Stereoselective synthesis of a C1–C6 fragment of pinnatoxin A via a 1,4-addition/alkylation sequence

Nakamura, Seiichi; Kikuchi, Fumiaki; Hashimoto, Shunichi

doi:10.1016/j.tetasy.2008.04.013

Cited by 21 publications

(11 citation statements)

References 61 publications

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“…Although a similar transformation has been reported, 24 we found 14 to be unreactive to conditions reported by Bergdahl (Equation 5). Based upon these few experiments, it seems that TMSI may be required to promote 1,4-additions to chiral alkoxy crotonates and fumarates, although further work is needed in order to clarify the origin of the surprising lack of reactivity of such substrates toward conjugate addition.…”

Section: Resultssupporting

confidence: 87%

Diastereoselective addition of monoorganocuprates to a chiral fumarate: reaction development and synthesis of (−)-dihydroprotolichesterinic acid

2015

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Section: Resultssupporting

confidence: 87%

Diastereoselective addition of monoorganocuprates to a chiral fumarate: reaction development and synthesis of (−)-dihydroprotolichesterinic acid

2015

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“…The cycloaddition of 5 with α‐methylene lactone 6 19 in p ‐xylene at 160 °C in a sealed tube proceeded with complete regioselectivity to provide a mixture of four of the eight possible stereoisomers in a 45:27:18:10 ratio and a total yield of 83 %. Modest exo selectivity (72:28) was obtained as expected from known precedent,11b albeit with a poor diastereofacial selection (63:37).…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of Pinnatoxin A

Nakamura¹,

Kikuchi²,

Hashimoto³

2008

Angewandte Chemie

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Ein vertrauter Ring: Die rutheniumkatalysierte Cycloisomerisierung eines Enins, das durch exo‐selektive Diels‐Alder‐Reaktion mit einem α‐Methylenlacton als Dienophil erhalten worden war, erwies sich als hocheffektiv für den Aufbau des 27‐gliedrigen Carbocyclus von Pinnatoxin A. Die Totalsynthese wurde nach Bildung des siebengliedrigen cyclischen Imins durch selbstkatalysierte Dehydratisierung abgeschlossen.

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“…Although an asymmetric synthesis of (R)-10 exists, 11 we chose to develop a new route. This goal was ultimately achieved using Evans' auxiliary based conjugate addition of methylmagnesium bromide to oxazolidinone 14, 13 affording 15 with a diastereomeric ratio of 94:6 which could be improved to >99:1 with a single recrystallisation. Reductive cleavage of the oxazolidinone followed, and oxidation of the resultant alcohol with Dess-Martin periodinane (DMP) delivered the desired R-aldehyde 10 {[a] D 21 +10.4 (c 0.7, CHCl 3 ); (lit.…”

Section: Scheme 2 Synthesis Of Naphthalene Amidementioning

confidence: 99%

Total Synthesis of Danshenspiroketallactone

Chorley¹,

Chen²,

Furkert³

et al. 2011

Synlett

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Described herein is the first synthesis of the monobenzannulated 5,5-spiroketals danshenspiroketallactone and epi-danshenspiroketallactone, two components of the traditional Chinese medicine Danshen. Key features of the synthesis include a directed metallation-lactonisation sequence to install the isobenzofuranone moiety and an oxidative radical cyclisation to afford the monobenzannulated 5,5-spiroketal.Several diverse spiroketal-containing natural products have been isolated over the years, 1 but compounds of this class that contain aryl rings fused to the spiroketal moiety are relatively rare. 2 Two such examples are danshenspiroketallactone (1) and epi-danshenspiroketallactone (2), monobenzannulated 5,5-spiroketals isolated from Danshen, the traditional Chinese medicine consisting of dried roots of Chinese sage, Salvia miltiorrhiza that is used to treat renal failure, heart disease, and strokes. 3 Although 1 and 2 are epimeric at the spirocentre, subjecting 1 to prolonged acidic conditions has proven that 2 is a natural product and not an artefact of the isolation procedure. However, subjecting 2 to acidic conditions effects epimerization to 1, suggesting that some (or all) of 1 is produced during isolation and purification of the natural product(s) on silica gel. 4 Further analysis of this medicinal plant afforded cryptoacetalide (3) and epi-cryptoacetalide (5), 5 and the acetone extract of the closely related folk medicine Salvia aegyptiaca has been shown to contain 6-methylcryptoacetalide (4) and 6-methyl-epi-cryptoacetalide (6, 6 Figure 1).Due to an ongoing project aimed at identifying the compounds responsible for the therapeutic effect in traditional Chinese medicines, combined with our continued interest in the synthesis of benzannulated spiroketal natural products, 7 we decided to initiate a synthesis of danshenspiroketallactone (1). Furthermore, a recent total synthesis of cryptoacetalide (3, along with its epimer 5) 8 prompts us to disclose our own efforts in this area.Recently, we demonstrated that the oxidative radical cyclisation 9 of various benzofurans and chromans containing a hydroxyalkyl side chain could be used to construct a series of monobenzannulated spiroketals. 10 Encouraged by these promising model studies, we aimed to extend this methodology toward the synthesis of danshenspiroketallactone (1) and its retrosynthesis is based on this strategy (Scheme 1). Figure 1 Naturally occurring monobenzannulated 5,5-spiroketalsScheme 1 Retrosynthetic analysis of danshenspiroketallactone (1) We planned a late-stage spiroketalisation by oxidative radical cyclisation of alcohol 7 which in turn was to be obtained by lactonisation of intermediate 8. Directed metallation of naphthalene amide 9 followed by addition of Raldehyde 10 11 was proposed as the key carbon-carbon bond-forming step to deliver 8 (Scheme 1).Thus, our initial attention was aimed towards the synthesis of the two coupling partners 9 and 10. The synthesis of Me Me O O O Me R = H, cryptoacetalide (3) R = Me, 6-methylcryptoacetalide (4) R...

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Stereoselective synthesis of a C1–C6 fragment of pinnatoxin A via a 1,4-addition/alkylation sequence

Cited by 21 publications

References 61 publications

Diastereoselective addition of monoorganocuprates to a chiral fumarate: reaction development and synthesis of (−)-dihydroprotolichesterinic acid

Diastereoselective addition of monoorganocuprates to a chiral fumarate: reaction development and synthesis of (−)-dihydroprotolichesterinic acid

Total Synthesis of Pinnatoxin A

Total Synthesis of Danshenspiroketallactone

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