Isolation, Total Synthesis and Biological Activity of Phenanthroindolizidine and Phenanthroquinolizidine Alkaloids

Li, Zaiguo; Jin, Zhong; Huang, Runqiu

doi:10.1055/s-2001-18703

Cited by 82 publications

(7 citation statements)

References 63 publications

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“…Angewandte Chemie tectures, phenanthroindolizidine alkaloids, such as antofine (2) and tylophorine (3), are attractive targets for total synthesis. [2,17] Alkaloids 1, 2, and 3 could be readily prepared from amides 9 y and 9 z (Scheme 2).…”

Section: Scheme 1 Proposed Mechanismmentioning

confidence: 99%

“…[2,17] Alkaloids 1, 2, and 3 could be readily prepared from amides 9 y and 9 z (Scheme 2). In the presence of [(Cp*RhCl 2 ) 2 ] (2.5 mol %), the reaction of 9 y and 9 z produced 2-pyridones 10 y and 10 z in excellent yields.…”

Section: Scheme 1 Proposed Mechanismmentioning

confidence: 99%

“…

The rhodium(III)-catalyzed oxidative CÀH activation has received significant interest in recent years because of its high efficiency, selectivity, and functional-group tolerance.

…”

mentioning

confidence: 99%

“…While a number of synthetic methods for the construction of these scaffolds have been reported, [1][2][3][4] the development of conceptually different synthetic approaches is still of great interest.The rhodium(III)-catalyzed oxidative CÀH activation has received significant interest in recent years because of its high efficiency, selectivity, and functional-group tolerance. [5] Generally, these reactions require stoichiometric amounts of external oxidants [Eq.…”

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confidence: 99%

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confidence: 99%

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Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Liu

Park

2012

Angewandte Chemie

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The indolizidine structural motif forms the core of many natural products with pharmacological relevance, such as indolizidine [1] and phenanthroindolizidine [2] alkaloids (septicine (1), antofine (2), and tylophorine (3)), camptothecin (4, CPT), [3] and aromathecin alkaloids [4] (rosettacin (5) and 22hydroxyacuminatine (6)). While a number of synthetic methods for the construction of these scaffolds have been reported, [1][2][3][4] the development of conceptually different synthetic approaches is still of great interest.The rhodium(III)-catalyzed oxidative CÀH activation has received significant interest in recent years because of its high efficiency, selectivity, and functional-group tolerance. [5] Generally, these reactions require stoichiometric amounts of external oxidants [Eq. (1)], [6] thus resulting in the generation of undesired waste. Recently, Fagnou et al. reported an oxidizing-directing-group strategy [7] for the rhodium-catalyzed synthesis of isoquinolones by intermolecular CÀH activation of N-methoxy/pivaloyloxy benzamides and alkynes [Eq.(2); Piv = pivaloyl], [8] which not only obviates the need for an external oxidant, but also increases the reactivity and selectivity under mild conditions. During our investigation of the reactivity of a-oximino carbenoids, [9] we observed facile intramolecular N À O insertion of oxime ether moieties, which results in the formation of 2-alkoxy/aryloxy-2H-azirines. [10] The cleavage of the N À O bond plays an important role in Fagnous rhodium-catalyzed intermolecular CÀH activation of N-methoxy/pivaloyloxy benzamides and in our NÀO insertion of a-oximino carbenes. Based on this observation, we became interested in the intramolecular reaction of alkyne-tethered hydroxamic esters [Eq. (3)]. The successful development of this reaction would lead to a general and facile synthesis of hydroxyalkyl-substituted isoquinolone/2pyridone derivatives, which could be readily transformed into indolizidine scaffolds. Herein, we wish to report these results, and the total synthesis of (AE)-antofine, (AE)-septicine, (AE)tylophorine, and rosettacin based on rhodium(III)-catalyzed C À H bond functionalization as the key step.Our synthetic attempts began with the reaction of 7 a by employing Fagnous intermolecular reaction conditions [7] ( Table 1, entries 1 and 2). We found that treatment of 7 a with [(Cp*RhCl 2 ) 2 ] (2.5 mol %) and CsOAc (30 mol %) in MeOH at 60 8C gave isoquinolones 8 a and 8 a' (29:1) in 98 % yield in 0.2 hours (Table 1, entry 1). Similar results were obtained with a reduced catalyst loading (0.5 mol %) and reaction temperature, however, a longer reaction time was required in this case (12 h; Table 1, entry 2). Improved

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Section: Scheme 1 Proposed Mechanismmentioning

confidence: 99%

Section: Scheme 1 Proposed Mechanismmentioning

confidence: 99%

“…

The rhodium(III)-catalyzed oxidative CÀH activation has received significant interest in recent years because of its high efficiency, selectivity, and functional-group tolerance.

…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Liu

Park

2012

Angewandte Chemie

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Intramolecular Palladium‐Catalyzed Direct Arylation vs. Heck Reactions: Synthesis of Pyrroloisoquinolines and Isoindoles

et al. 2009

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Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives^[1]

Hsu

2011

Adv Synth Catal

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In the presence of cobalt catalysts and tetramethylethylenediamine (TMEDA), the iodine atom in (S)-2-(iodomethyl)pyrrolidines was replaced by an aryl or an alkynyl group from the corresponding Grignard reagent, and the coupling products were obtained in good to excellent yields (16 examples; 75-94% yields). The scope and limitations of this protocol were examined. The stereochemistry of the pyrrolidines was unaffected by the reaction conditions. The coupling products are important building blocks of phenanthroindolizidine alkaloids. Palladium-catalyzed formal [4 + 2] cycloaddition of 2,2'-diiodobiphenyl with the thus-generated (S)-2-(3-trimethylsilyl-2-propynyl)pyrrolidine gave a good yield of the desilylated phenanthrene, which was then converted into unnatural (+)-(S)-tylophorine by the Pictet-Spengler cyclization.

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Isolation, Total Synthesis and Biological Activity of Phenanthroindolizidine and Phenanthroquinolizidine Alkaloids

Abstract: A review showing the efforts toward the isolation, total synthesis and biological activity of phenanthroindolizidine and phenanthroquinolizidine alkaloids from 1981 to 2000 is presented. 4 Biological Activity 5 Conclusions

Cited by 82 publications

References 63 publications

Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Intramolecular Palladium‐Catalyzed Direct Arylation vs. Heck Reactions: Synthesis of Pyrroloisoquinolines and Isoindoles

Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives^[1]

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Isolation, Total Synthesis and Biological Activity of Phenanthroindolizidine and Phenanthroquinolizidine Alkaloids

Abstract: A review showing the efforts toward the isolation, total synthesis and biological activity of phenanthroindolizidine and phenanthroquinolizidine alkaloids from 1981 to 2000 is presented. 4 Biological Activity 5 Conclusions

Cited by 82 publications

References 63 publications

Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Rhodium(III)‐Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)‐Antofine, (±)‐Septicine, (±)‐Tylophorine, and Rosettacin

Intramolecular Palladium‐Catalyzed Direct Arylation vs. Heck Reactions: Synthesis of Pyrroloisoquinolines and Isoindoles

Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives[1]

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Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives^[1]