Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

Park, Sangbin; Kang, Gyumin; Kim, Chansu; Kim, Dongwook; Han, Sunkyu

doi:10.1038/s41467-022-32902-z

Cited by 14 publications

(22 citation statements)

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“…Collective Total Synthesis of C4-Oxygenated Securinine-Type Alkaloids via Stereocontrolled Diversifications on the Piperidine CoreParkS.KangG.KimC.KimD.HanS. Park, S. Kang, G. Kim, C. Kim, D. Han, S. Nat. Commun.2022135149 …”

Section: Key Referencesmentioning

confidence: 99%

“…We next aimed for a unified synthesis of C4-oxidized securinine-type alkaloids. 4 developed (Scheme 8A, Challenge 2). Finally, an effective method to control the C2 configuration should be identified (Scheme 8A, Challenge 3).…”

Section: Total Synthesis Of C4-oxygenated Securinine-type Alkaloids V...mentioning

confidence: 99%

“…Soc.202214489328937 Cross-dehydrogenative coupling (CDC) reaction between an aldehyde and an electron-deficient olefin was developed to interconnect two monomeric units comprising flueggeacosine B . Collective Total Synthesis of C4-Oxygenated Securinine-Type Alkaloids via Stereocontrolled Diversifications on the Piperidine CoreParkS.KangG.KimC.KimD.HanS. Park, S. Kang, G. Kim, C. Kim, D. Han, S. Nat. Commun.2022135149 …”

Section: Key Referencesmentioning

confidence: 99%

“…We next aimed for a unified synthesis of C4-oxidized securinine-type alkaloids . Even though groups I and II (C4-oxygenated members) constitute 44% of all known high-oxidation-state Securinega alkaloids, phyllanthine ( 42 ) had remained the only member to succumb to synthesis among the C4-oxidized Securinega alkaloids. , We identified three key challenges en route to a unified synthetic solution to these type of natural products.…”

Section: Synthesis Of High-oxidation State Securinega Alkaloidsmentioning

confidence: 99%

“…It is our sincere hope that lessons we have learned during our synthetic journey would benefit other chemists working on organic synthesis. 4 Various regio-and stereoselective oxidations and rearrangements tactics were applied to the synthesis of seven C4-oxygenated securinine-type alkaloids.…”

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Synthesis of High-Order and High-Oxidation State Securinega Alkaloids

2023

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Conspectus Securinega alkaloids, composed of more than 100 members characterized by the compact tetracyclic scaffold, have fascinated the synthetic community with their structural diversity and notable bioactivities. On the basis of the structural phenotype, oligomerizations and oxidations are major biosynthetic diversification modes of the basic Securinega framework. Despite the rich history of synthesis of basic monomeric Securinega alkaloids, the synthesis of oligomeric Securinega alkaloids, as well as oxidized derivatives, has remained relatively unexplored because of their extra structural complexity. In the first half of this Account, our synthetic studies toward high-order Securinega alkaloids are described. We aimed to establish a reliable synthetic method to form C14–C15′ and C12–C15′ bonds, which are prevalent connection modes between monomers. During our total synthesis of flueggenine C (9), we have invented an accelerated Rauhut–Currier reaction capable of forming the C14–C15′ bond stereoselectively. Installation of the nucleophilic functionality to the Michael acceptor, which ushers the C–C bond forming conjugate addition to follow the intramolecular pathway, was the key to success. The C12–C15′ linkage, which was inaccessible via an accelerated Rauhut–Currier reaction, was established by devising a complementary cross-coupling/conjugate reduction-based dimerization strategy that enabled the total synthesis of flueggenines D (11) and I (14). In this approach, the C12–C15′ linkage was established via a Stille cross-coupling, and the stereochemistry of the C15′ position was controlled during the following conjugate reduction step. In the later half of this Account, our achievements in the field of high-oxidation state Securinega alkaloids synthesis are depicted. We have developed oxidative transformations at the N1 and C2–C4 positions, where the biosynthetic oxidation event occurs most frequently. The discovery of a VO(acac)2-mediated regioselective Polonovski reaction allowed us to access the key 2,3-dehydroallosecurinine (112). Divergent synthesis of secu′amamine A (62) and fluvirosaones A (60) and B (61) was accomplished by exploiting the versatile reactivities of the C2/C3 enamine moiety in 112. We have also employed a fragment-coupling strategy between menisdaurilide and piperidine units, which allowed the installation of various oxygen-containing functionality on the piperidine ring. Combined with the late-stage, light-mediated epimerization and well-orchestrated oxidative modifications, collective total synthesis of seven C4-oxygenated securinine-type natural products was achieved. Lastly, the synthesis of flueggeacosine B (70) via two synthetic routes from allosecurinine (103) was illustrated. The first-generation synthesis (seven overall steps) employing Pd-catalyzed cross-coupling between stannane and thioester to form the key C3–C15′ bond enabled the structural revision of the natural product. In the second-generation synthesis, we have invented visible-light-mediated, Cu-catalyzed cross-d...

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Section: Key Referencesmentioning

confidence: 99%

Section: Total Synthesis Of C4-oxygenated Securinine-type Alkaloids V...mentioning

confidence: 99%

Section: Key Referencesmentioning

confidence: 99%

Section: Synthesis Of High-oxidation State Securinega Alkaloidsmentioning

confidence: 99%

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Synthesis of High-Order and High-Oxidation State Securinega Alkaloids

2023

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“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea

Han

2022

Bulletin Korean Chem Soc

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Natural product synthesis has lain at the heart of organic chemistry. Complex structures of natural products have inspired chemists to develop new methods and strategies. The utility and robustness of newly developed methodologies have been tested by their application into total synthesis. With the necessity to establish a solid health-related and biomedical Korean industrial ecosystem, a historically belittled sector when compared to well-invested manufacturing and electronics industries in Korea, there has been enormous recent progress in the Korean organic chemical research. Accordingly, impressive syntheses of complex secondary metabolites that feature unique tactics and ingenious strategies have been reported by synthetic organic chemists in Korea. Herein, recent advancements (mostly after 2010) in natural product synthesis from Korea are depicted. Representative accomplishments from researchers in Korea are presented with an emphasis on unique methods and strategies that are utilized into their synthetic approaches.

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Diastereoselectivity Switch During Alkene Reductions: Diastereodivergent Syntheses of Molecular Fossils via MHAT or Homogeneous Catalytic Hydrogenation Reactions

Maior

Costa

Ligiéro

et al. 2023

Chemistry A European J

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Sixteen geosterane derivatives were synthesized in up to 57 % overall yields in four steps harnessing the olefin cross‐metathesis (OCM) and Metal hydride H atom transfer (MHAT) or homogeneous hydrogenation reactions as key steps. Drawing on this strategy, the diastereomeric ratio (d. r.) reached up to 24 : 1 for the thermodynamic isomer and 7 : 1 for the other isomer in the hydrogenation step. In a geological sample from northeast Brazil, we confirmed the putative structures previously assumed as methyl 2‐(3α‐5αH‐cholestan) acetate, methyl 2‐(3β‐5αH‐cholestan)acetate, and methyl 6‐(3β‐5αH‐cholestan)hexanoate, as well three new molecular fossils of approximately 120 million years old. We also proved the migration marking ability of those carboxylic acids derived from forerunner geosteranes during an oil migration event, which suggests their aptitudes as molecular odometers. Our approach demonstrated swiftness and effectiveness in preparing a molecular library of geological biomarkers would also be appropriate to generate stereochemical diversity in molecular libraries for medicinal chemistry and natural product anticipation.

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Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

Cited by 14 publications

References 44 publications

Synthesis of High-Order and High-Oxidation State Securinega Alkaloids

Synthesis of High-Order and High-Oxidation State Securinega Alkaloids

“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea

Diastereoselectivity Switch During Alkene Reductions: Diastereodivergent Syntheses of Molecular Fossils via MHAT or Homogeneous Catalytic Hydrogenation Reactions

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