Total Synthesis of (−)-Leuconicine A and B

Sirasani, Gopal; Andrade, Rodrigo

doi:10.1021/ol202056w

Cited by 70 publications

(28 citation statements)

References 13 publications

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“…Keywords: alkaloids · Barbier reaction · cascade reaction · indole · samarium diiodide [ Representative examples of Strychnos alkaloids. [9,10] Chem. Eur.…”

Section: Introductionmentioning

confidence: 99%

Towards the Core Structure of Strychnos Alkaloids Using Samarium Diiodide‐Induced Reactions of Indole Derivatives

Beemelmanns

Gross

Reißig

2013

Chemistry A European J

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This report describes the development of a first and second generation approach towards the synthesis of the ABCEG pentacyclic core structure of Strychnos alkaloids. First, we discuss a sequential approach applying a series of functional group transformations to prepare suitable precursors for cyclization reactions. These include attempts of samarium diiodide-induced cyclizations or a Barbier-type reaction of a transient lithium organyl, which successfully led to a tetracyclic key building block earlier used for the synthesis of strychnine. Secondly, we account our first steps towards the development of an atom-economical samarium diiodide-induced cascade reaction using "dimeric" indolyl ketones as cyclization precursors. In this context, we discuss plausible mechanisms for the samarium diiodide-induced cascade reaction as well as transformations of the obtained tetracyclic dihydroindoline derivatives.

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“…Keywords: alkaloids · Barbier reaction · cascade reaction · indole · samarium diiodide [ Representative examples of Strychnos alkaloids. [9,10] Chem. Eur.…”

Section: Introductionmentioning

confidence: 99%

Towards the Core Structure of Strychnos Alkaloids Using Samarium Diiodide‐Induced Reactions of Indole Derivatives

Beemelmanns

Gross

Reißig

2013

Chemistry A European J

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“…Anti-cancer agents aza-epothilones A–D v (see Fig. 1a), leuconicines A–B vi , natural products that can reverse multi-drug resistance, and immunosuppressant FR235222 vii are among entities the synthesis of which involves homoallylic amines. Enantioselective addition of an allyl group to an aldimine has thus been the subject of substantial scrutiny iv .…”

mentioning

confidence: 99%

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Silverio

Torker

Pilyugina

et al. 2013

Nature

201

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The discovery of new catalysts that can generate complex organic compounds via enantioselective transformations is central to advances in the life sciences;i for this reason, many chemists try to discover catalysts that can be used to produce chiral molecules with a strong preference for one mirror image isomer.ii The ideal catalyst should be devoid of precious elementsiii and should bring reactions to completion in a few hours using operationally simple procedures. In this manuscript, we introduce a set of small organic molecules that can catalyze reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which can be used to synthesize more complex, biologically active molecules. A distinguishing feature of this new catalyst class is the presence of a 'key' proton embedded within their structure. The catalyst is derived from the abundant amino acid valine and was prepared in large quantities in four steps using inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mol % catalyst in less than six hours at room temperature to generate products in >85% yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents render this advance vital to future progress in chemistry, biology and medicine.

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“…The use of reactive haloamides to form the C ring of aspidosperma and related alkaloids, by way of an intramolecular alkylation, is well established, having been first demonstrated by Heathcock in the synthesis of (±)-aspidospermidine. 19,20 Accordingly, we found that activation of the iodide with silver trifluoromethanesulfonate, along with added base, facilitated the desired spirocyclization, delivering the spirocyclic indolenine 13 . For formation of the E ring, we drew inspiration from Andrade’s recent exploits regarding a similar intramolecular aza-Morita–Baylis–Hillman reaction.…”

Section: Resultsmentioning

confidence: 92%

“…For formation of the E ring, we drew inspiration from Andrade’s recent exploits regarding a similar intramolecular aza-Morita–Baylis–Hillman reaction. 20,21 We were delighted to discover that addition of the highly nucleophilic and sterically undemanding trimethylphosphine to a solution of the indolenine 13 in benzene, with methanol as an additive, promoted the desired intramolecular aza-Morita–Baylis–Hillman reaction, yielding the desired pentacycle 19 in 80% yield over two steps. 22,23 …”

Section: Resultsmentioning

confidence: 99%

Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation

2012

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In this study we performed the total synthesis of the terpene indole alkaloid (+)-ibophyllidine through a pathway involving asymmetric phosphine catalysis, with our novel l-4-hydroxyproline–derived chiral phosphine mediating the key [3 + 2] annulation. Hydrogenation of the [3 + 2] adduct allowed the rapid formation of the stereochemically dense pyrrolidine ring of (+)-ibophyllidine in excellent yield with exceptionally high levels of both diastereo- and enantioselectivity. We constructed the remainder of the pentacyclic skeleton through an intramolecular alkylation and an intramolecular aza-Morita–Baylis–Hillman reaction.

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Total Synthesis of (−)-Leuconicine A and B

Cited by 70 publications

References 13 publications

Towards the Core Structure of Strychnos Alkaloids Using Samarium Diiodide‐Induced Reactions of Indole Derivatives

Towards the Core Structure of Strychnos Alkaloids Using Samarium Diiodide‐Induced Reactions of Indole Derivatives

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation

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