Synthesis of an Advanced Intermediate of the Macrotricyclic Core of Roseophilin

Hong, Meiling; Liu, Hui; Sun, Lixin; Jia, Feifei; Liu, Yuanyuan; Jiang, Qingwei; Song, Chuanjun; Chang, Junbiao

doi:10.1055/s-0031-1289882

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…In the same year, Frontier and co-workers reported examples of both α-(propenoyl)pyrroles and β-(propenoyl)pyrroles without any N -protection (eq ). While >50 examples of Nazarov cyclization have since been reported with α-(propenoyl)pyrroles, − to our knowledge there are only three prior examples of analogous β-substituted pyrroles. − Moreover, regardless of pyrrole substitution position, most such examples stem from model studies rather than as integral to total syntheses. Examples of the latter include synthesis of (±)-roseophilin. ,,,, …”

Section: Discussionmentioning

confidence: 99%

“…Examples of the latter include synthesis of (±)-roseophilin. 49,50,52,54,56 The Nazarov reaction process also can be regarded as an intramolecular Michael addition (5-endo-trig) 58 of the pyrrole with the appended propenoyl substituent. Intermolecular examples of such pyrrole C-alkylations date to as early as 1951 and were typically carried out with either activated reactants or somewhat forcing conditions.…”

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

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Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a

Zhang

Lindsey

2017

J. Org. Chem.

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Bacteriochlorophylls contain a bacteriochlorin macrocycle bearing an annulated fifth ring. The fifth ring, termed the isocyclic ring or ring E, is equipped with 13-oxo and 13-carbomethoxy substituents. Herein, a general route to stable, synthetic bacteriochlorophyll analogues is described. Knoevenagel condensation (∼40 mM, rt, CHCl, piperidine/AcOH/molecular sieves) of a dihydrodipyrrin-carboxaldehyde (AD half) and a dihydrodipyrrin substituted with a β-ketoester (BC half) forms a propenone bearing the two halves (a hydrobilin analogue). Subsequent treatment (0.2 mM) with acid (Yb(OTf), CHCN, 80 °C) promotes a double ring-closure process: (i) condensation between the α-position of pyrrole ring A and the α-acetal unit attached to pyrroline ring B forms the bacteriochlorin macrocycle, and (ii) Nazarov cyclization of the β-(propenoyl)-substituted ring C forms the isocyclic ring (E). Five new bacteriochlorins bearing various substituents (alkyl/alkyl, aryl, and alkyl/ester) at positions 2 and 3 (β-pyrrole sites, ring A) and 13 carboalkoxy groups (R = Me or Et) were constructed in 37-61% yield from the hydrobilin analogues. The BC half and AD half are available in five and eight steps, respectively, from the corresponding pyrrole-2-carboxaldehyde and unsaturated ketone. The bacteriochlorins exhibit absorption spectra typical of bacteriopheophytins (free base bacteriochlorophylls), with a strong near-infrared absorption band (707-751 nm).

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Section: Discussionmentioning

confidence: 99%

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a

Zhang

Lindsey

2017

J. Org. Chem.

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“…Since indole and pyrrole rings fused with cyclopentane are present in natural products such as bruceolline, paspaline, yuehchukene, and roseophilin and in pharmaceutical drugs such as laropiprant (MK-0524), we tried to apply the cascade reaction to the construction of these frameworks (Scheme ). , The trial began with the cascade reaction of pyrrole-2-carboxaldehyde 1H and indole-2-carboxaldehyde 1I , of which nitrogen was not protected. However, treatment of 1H by method A resulted in gradual decomposition and recovery of phenyl homoallylic alcohol.…”

Section: Resultsmentioning

confidence: 99%

Syntheses of Polycyclic Tetrahydrofurans by Cascade Reactions Consisting of Five-Membered Ring Selective Prins Cyclization and Friedel–Crafts Cyclization

et al. 2018

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A novel cascade reaction consisting of a five-membered ring selective Prins cyclization and a subsequent Friedel-Crafts cyclization is reported. Treatment of homocinnamyl alcohols and aromatic aldehydes with BF·OEt in CHCl afforded hydrocyclopentafurans. Also hydrocyclopentafurans underwent the same cascade reaction after its furan ring cleavage upon treatment with BF·OEt at room temperature. Various combinations of hydropentafurans and aromatic aldehydes or indole aldehydes permitted divergent synthesis of diquinane-furans stuck in aromatic rings.

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Flow Photo-Nazarov Reactions of 2-Furyl Vinyl Ketones: Cyclizing a Class of Traditionally Unreactive Heteroaromatic Enones

2018

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Nazarov reactions of 2-furyl vinyl ketones and related heteroaromatic enones, to produce furan-fused cyclopentanones using a flow photochemical approach, are described. Compounds possessing this connectivity between heterocycle and ketone (2-furyl, 2-benzofuryl, 2-thiophene-yl, and 2-benzothiophene-yl) have traditionally proven difficult or impossible to cyclize with typical Brønsted and Lewis acid mediated methods. Using mild flow photochemistry conditions and acetic acid (AcOH) or hexafluoroisopropanol (HFIP) as solvent, these compounds were found to cyclize in 45-97% yields, with typical UV exposure times of 3.4-6.8 min. In all cases, 2-furyl and 2-thiophene-yl enones cyclized, whereas 2-benzofuryl and 2-benzothiophene-yl enones exhibited divergent properties with reactivity patterns tied to the identity of the vinyl group. This report discloses the first photo-Nazarov reactions of tetrahydropyridine-substituted 2-furyl ketones, providing a direct approach to the corresponding fused heterocyclic motifs built around a central cyclopentanone. These motifs constitute the core structures of biologically active natural products, including the marine alkaloid nakadomarin A.

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Synthesis of an Advanced Intermediate of the Macrotricyclic Core of Roseophilin

Abstract: A facile approach for the preparation of a cyclopenta[b]pyrrole derivative, the key precursor in Frontier's synthesis of the macrotricyclic core of roseophilin, was developed. The key steps involved two successive pyrrole acylations and a Sc(OTf) 3catalyzed Nazarov cyclization reaction.

Cited by 3 publications

References 5 publications

Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a

Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a

Syntheses of Polycyclic Tetrahydrofurans by Cascade Reactions Consisting of Five-Membered Ring Selective Prins Cyclization and Friedel–Crafts Cyclization

Flow Photo-Nazarov Reactions of 2-Furyl Vinyl Ketones: Cyclizing a Class of Traditionally Unreactive Heteroaromatic Enones

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