A Highly Stereocontrolled Total Synthesis of (−)-Neodysiherbaine A

Takahashi, Keisuke; Matsumura, Takashi; Corbin, Graeme R. M.; Ishihara, Jun; Hatakeyama, Susumi

doi:10.1021/jo060410r

Cited by 32 publications

(14 citation statements)

References 18 publications

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“…Selective deprotection of the hydroxy groups in 12, 13 or products derived from one of these two can sometimes be challenging. [67,68] We thought that our metathesis precursor 10 would be well suited to access dihydropyrans or glycals with two orthogonal protecting groups at C4 and C6 position, for instance one benzyl ether and one silyl ether. While conventional silylation of 10 with a silyl halide or triflate would be an obvious solution, we pursued an alternative route that relies on the ability of ruthenium carbenes to activate Si-H bonds: for instance, Grubbs' catalysts are known to catalyze the hydrosilylation of alkynes [69][70][71] or the hydrogenation of alkenes with silanes.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

Schmidt

Biernat

2008

Eur J Org Chem

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Deoxy glycals can be synthesized from a mannitol-derived C 2 -symmetric diene diol by using the tandem RCM/isomerization approach. Incorporation of a ruthenium-catalyzed dehydrogenative silylation step into the reaction sequence is possible. Thus, an orthogonally protected 3-deoxy glycal results via a tandem RCM/hydrosilylation/isomerization sequence. All ruthenium-catalyzed steps of this tandem se-

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Section: Resultsmentioning

confidence: 99%

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

Schmidt

Biernat

2008

Eur J Org Chem

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“…Neodysiherbaine A ( 14 ) is a neurologically active compound that acts as a glutamate receptor agonist and shows epileptogenic properties. Contiguous to the isolation, the first synthesis has been carried out by the same research group [42] and several other syntheses followed [43–47]. …”

Section: Reviewmentioning

confidence: 99%

The direct oxidative diene cyclization and related reactions in natural product synthesis

Adrian¹,

Gross²,

Stark³

2016

Beilstein J. Org. Chem.

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SummaryThe direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (dia)stereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.

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“…The lactone was then treated with terminal iodides 18 and 19 [themselves prepared in three steps from (-)-epichlorohydrin (17)], via treatment with lithium diisopropylamide (LDA), to afford 22 and 23, respectively (as an inconsequential 3:1 mixture of diastereomers). Oxidation and regioselective elimination then provided butenolides 24 and steps [27][28][29]. We envisioned that the highly functionalized cis-THF core embedded within this natural product would pose an interesting challenge for the oxidative cyclization methodology, with the presented strategy providing an expeditious route to this amino acid [30].…”

Section: Sylvaticin and Cis-sylvaticinmentioning

confidence: 99%

“…This was accomplished by selective protection of the vicinal diol with 2,2-diethoxypropane to yield isopropylidene acetal 41, which was subsequently oxidized by the action of catalytic tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine N-oxide (NMO) to form lactam 42 in 82 % yield (via the intermediacy of a hemiaminal). Finally, exposure of 42 to aqueous HCl led to hydrolysis of the lactam and removal of the acetal, ester, and carbamate protecting groups to afford neodysiherbaine A (29); the overall sequence constituting a concise seven-step synthesis, in 24 % overall yield, representing the shortest synthesis of this natural product to date.…”

Section: Sylvaticin and Cis-sylvaticinmentioning

confidence: 99%

Oxidative cyclization for the synthesis of complex tetrahydrofuran-containing natural products

Pullin

Lipiński

Donohoe

2013

Pure and Applied Chemistry

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The osmium-catalyzed oxidative cyclization of vicinal diols onto proximal olefins to generate 2,5-cis-substituted tetrahydrofurans (THFs) has been exploited as the key step for the construction of several complex THF-containing natural products, namely, the annonaceous acetogenins cis-sylvaticin, sylvaticin, and the excitatory amino acid neodysiherbaine A. Recently modified conditions that employ a Lewis acid enable the cyclization to proceed under milder conditions, providing greater tolerance to acid-sensitive functional groups, as demonstrated in two of the syntheses. Flexibility for the construction of 2,5-trans-THFs was demonstrated in the synthesis of sylvaticin by utilization of an intramolecular hydride-shift sequence.Scheme 1 Osmium-catalyzed oxidative cyclization for the diastereoselective synthesis of cis-THFs and pyrrolidines. Scheme 6Hydride shift-intramolecular trapping for the synthesis of the trans-THF ring of sylvaticin.Scheme 7 Synthesis of the butenolide fragments: 26 for cis-sylvaticin and 24 for sylvaticin. Brought to you by | West Virginia University Authenticated Download Date | 11/19/14 6:26 PM 25. Necessary removal of the TBS group of 25 was then undertaken, by treatment with AcCl in MeOH, to afford 26.The end-game for the syntheses involved the union of the bis-THF and butenolide fragments, which in each case was achieved by CM (Scheme 8). For cis-sylvaticin, CM of bis-THF 9, using Grubbs II catalyst with 4 equiv of 26 (in order to avoid homodimerization of 9; the homodimer of 26 could be recovered and recycled into the reaction), gave the desired CM product 27 in good yield (79 %). The synthesis was completed in two final steps via diimide reduction of the disubstituted alkene and global removal of the three silyl protecting groups, thus completing the first total synthesis of cis-sylvaticin (2) in only 13 linear steps [24]. In a similar manner, for sylvaticin, CM of 16, using Grubbs-Hoveyda II and 24 (4 equiv), gave the CM product 28 in good yield (84 %). Conclusion of the synthesis, in line with that shown for cis-sylvaticin, gave sylvaticin (1), which again completed the first synthesis of the natural product via a 19-step linear sequence. In both cases the synthesis confirmed the structure of the natural products as originally reported by McLaughlin. NEODYSIHERBAINE ANeodysiherbaine A (29) is an excitatory amino acid, first isolated in 2001 by Sakai and co-workers from the Micronesian marine sponge Dysidea herbacea [25]. Neodysiherbaine A was found to be a potent convulsant and a highly selective agonist for kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors [26]. The first total synthesis was accomplished by Sakai in 26 steps [25], and three subsequent syntheses have been reported, which ranged between 15 to 23 R. D. C. PULLIN et al. Scheme 11Construction of the carbon skeleton via Negishi coupling.Scheme 12 Formation of the bicyclic core of neodysiherbaine A via oxidative cyclization.

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A Highly Stereocontrolled Total Synthesis of (−)-Neodysiherbaine A

Abstract: Neodysiherbaine A, a neuroexitotoxin occurring in a Micronesian marine sponge Dysidea herbacea, was synthesized from tri-O-acetyl-D-glucal with excellent stereocontrol. The method established enables us to obtain gram quantities of neodysiherbaine A and its related compounds.

Cited by 32 publications

References 18 publications

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

The direct oxidative diene cyclization and related reactions in natural product synthesis

Oxidative cyclization for the synthesis of complex tetrahydrofuran-containing natural products

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