Total Synthesis of Swinholide A: An Exposition in Hydrogen-Mediated C–C Bond Formation

Shin, Inji; Hong, Suckchang; Krische, Michael J.

doi:10.1021/jacs.6b10645

Cited by 52 publications

(29 citation statements)

References 58 publications

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“…70 This methodology has proven to be highly versatile and readily scalable, enabling practical gram scale access to stereochemically complex building blocks for a wide range of highly complex polyketide natural products. 71–73 This efficiency has further enabled practical synthesis and testing of bryostatin derivatives, shedding new light on the relationship between potency and biological activity. 74 …”

Section: Many Customized Iterative Synthesis Methods Have Already Beementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

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Section: Many Customized Iterative Synthesis Methods Have Already Beementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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“…Among the related natural products, swinholide A and its monomeric precursor preswinholide A have been extensively studied toward the total synthesis; monumental achievements by Paterson and Nicolaou for swinholide A as well as by Nakata for preswinholide A were disclosed in the 1990s . Very recently, Krische and co‐workers reported the concise total synthesis of swinholide A in almost half the steps of the precedents . In the present total synthesis, a distinct strategy was used to install the appropriate stereochemistry at the initial stage of the fragment synthesis; the catalytic asymmetric direct aldol reaction effected by Cu I ‐chiral bidentate phosphine ligand complex using thioamide as the prenucleophile developed by us was the key transformation .…”

Section: Resultsmentioning

confidence: 99%

Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis

Cui

Morita

Ohno

et al. 2017

Chemistry A European J

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Four new macrolactones, leptolyngbyolides A-D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar structures of leptolyngbyolides were determined by extensive NMR studies, although complete assignment of the absolute configuration awaited the catalytic asymmetric total synthesis of leptolyngbyolide C. The synthesis took advantage of the catalytic asymmetric thioamide-aldol reaction using copper(I) complexed with a chiral bidentate phosphine ligand to regulate two key stereochemistries of the molecule at the outset. The present total synthesis demonstrates the utility of this reaction for the construction of complex chemical entities. In addition to the total synthesis, this work reports that leptolyngbyolides depolymerize filamentous actin (F-actin) both in vitro and in cells. Detailed biological studies suggest the probable order of F-actin depolymerization and apoptosis caused by leptolyngbyolides.

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“…Thet otal synthesis of the marine macrodiolide swinholide Ae nables juxtaposition of classical carbonyl addition chemistry and corresponding hydrogenative and transfer hydrogenative carbonyl additions (see Scheme 5). [19][20][21][22] Rather than utilizing ac hiral-auxiliary-based asymmetric aldol addition, as exemplified by Evans-type aldol reagents (Figure 1), [19] an asymmetric vinyl ketone-aldehyde reductive coupling catalyzed by ac hiral phosphinite-modified rhodium complex is employed. [24,25] Methyl vinyl ketone (MVK) is manufactured from acetone (1.56 10 6 tons yr À1 )a nd formaldehyde (8.7 10 6 tons yr À1 ), and is of commercial significance because of its frequent use as ac omonomer in photodegradable plastics.…”

Section: From Feedstocks To Building Blocks In Target-oriented Synthesismentioning

confidence: 99%

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

2019

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Use of abundant feedstock pronucleophiles in catalytic carbonyl reductive coupling enhances efficiency in target‐oriented synthesis. For such reactions, equally inexpensive reductants are desired or, ideally, corresponding hydrogen autotransfer processes may be enacted wherein alcohols serve dually as reductant and carbonyl proelectrophile. As described in this Minireview, these concepts allow reactions that traditionally require preformed organometallic reagents to be conducted catalytically in a byproduct‐free manner from inexpensive π‐unsaturated precursors.

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Total Synthesis of Swinholide A: An Exposition in Hydrogen-Mediated C–C Bond Formation

Cited by 52 publications

References 58 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

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