Synthesis of the sponge-derived plakortone series of bioactive compounds

Hayes, PY, Chow, S, Rahm, F, Bernhardt, PV, De Voss, JJ and Kitching, W (2010) Synthesis of the sponge-derived plakortone series of bioactive compounds. Journal of Organic Chemistry, 75 19: 6489-6501. doi:10.1021/jo101224w

Author Hayes, PY
Chow, S
Rahm, F
Bernhardt, PV
De Voss, JJ
Kitching, W
Title Synthesis of the sponge-derived plakortone series of bioactive compounds
Journal name Journal of Organic Chemistry   Check publisher's open access policy
ISSN 0022-3263
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1021/jo101224w
Volume 75
Issue 19
Start page 6489
End page 6501
Total pages 13
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2011
Language eng
Formatted abstract
The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex have provided a series of biologically active furanolactones the plakortones A-D (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of the plakortones is a sterically congested 2,6-dioxabicyclo[3. 3.0]octan-3-one moiety, the emblematic furanolactone core. This core is efficiently accessed by a palladium(II) mediated hydroxycyclization- carbonylation-lactonization cascade with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6) are now described which settle constitutional and stereochemical features in this group of secondary metabolites. Acquisition of plakortone D (4), the most effective activator of SR-Ca2+-pumping ATPase, utilized stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 29. A derived lactone aldehyde was then coupled with an independently generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond, carried through the sequence as a protected, stereodefined diol, was released therefrom by stereospecific syn-elimination via an orthoester derivative. In this way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E) configuration. Racemic plakortone E (5) was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 52 was assembled first. Plakortone C (3) resulted from a sequence commencing with (R)-(+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated primary alcohol 79 was converted by standard procedures to key enediol 89 which, with the Pd(II) protocol, afforded the major separable plakortones 90 and 91, with the former being identical with natural plakortone C (3). Very mild hydrogenation of 90 afforded a saturated plakortone, identical with natural plakortone F (6), thus establishing its structure and absolute stereochemistry. Available information on the stereoselective routes to plakortones E (5) and B (2) are also outlined, so that the constitution and absolute stereochemistry of plakortones B-F are now established. © 2010 American Chemical Society.
Keyword Absolute stereochemistry
Cyclic peroxides
Asymmetric dihydroxylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 10 Oct 2010, 00:03:26 EST