Synthesis of manoalide using a 1,2-metallate rearrangement

Pommier, Agnès; Kocieński, Philip

doi:10.1039/a701936j

Cited by 27 publications

(6 citation statements)

References 14 publications

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“…Although numerous syntheses of manoalide have been reported [70][71][72][73][74] including enantiospecific syntheses [75,76], low synthetic yields are not viable to sustain a large-scale market supply. Other than the elucidation of the antiinflammatory, diterpene glucoside pseudopterosin (18) [77][78][79] produced by symbiotic Symbiodinium sp.…”

Section: Marine Natural Products: Potential and Applicationsmentioning

confidence: 99%

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Dunlap

Jaspars²,

Hranueli³

et al. 2006

CMC

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Natural products from symbiotic or commensal associations between marine invertebrate and microbial organisms show exceptional promise as pharmaceuticals in many therapeutic areas. An economic and sustainable global market supply due to difficulty of synthesis is cited as the main obstacle for exploitation of these otherwise exciting marine bioactive compounds. Different strategies have been evoked to overcome this impediment as long-term harvesting of wild stocks from the environment is considered unsound, and other modes of production based on biosynthesis, such as aquaculture, have not yet been proven as reliable. One option is to clone the genes encoding the biosynthetic expression of a lead metabolite into a surrogate host suitable for industrial-scale fermentation. To facilitate this goal we are developing a universal system to clone and express genes responsible for biosynthesis of natural products from both eukaryotic and prokaryotic partners of marine symbioses. The ability to harness the complete meta-transcriptome of entire biosynthetic pathways is particularly valuable where the biogenesis of a target natural product occurring within a complex symbiotic association is unclear.

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Section: Marine Natural Products: Potential and Applicationsmentioning

confidence: 99%

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Dunlap

Jaspars²,

Hranueli³

et al. 2006

CMC

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“…Owing to the presence of two hemiacetal moieties at C24 and C25, manoalide is a mixture of diastereoisomers that undergo easy ring-chain tautomerism to the dialdehyde 2 . The absolute stereochemistry of the single remaining nonfluxional stereogenic center at C4 was ascertained by correlation with a synthetic derivative. , The first total synthesis of racemic manoalide was reported in 1985 by Katsumura and co-workers, and this was followed by six syntheses of the racemate − (including our own contribution). However, the first enantiospecific synthesis of (+)-(4 R )-manoalide evaded conquest until the concise asymmetric aldol approach of the Sodano group in 1999 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of (+)-Manoalide via a Copper(I)-Mediated 1,2-Metalate Rearrangement

et al. 2003

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An enantiospecific synthesis of the phospholipase A(2) inhibitor (+)-(4R)-manoalide is reported in which all 25 carbons of the sesterterpenoid skeleton are constructed from 3-furaldehyde, trimethylalane, oxirane, CO, beta-ionone, and propargyl bromide. The overall yield for the longest linear sequence (12 steps) is 12%. Key steps include (a) a zirconium-catalyzed carboalumination reaction to construct the C10-C11 trisubstituted alkene, (b) a Cu(I)-mediated 1,2-metalate rearrangement to construct the C6-C7 trisubstituted alkene, (c) a Sharpless kinetic resolution to secure the (4R)-stereochemistry, (d) generation of a 5-stannyl-2,3-dihydrofuran by Mo-catalyzed cycloisomerization of a homopropargylic alcohol, and (e) construction of the hydroxyfuranone ring by photooxidation of a silylfuran.

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“…Since then, manoalide can be considered a very useful pharmacological tool, being by far the most well-known phospholipase A 2 (PLA 2 ) inhibitor and several academic and industrial efforts have focused on developing analogues of manoalide to be used in anti-inflammatory therapy, it has been the target of a number of syntheses. [64][65][66][67][68] The absolute stereochemistries of the known anti-inflammatory agents manoalide was determined by comparison of their CD spectra with those of synthetic model compounds. 69 Cyclolinteinone 130, a sesterterpene from the sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase protein expression by blocking nuclear factor kappa B activation in J774 macrophages.…”

Section: Monocarbocyclic Sesterterpenoidsmentioning

confidence: 99%