Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction

Han, Jing‐Chun; Li, Fuzhuo; Li, Chuang‐Chuang

doi:10.1021/ja5084927

Cited by 83 publications

(59 citation statements)

References 72 publications

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“…This compares to 2 × 10 −4 % overall and 29 steps in the landmark Woodward synthesis of the compound (Woodward et al, 1954). This collective synthesis approach for plant compounds has subsequently been taken up by others (Ghavimi and Magnus, 2014;Han et al, 2014;.…”

Section: Organic Synthesismentioning

confidence: 91%

Discovery and resupply of pharmacologically active plant-derived natural products: A review

2015

Draw Science

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Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product- Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis.While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

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Section: Organic Synthesismentioning

confidence: 91%

Discovery and resupply of pharmacologically active plant-derived natural products: A review

2015

Draw Science

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“…sequence (e.g. conversion of 124 to 126) was a key step in the preparation of humulanolide natural products [436]. A macrocycle-forming RO-CM sequence using cyclobutenecarboxylates (e.g.…”

Section: )mentioning

confidence: 99%

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

Herndon

2016

Coordination Chemistry Reviews

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“…21 Thus protecting-group-free synthesis has become a hot research topic in recent years. [22][23][24] Considering mono-N'-substituted BIMs such as 4-6 are important lead compounds for PKC inhibitions and further chemical biology studies, we believe it makes sense to develop a general synthesis [25][26][27][28][29] of them all, based on arcyriarubin A with a protecting-group-free strategy, which requires the direct mono-N'-alkylation of arcyriarubin A. In this paper, we report the mono-N'-alkylation of arcyriarubin A and its application to the protecting-group-free synthesis of GF109203X.…”

Section: Introductionmentioning

confidence: 99%

Protecting-group-free synthesis of the bisindolylmaleimide GF109203X

Gao¹,

Jia²,

Li³

et al. 2015

Arkivoc

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The bisindolylmaleimide GF109203X is a highly selective inhibitor to Protein Kinase C (PKC) and has attracted much attention. However, its reported synthesis required protecting groups. In order to achieve a short and N-protecting-group-free synthesis of GF109203X, an investigation on N-alkylation of arcyriarubin A was carried out using different bases, solvents and equivalents of bromododecane. It is found that mono-N-alkylation and mono-N'-alkylation could be achieved respectively. Thus, a protecting-group-free synthesis of GF109203X was accomplished in 40% overall yield starting from indole. This work will lead to a short synthesis of mono-N'-alkylated arcyriarubins to accelerate drug discovery.

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Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction

Cited by 83 publications

References 72 publications

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Discovery and resupply of pharmacologically active plant-derived natural products: A review

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

Protecting-group-free synthesis of the bisindolylmaleimide GF109203X

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