Selective Catalytic Oxidation of Substrates That Bind to Metalloporphyrin Enzyme Mimics Carrying Two or Four Cyclodextrin Groups and Related Metallosalens

Breslow, Ronald; Zhang, Xiaojun; Xu, Ruo; Maletic, and Milana; Merger, Roland

doi:10.1021/ja962295f

Cited by 126 publications

(90 citation statements)

References 26 publications

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“…The preparation of catalyst 1 has been described elsewhere (22). Substrate 2 was prepared by alkylation of 1,2-bis(4-hydroxyphenyl)ethane with 4-tert-butylphenylbromoacetate methyl ester, then hydrolysis to the diacid with lithium hydroxide.…”

Section: Methodsmentioning

confidence: 99%

“…We found that in water the porphyrins were able to bind olefins having hydrophobic end groups, and catalyze selective double bond epoxidation (22). The salens bound the substrates but did not catalyze the epoxidations, apparently because the geometry of the catalysts changes greatly when they go to the metallo-oxo intermediate structures.…”

mentioning

confidence: 94%

“…To extend this to substrates that do not coordinate to metal ions, we have recently synthesized metallosalens carrying two beta-cyclodextrin groups, and metalloporphyrins carrying two and four beta-cyclodextrin groups (22,23). We found that in water the porphyrins were able to bind olefins having hydrophobic end groups, and catalyze selective double bond epoxidation (22).…”

Section: Introductionmentioning

confidence: 99%

“…In our first study (21), metal binding groups were attached to the porphyrin or salen system, so that substrates carrying metal binding groups at both ends could coordinate to the catalysts through bridging metal ions. When two such coordinations occurred, to stretch the substrate across the central metal ion of the metalloporphyrin or metallosalen, a substrate double bond was catalytically epoxidized with turnover.To extend this to substrates that do not coordinate to metal ions, we have recently synthesized metallosalens carrying two beta-cyclodextrin groups, and metalloporphyrins carrying two and four beta-cyclodextrin groups (22,23). We found that in water the porphyrins were able to bind olefins having hydrophobic end groups, and catalyze selective double bond epoxidation (22).…”

mentioning

confidence: 99%

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An artificial cytochrome P450 that hydroxylates unactivated carbons with regio- and stereoselectivity and useful catalytic turnovers

Breslow

Huang

Zhang

et al. 1997

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

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143

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A catalyst has been synthesized comprising a manganese porphyrin carrying four beta-cyclodextrin groups. It catalyzes the hydroxylation of substrates of appropriate size carrying tert-butylphenyl groups that can hydrophobically bind into the cyclodextrin cavities. In one example as many as 650 catalytic turnovers are seen before the catalyst is oxidatively destroyed, and with a rate comparable to that of typical cytochrome P450 enzymes. In another example, a steroid derivative is regio-and stereoselectively hydroxylated at a single unactivated carbon atom, but more slowly and with fewer turnovers. The carbon attacked is not the most chemically reactive, and the selectivity is determined by the geometry of the catalyst-substrate complex. Nonbinding substrates are not reactive under the conditions used, and substrates with more f lexible binding geometries give more than a single product.Enzymes are remarkably selective catalysts. They bind a particular substrate out of a sea of available compounds in solution, then they perform a reaction at a particular position of the bound substrate (thus showing regioselectivity), often with stereoselectivity as well. The geometric control in the enzyme-substrate complex can completely dominate the normal reactivity of the substrate. For example, enzymes in the class cytochrome P450 can hydroxylate unactivated carbons in steroids while leaving much more reactive substrate positions, such as those in or next to double bonds, untouched (1-3). In these enzymes an oxygen atom becomes attached to the iron atom in the metalloporphyrin, and is then transferred to the substrate within the enzyme-substrate complex.Although it is of interest to learn how to mimic the great rate accelerations achieved in enzymatic catalysis, imitating the selectivity is even more important. For this reason, we have carried out studies over many years to learn how to use the geometric control typical of enzyme reactions in selectively functionalizing steroids and other substrates. In the earliest work, a benzophenone attached to a steroid was shown to perform selective photochemical functionalization of the substrate (4-11). In later work, a template attached to the substrate was able to direct free radical reactions to specific carbons because of the geometry of the template-substrate species; see refs. 12-14 for reviews. However, there were limitations to these methods.For one, the reagent or template was covalently attached to the substrate, so catalytic turnover was not possible. As a corollary of this, relatively simple reagents or templates were used-attached by a single flexible link-so the geometric control was not perfect. have shown that organization in a bilayer can be used to achieve hydroxylation of a steroid by a metalloporphyrin catalyst, but catalytic turnover was blocked by strong binding of the product. Grieco and colleagues (18-20) have also shown that a metalloporphyrin can hydroxylate a steroid in an intramolecular reaction if it is covalently attached, but again, this is no...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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An artificial cytochrome P450 that hydroxylates unactivated carbons with regio- and stereoselectivity and useful catalytic turnovers

Breslow

Huang

Zhang

et al. 1997

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

Self Cite

143

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“…The latter compounds were used for DNA photocleavage studies with the Pd(II) complex 69 exhibiting the best activity [171] . More details on other examples of A 4 -type glycoporphyrins (70-108) will be given below and are listed in Table 1 [172][173][174][175][176][177][178][179][180][181][182][183] . Pyrrole condensation reaction may also be employed for the preparation of dodecasubstituted porphyrins.…”

Section: A 4 -Type Porphyrinsmentioning

confidence: 99%

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Moylan¹,

Scanlan²,

Senge

2015

CMC

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Abstract:This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

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Epoxidation – Homogeneous

Merlau

Borg‐Breen

Nguyen

2002

Encyclopedia of Catalysis

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In this article, catalyst systems for homogeneous epoxidation are reviewed with an emphasis on reaction elements that are of foremost interest to synthetic chemists: catalyst systems, substrate scope, and selectivity. General mechanisms and reaction conditions for each catalyst system are discussed followed by more detailed summaries of the epoxidation of specific classes of olefins: unfunctionalized terminal olefins, cis‐disubstituted, trans‐disubstituted, tri‐ and tetrasubstituted olefins, functionalized olefins including allylic alcohols, and electron‐deficient olefins. Major classes of catalysts addressed are early transition metal‐peroxo forming catalysts (inclusive of the Sharpless titanium tartrate catalyst for the asymmetric epoxidation of allylic alcohols and MTO), metal‐oxo forming catalysts (such as metalloporphyrin and Jacobsen/Katsuki salen catalysts), dioxirane and oxaziridine catalysts, Lewis acid and lanthanide catalysts, phase‐transfer and polyamino acid catalysts, and finally sulfur ylide catalysts for the formation of epoxides from aldehydes. Dedicated to Professor K. Barry Sharpless on the occasion of his 60th birthday.

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Selective Catalytic Oxidation of Substrates That Bind to Metalloporphyrin Enzyme Mimics Carrying Two or Four Cyclodextrin Groups and Related Metallosalens

Cited by 126 publications

References 26 publications

An artificial cytochrome P450 that hydroxylates unactivated carbons with regio- and stereoselectivity and useful catalytic turnovers

An artificial cytochrome P450 that hydroxylates unactivated carbons with regio- and stereoselectivity and useful catalytic turnovers

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Epoxidation – Homogeneous

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