Synthesis of the securinega alkaloids (±)-norsecurinine and (±)-Nirurine from 3-hydroxypyridine.

Magnus, Philip; Rodríguez‐López, Julián; Mulholland, Keith R.; Matthews, Ian

doi:10.1016/s0040-4020(01)88027-3

Cited by 44 publications

(26 citation statements)

References 11 publications

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“…Following the protocol developed by Magnus et al, [27] (À)-norsecurinine (3) was treated with mCPBA in MeOH to chemoselectively afford N-oxide 20 (Scheme 4). The Noxide was then heated to reflux in xylene to initiate the sequential [2,3]-Meisenheimer and [1,3]-sigmatropic rearrangements to afford O-alkylhydroxylamine 21 in 90 % yield via intermediate 20 a.…”

mentioning

confidence: 99%

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

Wei¹,

Qiao²,

Liu³

et al. 2012

Angew Chem Int Ed

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confidence: 99%

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

Wei¹,

Qiao²,

Liu³

et al. 2012

Angew Chem Int Ed

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“…The diminished yields for 20 relative to our model (15) suggests that substrate 13 may possess a conformational bias that facilitates the reaction given that carbamate-protected piperidines generally prefer an axial orientation of C2 substituents when monosubstituted. From here, butenolide 20 was thus taken forward with a chemoselective hydroboration/oxidation sequence [21] furnishing the desired primary alcohol in 72 % yield, with 6 then accessed in 92 % yield by a one-pot methane sulfonate ester formation/N-Boc deprotection/cyclization sequence. In line with that supposition, heating of the reaction mixture to 50 8C during the slow addition process provided a notable yield increase to 47 %.…”

Section: Methodsmentioning

confidence: 99%

An Efficient Approach to the Securinega Alkaloids Empowered by Cooperative N‐Heterocyclic Carbene/Lewis Acid Catalysis

et al. 2013

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Dedicated to Professor Ronald Breslow on the occasion of his 82nd birthdayPlants of the Euphorbiaceae family are sources of several important collections of secondary metabolites, one being the securinega alkaloids (1-5 [2] and 7, Scheme 1). [1] These materials possess unique frameworks typically characterized by a bridged, tetracyclic substructure bearing a strained a,b,g,dunsaturated lactone motif (as in 1-5), though rearranged variants of such domains (such as in 7) [3] also exist. They also display intriguing biological activity; [4] for instance, securinine (1), the most abundant member of the family, is a potent GABA antagonist. Given these attributes, it is unsurprising that the synthetic community has devoted significant attention to this collection of compounds, [5] particularly to the challenges posed by the key shared domains within 1-5. Indeed, since the inaugural total synthesis of securinine (1) by Horii in 1966, [5a] several other successful and highly creative approaches for forging their fused bicyclic butenolide domains have been disclosed, efforts that include selenoxide eliminations, [5b,e,f,h,i,r] intramolecular Wittig olefinations, [5e,f,o,p,t-v] ring-closing metatheses, [5j-p,s,x] and alkylation of allylic bromides or mesylates. [5a,h,i-m,q,t-v,x] However, most of these strategies require multiple steps to execute, typically constituting the longest (and least efficient) portion of the overall route. Here, we disclose a new disconnection for this critical domain, one that uses a simple, acyclic starting material and a novel N-heterocyclic carbene (NHC)-catalyzed reaction [6,7] to forge the entire butenolide system in a single step. We highlight its utility through a concise and efficient synthesis of 3-deshydroxy-secuamamine A (6, an analog of 5 [2] and a structural isomer of 1) as well as the core framework of 1-3, and indicate preliminary results of the components necessary for its successful application in other contexts.Our generalized approach to quickly fashion the butenolide domains of the securinega class is shown in the lower half of Scheme 1, using target 6 for purposes of illustration. As indicated, we envisioned that this entire key motif could be accessed from an appropriate linear enynal precursor (8) through an intramolecular NHC-catalyzed homoenolate addition onto the lone ketone followed by lactonization.

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“…The reductive reactivity of the [(C 5 Me 5 ) 3 Ln] complexes can be rationalized by the fact that the C 5 Me 5 À ions are not well-stabilized electrostatically in these compounds due to the long LnÀC(C 5 Me 5 ) distances caused by steric congestion. If the redox reaction in Equation (1) is coupled to a one-electron metal-based reduction, for example, the U IV /U III couple [8] of uranium, then a complex such as [(C 5 Me 5 ) 3 U]…”

Section: Dedicated To the Memory Of Professor George Buchimentioning

confidence: 99%

A New Enantioselective Approach to Total Synthesis of the Securinega Alkaloids: Application to (−)-Norsecurinine and Phyllanthine

Han

LaPorte

Folmer

et al. 2000

Angewandte Chemie International Edition

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An inexpensive proline derivative and chiral control feature in the total synthesis of securinega alkaloids (-)-norsecurinine (1) and phyllanthine (2). Key steps in the synthesis of 1 include an intramolecular ketonitrile coupling and application of a radical-based generation of N-acylimines. The total synthesis of 2 utilizes a stereoselective imino Diels - Alder construction of the methoxypiperidine ring.

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Synthesis of the securinega alkaloids (±)-norsecurinine and (±)-Nirurine from 3-hydroxypyridine.

Cited by 44 publications

References 11 publications

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

An Efficient Approach to the Securinega Alkaloids Empowered by Cooperative N‐Heterocyclic Carbene/Lewis Acid Catalysis

A New Enantioselective Approach to Total Synthesis of the Securinega Alkaloids: Application to (−)-Norsecurinine and Phyllanthine

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