cyclase That Generates a Linear Triquinane Sesquiterpene

Synthetic Approaches to Crinipellin Based Tetraquinanes via Ring‐Rearrangement Metathesis and Ring‐Closing Metathesis

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