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  Total Synthesis of Berkelic Acid

Snaddon, T. N., Buchgraber, P., Schulthoff, S., Wirtz, C., Mynott, R., & Fürstner, A. (2010). Total Synthesis of Berkelic Acid. Chemistry – A European Journal, 16(40), 12133-12140. doi:10.1002/chem.201001133.

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[280]SI.pdf (Supplementary material), 2MB
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2010
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Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim
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 Creators:
Snaddon, Thomas N.1, Author              
Buchgraber, Philipp1, Author              
Schulthoff, Saskia1, Author              
Wirtz, Cornelia2, Author              
Mynott, Richard2, Author              
Fürstner, Alois1, Author              
Affiliations:
1Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445584              
2Service Department Mynott (NMR), Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445627              

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Free keywords: anticancer agents; enzyme inhibitors; natural products; spiro compounds; total synthesis
 Abstract: A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant. Access to fragment 25 takes advantage of the Collum–Godenschwager variant of the ester enolate Claisen rearrangement, which clearly surpasses the classical Ireland–Claisen procedure in terms of diastereoselectivity. Although it is possible to elaborate 32 into the target without any additional manipulations of protecting groups, a short detour consisting in the conversion of the phenolic –OH into the corresponding TBS-ether is beneficial. It tempers the sensitivity of the compound toward oxidation and hence improves the efficiency and reliability of the final stages. Orthogonal ester groups for the benzoate and the aliphatic carboxylate terminus of the side chain secure an efficient liberation of free berkelic acid in the final step of the route.

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Language(s): eng - English
 Dates: 2010-06-172010-09-172010-10-25
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 537986
DOI: 10.1002/chem.201001133
ISI: 000284060200015
 Degree: -

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Title: Chemistry – A European Journal
  Other : Chem. – Eur. J.
  Other : Chem. Eur. J.
Source Genre: Journal
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Publ. Info: Weinheim, Germany : VCH Verlagsgesellschaft
Pages: - Volume / Issue: 16 (40) Sequence Number: - Start / End Page: 12133 - 12140 Identifier: ISSN: 0947-6539
CoNE: https://pure.mpg.de/cone/journals/resource/954926979058