Epoxide-Opening Cascades Promoted by Water

Vilotijević, Ivan; Jamison, Timothy F.

doi:10.1126/science.1146421

Cited by 267 publications

(190 citation statements)

References 33 publications

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“…These exceedingly complex PKs contained one to three glycosylation sites. Even though 43A-B are presumably enzymatically cyclized, very recent experiments addressed a long-standing problem concerning the biosynthesis of such polyether ladders [421]. The solvent water was found to be critical in guiding ring size selectivity for the tandem epoxide ring openings initiated from a single tetrahydropyran template.…”

Section: Marine Fatty Acids Andmentioning

confidence: 99%

Biosynthesis and function of polyacetylenes and allied natural products

Minto

Blacklock

2008

Progress in Lipid Research

291

233

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Polyacetylenic natural products are a substantial class of often unstable compounds containing a unique carbon-carbon triple bond functionality, that are intriguing for their wide variety of biochemical and ecological functions, economic potential, and surprising mode of biosynthesis. Isotopic tracer experiments between 1960 and 1990 demonstrated that the majority of these compounds are derived from fatty acid and polyketide precursors. During the past decade, research into the metabolism of polyacetylenes has swiftly advanced, driven by the cloning of the first genes responsible for polyacetylene biosynthesis in plants, moss, fungi, and actinomycetes, and the initial characterization of the gene products.The current state of knowledge of the biochemistry and molecular genetics of polyacetylenic secondary metabolic pathways will be presented together with an up-to-date survey of new terrestrial and marine natural products, their known biological activities, and a discussion of their likely metabolic origins.

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Section: Marine Fatty Acids Andmentioning

confidence: 99%

Biosynthesis and function of polyacetylenes and allied natural products

Minto

Blacklock

2008

Progress in Lipid Research

291

233

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“…It is clear from the data in Table 1 that selectivity in the cyclization reactions under neutral aqueous conditions is very sensitive to the identity of the template and the size of the ring being formed (10)(11)(12). We were particularly surprised to find that a 1:1 mixture of products resulted from the seemingly minor change from 1a to 1b, which differ only by the replacement of an oxygen atom with a CH 2 group in the template (entries 1 and 2).…”

Section: Resultsmentioning

confidence: 79%

“…Up to this point, the importance of the template structure for selective endo cyclizations has been emphasized, yet as noted above, water was also implicated (10). Further investigation has revealed that selectivity is much less sensitive to the identity of the solvent than is the reaction rate (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Byers

Jamison

2013

Proc. Natl. Acad. Sci. U.S.A.

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Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins.entropic control | biomimetic G iven its simple structure and low molecular weight, water is a remarkably complex substance. Several landmark investigations (1) have revealed the ability of water to self-assemble to form sophisticated dynamic hydrogen bond networks, which accounts for its unusual properties, such as its high boiling point and high surface tension (2). Despite the unique properties that it offers and that nature has exploited, water is generally eschewed in synthetic chemistry largely because of chemical incompatibility with many commonly used reagents and the low aqueous solubility of many organic molecules coupled with the attendant assumption that homogeneity is required for reactivity. Although several important examples of remarkable reactivity have been documented for reactions carried out in water (3-5), on the surface of water (6, 7), or in micelles suspended in water (8, 9), utilization of the "biological solvent" in organic reactions remains uncommon.We became acutely aware of the remarkable properties of water when we discovered that neutral aqueous solutions of epoxy alcohol 1a underwent a spontaneous and selective "endo" cyclization reaction to form 6,6-fused bicyclic product 2a (Fig. 1) (10-12). Exceptional reactivity and selectivity were observed only when two criteria were satisfied: The substrate contained a sixmembered tetrahydropyran ring, and the solvent used was water at pH 7.0. These surprising results were counter to a set of general empirical rules put forth by Baldwin for cyclization reactions, which state that the smaller ring product resulting from what is commonly called an exo cyclization is favored for similar reactions (13). The tetrahydropyranol ring, therefore, appeared to "template" the endo cyclization pathway to form the larger ring product with water playing a critical yet heretofore unknown role.Moreover, 2a is a substructure found in a large family of natural products commonly referred to as the ladder polyethers (e....

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“…For example, a palladium-catalyzed tandem reaction resulted in multirings in one step (Scheme 12) (48). Another example is Jamison's synthesis of the core piece of ''ladder'' polyether marine natural products through a biomimetic cascade cyclization in neutral water (Scheme 13) (49).…”

Section: Synthesis Without Protectionsmentioning

confidence: 99%

Green chemistry for chemical synthesis

Trost²

2008

Proc. Natl. Acad. Sci. U.S.A.

808

360

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Green chemistry for chemical synthesis addresses our future challenges in working with chemical processes and products by inventing novel reactions that can maximize the desired products and minimize by-products, designing new synthetic schemes and apparati that can simplify operations in chemical productions, and seeking greener solvents that are inherently environmentally and ecologically benign.

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Epoxide-Opening Cascades Promoted by Water

Cited by 267 publications

References 33 publications

Biosynthesis and function of polyacetylenes and allied natural products

Biosynthesis and function of polyacetylenes and allied natural products

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Green chemistry for chemical synthesis

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