Total Synthesis of FR901464, an Antitumor Agent that Regulates the Transcription of Oncogenes and Tumor Suppressor Genes

Albert, Brian J.; Sivaramakrishnan, Ananthapadmanabhan; Naka, Tadaatsu; Koide, Kazunori

doi:10.1021/ja058216u

Cited by 89 publications

(41 citation statements)

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“…γ-Hydroxy-α,β-acetylenic esters are precursors for γ-hydroxy-α,β-alkenyl esters,8 cis- 9,10 and trans-γ-oxo-α,β-alkenyl esters 9,11,12. In our laboratory, γ-hydroxy-α,β-alkenyl ester played a pivotal role in the synthesis of FR901464 13–15. While studying the scope of zirconium/silver-promoted alkynylation of aldehydes and ketones, we found the interesting reactivity of 2-pyridinecarboxaldehyde toward γ-hydroxy-α,β-acetylenic esters, which is the subject of this communication.…”

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confidence: 89%

Cyclic acetal formation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters

Osman

Koide

2008

Tetrahedron Letters

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A new transformation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters to form highly functionalized cyclic acetals was discovered. This transformation proceeds under very mild conditions without any additives and is promoted by the basic nature of the pyridine ring.Electron-deficient propargylic alcohols such as γ-hydroxy-α,β-alkenyl esters are important intermediates in organic synthesis due to their potential for further functionalization. [1][2][3][4] As such, development of new synthetic methodologies toward the preparation of these important synthetic intermediates is of interest to many research groups including ours. For example, we showed that highly functionalized γ-hydroxy-α,β-acetylenic esters could be prepared by the coupling of aldehydes, ketones, or epoxides with silver acetylides in the presence of Cp 2 ZrCl 2 and AgOTf. 5,6 The Trost group later developed an enantioselective method to prepare these compounds. 7 γ-Hydroxy-α,β-acetylenic esters are precursors for γ-hydroxy-α,β-alkenyl esters, 8 cis-9,10 and trans-γ-oxo-α,β-alkenyl esters. 9,11,12 In our laboratory, γ-hydroxy-α,β-alkenyl ester played a pivotal role in the synthesis of FR901464. [13][14][15] While studying the scope of zirconium/silver-promoted alkynylation of aldehydes and ketones, we found the interesting reactivity of 2-pyridinecarboxaldehyde toward γ-hydroxy-α,β-acetylenic esters, which is the subject of this communication.In our efforts to develop zirconium/silver-promoted alkynylations of functionalized carbonyl compounds with silver acetylides, 6 the coupling between 2-pyridinecarboxaldehyde (1) and Ag-C≡C-CO 2 Me (2) in the presence of Cp 2 ZrCl 2 gave an intractable mixture (Scheme 1a). We hypothesized that the expected product 3 could react with 1, thereby producing the mixture. To test this hypothesis, a mixture of 4 and 1 (1:1, 0.3 M each) was stirred at 23 °C in CH 2 Cl 2 for 4 d (Scheme 1b). These reaction conditions produced the highly functionalized product 5 in 65% yield, whose structure was confirmed by X-ray crystallography (Figure 1). Interestingly, compound 4 did not react with either 3-or 4-pyridinecarboxyaldehyde. Similar compounds were produced by Evans et al. by using alcohol substrates and potassium t-butoxide with an aldehyde to form 6-membered cyclic acetals. 16 Another work to form very similar 6-membered ring 1,3-dioxan-4-ylidenes was accomplished by Kwon et al. under phosphine catalysis. 17 These examples demonstrate the importance of cyclic acetals in organic synthesis.© 2008 Elsevier Ltd. All rights reserved. *Corresponding author. Tel.: +1-412-624-8767; fax: +1-412-624-8611; e-mail: koide@pitt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process...

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confidence: 89%

Cyclic acetal formation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters

Osman

Koide

2008

Tetrahedron Letters

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“…7). 21a Especially challenging was the final connection of two fragments of this antitumor agent via diene–ene CM. The fragile nature of alkene fragment B (thermal decomposition at ≥47°C) precluded more forcing reaction conditions.…”

Section: Electron‐withdrawing Group (Ewg)‐substituted Hoveyda–grubbs mentioning

confidence: 99%

“…The fragile nature of alkene fragment B (thermal decomposition at ≥47°C) precluded more forcing reaction conditions. Gratifyingly, despite the absence of any protecting groups ,21b the application of the highly active catalyst 6 at room temperature furnished FR901464 in 40% yield (51% based on recovered diene) 21a…”

Section: Electron‐withdrawing Group (Ewg)‐substituted Hoveyda–grubbs mentioning

confidence: 99%

Thirdhand Smoke Identified as Potent, Enduring Carcinogen

Dreyfuss¹

2010

CA: A Cancer Journal for Clinicians

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“…No.2663, Koide applied Carreira's method to construct a propargylic alcohol intermediate (Scheme 39) [71]. Since Carreira's method is not…”

Section: αβ-Alkenoic Acids and Estersmentioning

confidence: 99%

γ-Hydroxy-α,β-acetylenic esters: asymmetric syntheses and applications

Gao

2010

Sci. China Chem.

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γ-Hydroxy-α,β-acetylenic esters are versatile synthetic precursors to many organic compounds. This paper reviews the synthesis of chiral γ-hydroxy-α,β-acetylenic esters by asymmetric reduction of γ-oxo-α,β-acetylenic esters, enantioselective addition to aldehydes in the presence of chiral catalysts, and diastereoselective addition to chiral aldehydes. The preparation of racemic γ-hydroxy-α,β-acetylenic esters is also included. Examples are provided for the application of γ-hydroxy-α,β-acetylenic esters in organic synthesis.γ-hydroxy-α,β-acetylenic ester, asymmetric, enantioselective, diastereoselective

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Total Synthesis of FR901464, an Antitumor Agent that Regulates the Transcription of Oncogenes and Tumor Suppressor Genes

Cited by 89 publications

References 15 publications

Cyclic acetal formation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters

Cyclic acetal formation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters

Thirdhand Smoke Identified as Potent, Enduring Carcinogen

γ-Hydroxy-α,β-acetylenic esters: asymmetric syntheses and applications

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