A Longitudinal Study of Alkaloid Synthesis Reveals Functional Group Interconversions as Bad Actors

Crossley, Steven W. M.; Shenvi, Ryan A.

doi:10.1021/acs.chemrev.5b00154

Cited by 64 publications

(41 citation statements)

References 296 publications

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“…The hapalindole family of marine natural products (e.g., 1 – 7 ) combines promising bioactivities with startling structural complexity ( Figure 2 A). 58 A retrosynthetic analysis 59 of these indole alkaloids, 60 aiming to divergently 61 access as many family members as possible, revealed 8 as a common precursor. 62 The union of indole and carvone ( 11 ) represented the most direct means to access 8 .…”

Section: A Radical Start: Oxidative Enolate Couplingmentioning

confidence: 99%

Radicals: Reactive Intermediates with Translational Potential

et al. 2016

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This Perspective illustrates the defining characteristics of free radical chemistry, beginning with its rich and storied history. Studies from our laboratory are discussed along with recent developments emanating from others in this burgeoning area. The practicality and chemoselectivity of radical reactions enable rapid access to molecules of relevance to drug discovery, agrochemistry, material science, and other disciplines. Thus, these reactive intermediates possess inherent translational potential, as they can be widely used to expedite scientific endeavors for the betterment of humankind.

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Section: A Radical Start: Oxidative Enolate Couplingmentioning

confidence: 99%

Radicals: Reactive Intermediates with Translational Potential

et al. 2016

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“…Finally, a natural product inspired scaffold 3 was generated . Numerous alkaloid syntheses have been reported and, on this basis, an efficient synthesis of the tetracyclic scaffold 3 was devised. Due to the complex ring structure and the natural‐product‐derived chemical features, this scaffold is particularly attractive for library synthesis.…”

Section: Methodsmentioning

confidence: 99%

Charting Biologically Relevant Spirocyclic Compound Space

Müller¹,

Berkenbosch²,

Benningshof³

et al. 2016

Chemistry A European J

118

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Spirocycles frequently occur in natural products and experience increasing interest in drug discovery, given their richness in sp centers and distinct three-dimensionality. We have systematically explored chemical space populated with currently available bioactive spirocycles. Compounds containing spiro systems were classified and their scaffolds and spirocyclic ring combinations analyzed. Nearly 47 000 compounds were identified that contained spirocycles in different structural contexts and were active against roughly 200 targets, among which several pharmaceutically relevant members of the G protein-coupled receptor (GPCR) family were identified. Spirocycles and corresponding compounds displayed notable scaffold diversity but contained only limited numbers of combinations of differently sized rings. These observations indicate that there should be significant potential to further expand spirocyclic chemical space for drug discovery, exploiting the privileged substructure concept. Inspired by those findings, we embarked on the design and chemical synthesis of three distinct novel spirocyclic scaffolds that qualify for downstream library synthesis, thus exploring principally new chemical space with high potential for pharmaceutical research.

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“…Thestructures for other products were assigned by analogy to 3m.T he trans stereochemistry of fused 5,6/6,6-bicyclic systems could be explained by the endo addition of azirine with the pendent diene,w hich is in line with the favorable endo cycloaddition for intermolecular aza-Diels-Alder reaction of azirines with dienes. [1a, 2c] At this stage,w eh ave established ar obust method to construct trans fused 5-6-3 and 6-6-3-tricyclic alkaloids.Given the fact that there are many N-heteropolycycles exhibiting excellent biological and pharmaceutical activities,a nd that there are numerous efforts toward the synthesis of these alkaloids, [5] we were encouraged to apply our method to access N-polycycles by using cyclic starting materials (Table 3). Theb enzofused tetracyclic aziridines 5a and 5b were accomplished smoothly from phenyl-conjugated dienyl vinyl azides 4a and 4b,r espectively (entries 1a nd 2).…”

Section: Angewandte Chemiementioning

confidence: 99%

Stereoselective Synthesis of Polycycles Containing an Aziridine Group: Intramolecular aza‐Diels–Alder Reactions of Unactivated 2H‐Azirines with Unactivated Dienes

Zhou

Pan

et al. 2016

Angew Chem Int Ed

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Vinyl azide with a pendent diene can undergo thermal decomposition to a related azirine intermediate, which was used immediately in an intramolecular aza-Diels-Alder reaction to furnish an aziridine-containing trans-fused tricyclic core structure with excellent stereoselectivity. The method provides a facile entry to complex polycyclic alkaliods which can be further elaborated by ring-opening reactions and ring expansion of the aziridine moiety, as well as by dihydroxylation of the alkene group.

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A Longitudinal Study of Alkaloid Synthesis Reveals Functional Group Interconversions as Bad Actors

Cited by 64 publications

References 296 publications

Radicals: Reactive Intermediates with Translational Potential

Radicals: Reactive Intermediates with Translational Potential

Charting Biologically Relevant Spirocyclic Compound Space

Stereoselective Synthesis of Polycycles Containing an Aziridine Group: Intramolecular aza‐Diels–Alder Reactions of Unactivated 2H‐Azirines with Unactivated Dienes

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