An efficient and enantioselective total synthesis of naturally occurring L-783277

Choi, Hwan Geun; Son, Jung Beom; Park, Dong Sik; Ham, Young Jin; Hah, Jung Mi; Sim, Taebo

doi:10.1016/j.tetlet.2010.07.122

Cited by 16 publications

(20 citation statements)

References 30 publications

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“…The synthetic strategies used for both segments may enable the synthesis of analogs. The stereogenic centers were introduced via asymmetric reactions, which can produce another enantiomer by exchanging the auxiliary group or catalyst, with the exception of the C11 center: in this case the opposite ( R )-enantiomer would be produced using ( R )-glyceraldehyde acetonide, derived from D-mannitol [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

et al. 2011

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β-Hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

et al. 2011

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“…We investigated the effects of a structural nature of L-783277 ( 4 ) on kinase inhibitory activities in three subsequent researches [ 52 , 53 , 54 ]. In an effort to expand our MEK kinase program and to conduct a detailed SAR study with L-783277 ( 4 ) derivatives, we developed an efficient synthetic route toward L-783277 ( 4 ) [ 54 ].…”

Section: Biological Activities and Chemistry Of Natural And Synthementioning

confidence: 99%

“…In 2010, our group successfully accomplished efficient and enantioselective total synthesis of L-783277 ( 4 ), based on convergent assembly of one aromatic unit and two chiral building blocks with efficient orthogonal protection-deprotection strategy [ 53 ]. Three key steps composed of olefin cross metathesis, addition of acetylene derivative to aldehyde, and Yamaguchi macrolactonization were subsequently employed to construct the framework of L-783277 ( 4 ) ( Scheme 23 ).…”

Section: Biological Activities and Chemistry Of Natural And Synthementioning

confidence: 99%

“…The propargylic alcohol 167 was prepared from 166 using the same sequence of reactions described in our previous report [ 53 ]. Lindlar hydrogenation, deprotection, and saponification generated seco acid 168 , which was cyclized under Mitsunobu condition to deliver a diastereomeric mixture of 169 ( Scheme 37 ).…”

Section: Biological Activities and Chemistry Of Natural And Synthementioning

confidence: 99%

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Natural and Synthetic Lactones Possessing Antitumor Activities

Kim

Sengupta

Sim

2021

IJMS

Self Cite

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Cancer is one of the leading causes of death globally, accounting for an estimated 8 million deaths each year. As a result, there have been urgent unmet medical needs to discover novel oncology drugs. Natural and synthetic lactones have a broad spectrum of biological uses including anti-tumor, anti-helminthic, anti-microbial, and anti-inflammatory activities. Particularly, several natural and synthetic lactones have emerged as anti-cancer agents over the past decades. In this review, we address natural and synthetic lactones focusing on their anti-tumor activities and synthetic routes. Moreover, we aim to highlight our journey towards chemical modification and biological evaluation of a resorcylic acid lactone, L-783277 (4). We anticipate that utilization of the natural and synthetic lactones as novel scaffolds would benefit the process of oncology drug discovery campaigns based on natural products.

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“…[36] The retrosynthetic strategy was outlined in Scheme 5. [36] The retrosynthetic strategy was outlined in Scheme 5.…”

Section: Synthetic Strategies For Cis-enone Ralsmentioning

confidence: 99%

Cis-enone Resorcylic Acid Lactones (RALs) as Irreversible Protein Kinase Inhibitors

Wei¹,

Jian-hua²,

Li³

et al. 2012

CPD

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Resorcylic acid lactones (RALs) constitute a group of polyketide natural products with a large macrocyclic ring fused to resorcylic acid. Despite distinct core scaffold from all marketed kinase inhibitors, RALs bearing a cis-enone moiety have recently shown irreversible yet selective inhibition on a subset of kinases along the MAPK signaling pathway such as MEK, ERK and TAK1. The biochemical and structural studies have demonstrated that the cis-enone RALs can inhibit kinase activity by forming a covalent Michael adduct with an adequately positioned cysteine residue in the ATP binding pocket. This review discusses the mechanism of action, synthetic strategies, and structure-activity relationships (SARs) of cis-enone RALs. It is anticipated that design, synthesis and evaluation of cis-enone RALs analogs will diversify the chemical space of kinase inhibitors and facilitate the development of new leads for the treatment of various diseases such as cancer and inflammatory disorders.

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An efficient and enantioselective total synthesis of naturally occurring L-783277

Cited by 16 publications

References 30 publications

Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

Natural and Synthetic Lactones Possessing Antitumor Activities

Cis-enone Resorcylic Acid Lactones (RALs) as Irreversible Protein Kinase Inhibitors

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