The enantiocontrolled total synthesis of natural (–)-goniomitine

Takano, Seiichi; Sato, Tsutomu; Inomata, Kohei; Ogasawara, Kunio

doi:10.1039/c39910000462

Cited by 69 publications

(43 citation statements)

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“…[24] The spectroscopic data of the synthetic goniomitine were identical to those reported in the literature. [2,[4][5][6][7][8] The remarkable synthetic efficiency and selectivity in the present one-pot multiple-bond-forming IORC process is worthy of additional comment. First, the use of NaHCO 3 as an additive for ozonolysis is of the utmost importance to get a high yield of 20.…”

Section: Methodsmentioning

confidence: 88%

“…The interesting molecular architecture and anti-proliferative activity of this natural product have made it a popular synthetic target. [3] To date, five total syntheses have been reported from the groups of Takano, [4] Pagenkopf, [5] Waser, [6] Mukai, [7] and Bach [8] Although building 2,3-difunctionalized indole followed by the stepwise formation of rings C and D is a common feature of these syntheses, the synthetic routes have been significantly shortened since the inaugural 28 step synthesis of Takano in 1991, thanks to the development of new reactions and strategies for the construction of the key 2,3-disubstituted indoles.…”

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confidence: 99%

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Palladium‐Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)‐Goniomitine

2013

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Section: Methodsmentioning

confidence: 88%

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confidence: 99%

Palladium‐Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)‐Goniomitine

2013

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“…Soon after the isolation 39 of (-)-goniomitine from Gonioma malagasy the total synthesis was reported by Takano and collaborators 40 , which also served to determine its absolute configuration as depicted in 1049, Scheme 17. Hájíček:…”

Section: First Total Synthesismentioning

confidence: 97%

Recent developments in syntheses of the post-secodine indole alkaloids. Part III: Rearranged alkaloid types

Hájíček¹

2011

Collect. Czech. Chem. Commun.

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The third part of a planned review on developments in the field of total and formal total synthesis of the post-secodine indole alkaloids focuses on types of rearranged alkaloids, i.e. on the skeletons with altered connectivities next to the indol(e)ine moiety, especially with a new bond to N-1. It reviews the synthesis of melodane, goniomitine, chippiine/dippinine, lirofoline and tronocarpine alkaloids, as well as alkaloids of secoschizozygane/vallesamidine, schizozygane and isoschizozygane type. It covers the literature from approximately 1991 up to May 2011. A review with 115 references.

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“…Owing to its antiproliferative activity and unusual structure, several groups have targeted goniomitine ( 1 ) for total synthesis . While modern approaches to this molecule have improved upon the seminal report by Takano and co‐workers, a synthesis of goniomitine ( 1 ) that employs asymmetric catalysis to achieve stereocontrol has not yet been demonstrated. To date, asymmetric syntheses of goniomitine ( 1 ) have relied on either enzymatic resolutions or chiral pool materials .…”

Section: Figurementioning

confidence: 99%

Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine, and (−)‐Quebrachamine

et al. 2016

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The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine are reported herein. Graphical Abstract Magnum (DH)PI:The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine are reported herein.Keywords total synthesis; allylic alkylation; asymmetric catalysis; Aspidosperma alkaloids; quaternary centers Monoterpene indole alkaloids have been extensively studied by chemists and biologists alike due to their vast structural diversity and broad biological activity. 1 (−)-Goniomitine (1), isolated from the bark of Gonioma malagasy, is an Aspidosperma alkaloid with a unique octahydroindolo[1,2-a][1,8]naphthyridine core (Figure 1). 2 The key structural differences Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript between goniomitine (1) and many Aspidosperma alkaloids (e.g., 2-4, Figure 1) 3 are the aminal functionality at C21 and the vestigial (2-hydroxy)ethyl moiety at C7. 4 Biosynthetically, these features are believed to arise from oxidative degradation of the tryptamine fragment in vincadifformine (4, Scheme 1A) followed by fragmentation and N1-C21 recombination. 5 Cyclizations between an indole and a C2-tethered iminium moiety (e.g., 5, Scheme 1B) are remarkably chemoselective. In the case of a C3-substituted indole fragment (e.g., 5, R 1 ≠ H), cyclization proceeds via C-N bond formation to furnish aminalcontaining tetracycle 6, as seen in previous syntheses of goniomitine (1). [5][6][7] Conversely, a C3-unsubstituted indole fragment (e.g., 5, R 1 = H) undergoes C-C bond formation followed by rearomatization to arrive at alternative tetracycle 7, a core that is present in numerous alkaloids (e.g., 2 & 4). 8 We anticipated that iminium intermediates such as 5 could be accessed in straightforward fashion from compounds containing a dihydropyrido[1,2-a]indolone (DHPI) core (Scheme 1C). Retrosynthetically, we envisioned that the propylamine fragment in 5 could arise from an anti-Markovnikov hydroamination of the allyl functionality in α-quaternary lactam 8. Given our lab's long-standing interest in the asymmetric synthesis of all-carbon quaternary centers, we believed that we could employ our Pd-catalyzed allylic alkylation chemistry to construct the quaternary stereocenter at C20 in an enantioselecti...

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The enantiocontrolled total synthesis of natural (–)-goniomitine

Cited by 69 publications

References 15 publications

Palladium‐Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)‐Goniomitine

Palladium‐Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)‐Goniomitine

Recent developments in syntheses of the post-secodine indole alkaloids. Part III: Rearranged alkaloid types

Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine, and (−)‐Quebrachamine

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