Assembly of the Isoindolinone Core of Muironolide A by Asymmetric Intramolecular Diels–Alder Cycloaddition

Flores, B. S.; Molinski, Tadeusz F.

doi:10.1021/ol201461n

Cited by 19 publications

(14 citation statements)

References 27 publications

(22 reference statements)

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“…A first biological evaluation showed that 204 displays antifungal activity. However, only 90 µg could be isolated and further biological screening was not possible [151]. Several sponge-derived macrolides have proven to be effective cytotoxic agents [152–153] and one could speculate that muironolide A ( 204 ) shares this potential.…”

Section: Reviewmentioning

confidence: 99%

“…Several sponge-derived macrolides have proven to be effective cytotoxic agents [152–153] and one could speculate that muironolide A ( 204 ) shares this potential. A first attempt to access 204 in the laboratory was reported by Molinski shortly after the isolation (Scheme 26) [151]. Coupling of the dienophile precursor 198 with sorbic acid ( 199 ) gave a tertiary amide, which was converted to 200 via a reduction–oxidation sequence.…”

Section: Reviewmentioning

confidence: 99%

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The chemistry of isoindole natural products

Speck¹,

Magauer²

2013

Beilstein J. Org. Chem.

305

163

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SummaryThis review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

The chemistry of isoindole natural products

Speck¹,

Magauer²

2013

Beilstein J. Org. Chem.

305

163

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“…The low-yield isolation of 32 necessitates total synthesis in order to address the resupply challenge and allow for further biomedical investigation. Flores & Molinski (2011) have recently reported the synthesis of the isoindolinone core of 32, and further investigations are underway.…”

Section: Alkaloidmentioning

confidence: 99%

An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

Vaske

Crews

2013

Bioactive Compounds From Marine Foods

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In this chapter we discuss a selection of structurally diverse marine-derived small molecules (MDSMs) with potent and/or specific bioactivity and analyze their biomedical applications. The compounds included have been isolated either from marine macroorganisms, including sponges, ascidians (tunicates), bryozoans, and molluscs, or from microorganisms, such as bacteria and fungi. Our inquiry begins with a look back in time at a selection of important marine natural products, with particular focus on compounds in the clinical pipeline. The chapter continues with an analysis of a biosynthetically diverse assortment of 22 MDSMs and their structural elements of atom and stereochemical diversity. Entries have been divided into five biosynthetic classes: terpene, polyketide, alkaloid, depsipeptide, and polyketide-peptide. Enormous structural variety is represented by the marine natural products treated herein. The compounds selected can be considered to represent case examples of significant biomolecules with positivity and, in some cases, potent bioactivity accompanied by an unusual mechanism of action. Overview of known compounds, highlighting molecules of significanceThe ocean covers more than 70% of the earth's surface and is home to exceptional biodiversity: more than one million marine species and an estimated one billion different kinds of marine microbe (Census of Marine Life Press Release 2010). We and others firmly believe that MDSMs represent a continuing resource for tools important in cell biology research and in the design of the next-generation leads for drug discovery and development. The record to date firmly illustrates that the structures of natural products continue to be invaluable in expanding pharmacophore structural space. For example, Newman and Cragg recently provided a detailed analysis of the last 30 years of natural products in drug discovery, wherein they contended that, "Nature's 'treasure trove of small molecules' remains to be explored, particularly from the marine and microbial environments" (Newman & Cragg 2012).

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“…4,5 Isoindolinone 1 is closely related to the heterocyclic subunit of the natural product and contains most of its structural information. At the onset, our synthetic planning has been informed by conformational analysis of the bicyclic ring system.…”

mentioning

confidence: 99%

“…The attempted rearrangement of the double bond in an intermediate similar to 2 into conjugation with the lactam carbonyl group was found to be problematic. 5 …”

mentioning

confidence: 99%

An Efficient Synthesis of the Fully Elaborated Isoindolinone Unit of Muironolide A

2013

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Assembly of the Isoindolinone Core of Muironolide A by Asymmetric Intramolecular Diels–Alder Cycloaddition

Abstract: The hexahydro-1H-isoindolin-1-one core of muironolide A was prepared by asymmetric intramolecular Diels Alder cycloaddition using a variant of the MacMillan organocatalyst which sets the C4,C5 and C11 stereocenters.

Cited by 19 publications

References 27 publications

The chemistry of isoindole natural products

The chemistry of isoindole natural products

An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

An Efficient Synthesis of the Fully Elaborated Isoindolinone Unit of Muironolide A

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