Acutumine and acutumidine, chlorine containing alkaloids with a novel skeleton (2): Chemical proof

Tomita, Masaru; Okamoto, Yasuko; Kikuchi, Takeo; Osaki, Kunihiro; Nishikawa, Masao; Kamiya, Kanichi; Sasaki, Yoshio; Matoba, Katsuhide; Goto, Kakuji

doi:10.1016/s0040-4039(00)71621-2

Cited by 32 publications

(11 citation statements)

References 2 publications

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“…The mixture was concentrated in vacuo, and the residue was purified by flash chromatography (SiO 2 , 1.5 × 6 cm, 1% Et 3 N in 5–15% MeOH–CH 2 Cl 2 gradient elution), affording 1 (1.1 mg, 0.0027 mmol, 52%) and enol ether regioisomer 49 (0.3 mg, 0.00075 mmol, 14%). For 1 : white film, [α] 25 D −171 ( c 0.81, pyridine), lit2b [α] 25 D −206 ( c 0.69, pyridine); 1 H NMR (pyridine- d 5 , 500 MHz) δ 8.47 (br, s, 1H), 5.61 (s, 1H), 5.20 (dd, J = 11.8, 6.8 Hz, 1H), 5.03 (s, 1H), 4.04 (s, 3H), 3.80 (s, 3H), 3.73 (s, 3H), 3.16 (t, J = 12.0 Hz, 1H), 3.07 (d, J = 15.5 Hz, 1H), 2.69-2.63 (m, 3H), 2.54 (d, J = 15.5 Hz, 1H), 2.45-2.42 (m, 1H), 2.39 (s, 3H), 1.65-1.62 (m, 1H); 13 C NMR (pyridine- d 5 , 125 MHz) δ 201.3, 192.8, 188.9, 159.7, 138.9, 105.5, 72.9, 70.7, 68.3, 60.4, 60.1, 58.8, 57.8, 53.2, 51.6, 47.2, 41.4, 38.5, 36.3; IR (film) ν max 3410, 2899, 2817, 1655, 1641, 1364, 1205, 1079, 935 cm −1 ; HRMS (ESI) m/z 398.13655 (MH + , C 19 H 24 ClNO 6 H + requires 398.13649).…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Total Synthesis of (−)-Acutumine

Tartakoff

Castle

2009

J. Org. Chem.

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An account of the total synthesis of the tetracyclic alkaloid (−)-acutumine is presented. A firstgeneration approach to the spirocyclic subunit was unsuccessful due to incorrect regioselectivity in a radical cyclization. However, this work spawned a second-generation strategy in which the spirocycle was fashioned via a radical-polar crossover reaction. This process merged an intramolecular radical conjugate addition with an enolate hydroxylation, and created two stereocenters with excellent diastereoselectivity. The reaction was promoted by irradiation with a sunlamp, and a ditin reagent was required for aryl radical formation. These facts suggest that the substrate may function as a sensitizer, thereby facilitating homolytic cleavage of the ditin reagent. The propellane motif of the target was then installed via annulation of a pyrrolidine ring onto the spirocycle. The sequence of reactions used included a phenolic oxidation, an asymmetric ketone allylation mediated by Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, a one-pot ozonolysis-reductive amination, and a Lewis acid promoted cyclization of an amine onto an α,β-unsaturated dimethyl ketal. Further studies of the asymmetric ketone allylation demonstrated the ability of the Nakamura reagent to function well in a mismatched situation. A TiCl 4 -catalyzed regioselective methyl enol etherification of a 1,3-diketone completed the synthesis.

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Section: Methodsmentioning

confidence: 99%

Enantioselective Total Synthesis of (−)-Acutumine

Tartakoff

Castle

2009

J. Org. Chem.

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“…Its structure, determined nearly fifty years later by Tomita and co-workers [37] using X-ray crystallography, revealed a highly oxygenated tetracyclic skeleton containing four contiguous stereogenic carbon atoms of which two are quaternary. Other structurally intriguing features are the presence of a spiroannulated cyclopentenone-chlorocyclopentane subunit as part of an oxidized hexahydroindole ring and an azapropellane core.…”

Section: Acutuminementioning

confidence: 99%

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

et al. 2016

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Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quarternary carbon atoms in their intricate structures are reviewed with twelve representative examples. Emphasis has been put on the methods to create quarternary carbon stereocenters, including syntheses of the same natural product from different groups, thereby showcasing diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quarternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information section.

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“…The first such examples appear to be acutumine and acutumidine [71], isolated from the plant Smomentum acutum in 1967 (185). Very recently, two chlorinated bis-indole alkaloids were isolated from Melodinus celastroides (e.g., 72) (186).…”

Section: Ohmentioning

confidence: 99%

Naturally Occurring Organohalogen Compounds--A Survey

Gribble¹

1992

J. Nat. Prod.

356

199

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More than 1 5 0 0 different halogenated chemicals are produced and discharged into our biosphere by plants, marine organisms, insects, bacteria, fungi, and other natural processes. In a few cases, the quantities of these naturally occurring halogenated compounds far exceed the amounts of the same chemicals from anthropogenic sources. Furthermore, the evidence is overwhelming that natural enzymatic, thermal, and other processes are constantly occurring in the oceans, in the atmosphere, and in the soil that lead to the formation of chlorinated and brominated phenols and many other halogenated chemicals, including dioxins, that previously were thought only to result from the actions of man. Moreover, it is clear that these natural processes have been producing halogenated compounds and have been an important component of our ecosystem for eons.

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Acutumine and acutumidine, chlorine containing alkaloids with a novel skeleton (2): Chemical proof

Cited by 32 publications

References 2 publications

Enantioselective Total Synthesis of (−)-Acutumine

Enantioselective Total Synthesis of (−)-Acutumine

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

Naturally Occurring Organohalogen Compounds--A Survey

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