Total synthesis of (±)-lycoposerramine-R, a novel skeletal type of  Lycopodium alkaloid

Ishida, Hiroaki; Kimura, Shinya; Kogure, Noriyuki; Kitajima, Mariko; Takayama, Hiromitsu

doi:10.1016/j.tet.2014.11.038

Cited by 29 publications

(10 citation statements)

References 41 publications

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“…Due to its rather unusual structure, which also features an α‐pyridone, it has attracted significant synthetic interest . This has so far resulted in racemic syntheses by the Sarpong and Takayama groups as well as an enantioselective synthesis by the latter . The key quaternary stereocenter was set by Eschenmoser–Claisen, Diels–Alder, and alkylation reactions, respectively, in these studies.…”

Section: Methodsmentioning

confidence: 99%

A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

2016

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An enantioselective total synthesis of the Lycopodium alkaloid lycoposerramine R is presented. It relies on a base-mediated cyclization that resembles the Conia-ene reaction of ynones and gold-catalyzed variants thereof. Thus, hydrindanones and other functionalized ring systems bearing an exocyclic alkene can be rapidly accessed at room temperature without noble metal catalysis or substrate preactivation.

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Section: Methodsmentioning

confidence: 99%

A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

2016

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“…A similar strategy was used with other inexpensive and commercially available keto-esters 23 and leading to bicyclic scaffolds 25, which is the core-structure of the lycoposerramine natural product ( Scheme 3 ) [ 50 , 51 , 52 , 53 , 54 ]. With this synthesis design and following standard diversification reactions as depicted in Scheme 2 , the final small molecules ( 25 – 30 ) were obtained with high stereoselectivity ( 25a :(6:1); 25b :(10:1) Scheme 3 ).…”

Section: Resultsmentioning

confidence: 99%

Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products

Murali

Hristeva²,

Bielska³

et al. 2017

Molecules

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Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp3 character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp3 features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium.

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“…Wegen seiner ungewöhnlichen Struktur mit einem α‐Pyridon war es das Ziel mehrerer synthetischer Arbeiten . Dies führte bisher zu racemischen Synthesen durch Sarpong und Takayama sowie einer enantioselektiven Synthese durch letzteren . Das zentrale quartäre Stereozentrum wurde mit Eschenmoser‐Claisen‐, Diels‐Alder‐ bzw.…”

Section: Methodsunclassified

Eine Conia‐En‐artige Cyclisierung unter basischen Bedingungen ermöglicht die effiziente Synthese von (−)‐Lycoposerramin R

2016

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Eine enantioselektive Synthese des Lycopodium-Alkaloids Lycoposerramin Rw ird vorgestellt. Diese basiert auf einer basenvermittelten Cyclisierung, welched er Conia-En-Reaktion und ihren goldkatalysierten Varianten ähnelt. Mittels dieser Methode kçnnen Hydrindanone und andere mit einer exo-Methylengruppe funktionalisierte Ringsysteme bei Raumtemperatur ohne Metallkatalyse oder Substrataktivierung erhalten werden. Schema 1. Reaktionsentdeckung und ältere verwandte Reaktionen.

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Total synthesis of (±)-lycoposerramine-R, a novel skeletal type of Lycopodium alkaloid

Cited by 29 publications

References 41 publications

A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products

Eine Conia‐En‐artige Cyclisierung unter basischen Bedingungen ermöglicht die effiziente Synthese von (−)‐Lycoposerramin R

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