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

Kawa, Kohei; Hara, Akihiro; Ishikawa, Yuichi; Nishiyama, Shigeru

doi:10.3390/molecules16075422

Cited by 6 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following literature methodology, 31 to a solution of compound 10 (0.36 g, 1.0 mmol) dissolved in anhydrous THF (15 mL) under N 2 at 0 °C was added Et 3 N (0.79 mL, 5.7 mmol). The reaction was cooled to 0 °C, and pivaloyl chloride (0.19 mL, 1.5 mmol) was added dropwise.…”

Section: Methodsmentioning

confidence: 99%

“…The crude compound was purified through a short column of silica gel (MeOH/DCM, 1% isocratic elution) to give compound 10 as colorless crystals in 85% yield (1.78 (11). Following literature methodology, 30 to a solution of compound 10 (0.36 g, 1.0 mmol) dissolved in anhydrous THF (15 mL) under N 2 at 0 °C was added Et 3 N (0.79 mL, 5.7 mmol). The reaction was cooled to 0 °C, and pivaloyl chloride (0.19 mL, 1.5 mmol) was added dropwise.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of a Smoothened Cholesterol: 18,19-Di-nor-cholesterol

Mydock-McGrane¹,

Rath

Covey³

2014

J. Org. Chem.

View full text Add to dashboard Cite

Herein, we report the first synthesis of a demethylated form of cholesterol (18,19-di-nor-cholesterol), in which the C18 and C19 methyl groups of the β-face were eliminated. Recent molecular simulations modeling 18,19-di-nor-cholesterol have suggested that cholesterol’s opposing rough β-face and smooth α-face play necessary roles in cholesterol’s membrane condensing abilities and, additionally, that specific facial preferences are displayed as cholesterol interacts with different neighboring lipids and transmembrane proteins. Inspired by these poorly characterized biochemical interactions, an extensive 18-step synthesis was completed as part of a collaborative effort, wherein synthesizing a “smoothened” cholesterol analogue would provide a direct way to experimentally measure the significance of the β-face methyl groups. Starting from known perhydrochrysenone A, the synthesis of 18,19-di-nor-cholesterol was accomplished with an excellent overall yield of 3.5%. The use of the highly stereoselective Dieckmann condensation and the employment of Evans’ chiral auxiliary were both key to ensuring the success of this synthesis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Synthesis of a Smoothened Cholesterol: 18,19-Di-nor-cholesterol

Mydock-McGrane¹,

Rath

Covey³

2014

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Cytotoxic macrolides produced by members of the primarily benthic dinoflagellate genus Amphidinium, and hence called amphidinolides (Figures 4A-E), have shown hemolytic activity (Yasumoto et al, 1987), as well as evidence of cytotoxicity against cancer cell lines, and antifungal properties (Kobayashi et al, 1991;Bauer et al, 1995a,b;Kobayashi et al, 2002;Tsuda et al, 2007;Espiritu et al, 2017). Within the last decade, interest in the toxigenicity of this genus has increased because some species, namely the type species A. carterae Hulburt 1957 and members of the A. operculatum Claparède & Lachmann, 1859 species complex, are known to produce ichthyotoxic substances (Kobayashi et al, 1991;Satake et al, 1991;Tsuda et al, 1994;Bauer et al, 1995a,b). In most cases, bioactivity (and in higher doses toxicity) is assumed to be related to various polyketides and macrolides isolated from different species of the genus (Kobayashi et al, 1991;Bauer et al, 1995a,b;Kobayashi et al, 2002;Tsuda et al, 2007;Espiritu et al, 2017).…”

Section: Determination Of Toxin Composition Occurrence and Associatementioning

confidence: 99%

A Review on the Biodiversity and Biogeography of Toxigenic Benthic Marine Dinoflagellates of the Coasts of Latin America

2019

View full text Add to dashboard Cite

Many benthic dinoflagellates are known or suspected producers of lipophilic polyether phycotoxins, particularly in tropical and subtropical coastal zones. These toxins are responsible for diverse intoxication events of marine fauna and human consumers of seafood, but most notably in humans, they cause toxin syndromes known as diarrhetic shellfish poisoning (DSP) and ciguatera fish poisoning (CFP). This has led to enhanced, but still insufficient, efforts to describe benthic dinoflagellate taxa using morphological and molecular approaches. For example, recently published information on epibenthic dinoflagellates from Mexican coastal waters includes about 45 species from 15 genera, but many have only been tentatively identified to the species level, with fewer still confirmed by molecular criteria. This review on the biodiversity and biogeography of known or putatively toxigenic benthic species in Latin America, restricts the geographical scope to the neritic zones of the North and South American continents, including adjacent islands and coral reefs. The focus is on species from subtropical and tropical waters, primarily within the genera Prorocentrum, Gambierdiscus/Fukuyoa, Coolia, Ostreopsis and Amphidinium. The state of knowledge on reported taxa in these waters is inadequate and time-series data are generally lacking for the prediction of regime shift and global change effects. Details of their respective toxigenicity and toxin composition have only recently been explored in a few locations. Nevertheless, by describing the specific ecosystem habitats for toxigenic benthic dinoflagellates, and by comparing those among the three key regions-the Gulf of Mexico, Caribbean Sea and the subtropical and tropical Pacific coast, insights for further risk assessment of the global spreading of toxic benthic species is generated for the management of their effects in Latin America.

show abstract

“…[102,103] Even though it has moderate complexity only one total synthesis is reported so far. [104] Some synthetic studies have also been demonstrated. [105] Total synthesis of amphidinolide Q was commenced from meso-diol 56, that after several steps afforded aldehyde 57.…”

Section: -Membered Macrolidesmentioning

confidence: 99%

Applications of Wittig Reaction in the Total Synthesis of Natural Macrolides

et al. 2020

View full text Add to dashboard Cite

The Wittig reaction involves the synthesis of an alkene via the conversion of an aldehyde or ketone with the already generated ylide from a phosphonium salt. Significantly, when this important name reaction is employed the desired alkenes are constructed via a predictable manner, thus resultant particularly are useful in the total synthesis of natural products and synthetic complex organic compounds with definite geometric isomers, exhibiting diverse biological potencies. In this review we try to highlight the applications of the Wittig reaction as an efficient and attractive strategy in the total synthesis of macrolides from 2008 to 2020.

show abstract

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

Cited by 6 publications

References 10 publications

Synthesis of a Smoothened Cholesterol: 18,19-Di-nor-cholesterol

Synthesis of a Smoothened Cholesterol: 18,19-Di-nor-cholesterol

A Review on the Biodiversity and Biogeography of Toxigenic Benthic Marine Dinoflagellates of the Coasts of Latin America

Applications of Wittig Reaction in the Total Synthesis of Natural Macrolides

Contact Info

Product

Resources

About