The Chemistry of Fumagillin<sup>1</sup>

Tarbell, D. S.; Carman, RM; Chapman, D.; Cremer, Sheldon E.; Cross, A. D.; Huffman, K. R.; Kunstmann, M. P.; McCorkindale, N.J.; McNally, James G.; Rosowsky, A.; Varino, F. H. L.; West, R. Lee

doi:10.1021/ja01475a029

Cited by 62 publications

(19 citation statements)

References 2 publications

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“…Groups of coupled protons which were separated by three quaternary carbons could be detected, and the assignments of these groups of protons were similar for 1 and 2. These facts suggested that 1 was 5>6-dihydroxy-4-(l ,2-epoxy-l ,5-dimethyl-4-hexenyl)-l -oxaspiro [2,5]octane. Next, we focused on the stereochemistry of the hydroxyl groups on the cyclohexane ring of 1.…”

Section: Structure Assignmentmentioning

confidence: 98%

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

et al. 1988

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Section: Structure Assignmentmentioning

confidence: 98%

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

et al. 1988

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“…6). 34,35 The epoxides can be chemically functionalized separately from the alkene and alcohol. Additionally, modications to the alkene and alcohol in later synthetic steps enable additional points for derivatization.…”

Section: Fumagillolmentioning

confidence: 99%

Natural products as starting points for the synthesis of complex and diverse compounds

2014

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Covering: up to 2013. Natural products and their derivatives are used as treatments for numerous diseases. Many of these compounds are structurally complex, possessing a high percentage of sp(3) hybridized carbons and multiple stereogenic centers. Due to the difficulties associated with the isolation of large numbers of novel natural products, lead discovery efforts over the last two decades have shifted toward the screening of less structurally complex synthetic compounds. While there have been many success stories from these campaigns, the modulation of certain biological targets (e.g. protein-protein interactions) and disease areas (e.g. antibacterials) often require complex molecules. Thus, there is considerable interest in the development of strategies to construct large collections of compounds that mimic the complexity of natural products. Several of these strategies focus on the conversion of simple starting materials to value-added products and have been reviewed elsewhere. Herein we review the use of natural products as starting points for the generation of complex compounds, discussing both early ad hoc efforts and a more recent systematization of this approach.

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“…The highly oxygenated natural product fumagillol ( 2 ) was chosen as the reactivity and proximity of the two epoxides present site(s) for potential chemistry, while the hydroxyl and alkene groups offer additional functionality for further diversification. Crude fumagillin ( 1 ), a natural product which is readily available from the fermentation broth of Aspergillus fumigates and can be hydrolyzed to fumagillol ( 2 ) (see Supplementary Information ), 19 , 20 , has generated significant interest as both a synthetic target 21 and for its anti-angiogenic properties. 22 – 24 We envisioned a series of tandem processes which could remodel fumagillol into novel chemotypes as dictated by either by catalyst or reaction partner choice.…”

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confidence: 99%

Remodelling of the natural product fumagillol employing a reaction discovery approach

et al. 2011

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In search for new biologically active molecules, diversity-oriented synthetic (DOS) strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as intriguing starting points for DOS, wherein stereochemically rich core structures may be reorganized into chemotypes which are distinctly different from the parent structure. Ideally such transformations should be general and involve few steps in order to be suited for library applications. With this objective in mind, the highly oxygenated natural product fumagillol has been successfully remodeled in several ways utilizing a reaction discovery-based approach. In reactions with amines, excellent regiocontrol in a bis-epoxide opening/cyclization sequence can be obtained by size-dependent interaction of an appropriate catalyst with the parent molecule, forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles can be further remodeled by cascade processes to afford either morpholinone or bridged 4,1-benzoxazepine-containing structures.

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The Chemistry of Fumagillin¹

Cited by 62 publications

References 2 publications

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

Natural products as starting points for the synthesis of complex and diverse compounds

Remodelling of the natural product fumagillol employing a reaction discovery approach

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The Chemistry of Fumagillin1

Cited by 62 publications

References 2 publications

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

Natural products as starting points for the synthesis of complex and diverse compounds

Remodelling of the natural product fumagillol employing a reaction discovery approach

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Product

Resources

About

The Chemistry of Fumagillin¹