Abstract
Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G(2)/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation.
MeSH Terms
Animals
Antineoplastic Agents/chemical synthesis,isolation & purification,pharmacology
Bridged Bicyclo Compounds, Heterocyclic/chemistry,pharmacology
Cell Cycle/drug effects
Lactones/chemical synthesis,chemistry,isolation & purification,pharmacology
Macrolides/chemical synthesis,chemistry,isolation & purification,pharmacology
Magnetic Resonance Spectroscopy
Molecular Structure
New Zealand
Paclitaxel/chemistry,pharmacology
Porifera/chemistry
Chemicals
Antineoplastic Agents
Bridged Bicyclo Compounds, Heterocyclic
Lactones
Macrolides
peloruside A
peloruside B
Paclitaxel
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Singh A Jonathan
Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand.
Xu Chun-Xiao
Xu Xiaoming
West Lyndon M
Wilmes Anja
Chan Ariane
Hamel Ernest
Miller John H
Northcote Peter T
Ghosh Arun K
References (29)
29 references, click to expand
-
Mycalamide D, a new cytotoxic amide from the New Zealand marine sponge Mycale species.
J Nat Prod. 2000 May;63(5):707-9
PMID: 10843597
-
Synthesis of the C12-C19 fragment of (+)-peloruside A through a diastereomer-discriminating RCM reaction.
Org Lett. 2005 May 26;7(11):2225-8
PMID: 15901175
-
An aldol-based synthesis of (+)-peloruside a, a potent microtubule stabilizing agent.
J Am Chem Soc. 2009 Mar 25;131(11):3840-1
PMID: 19249829
-
Enantioselective total synthesis of peloruside A: a potent microtubule stabilizer.
Org Lett. 2008 Mar 6;10(5):1001-4
PMID: 18247632
-
Synthesis of the C(1)-C(12) segment of peloruside A by an alpha-benzyloxymethyl ketone aldol strategy.
Org Lett. 2004 Mar 4;6(5):663-6
PMID: 14986944
-
Toward a total synthesis of peloruside A: enantioselective preparation of the C8-C19 region.
Org Lett. 2003 Dec 25;5(26):4959-61
PMID: 14682739
-
NMR determination of the bioactive conformation of peloruside A bound to microtubules.
J Am Chem Soc. 2006 Jul 12;128(27):8757-65
PMID: 16819869
-
Stereoselective synthesis of the C(1)-C(11) fragment of peloruside A.
Org Lett. 2005 Sep 1;7(18):3941-4
PMID: 16119937
-
Total synthesis and absolute configuration of the novel microtubule-stabilizing agent peloruside A.
Angew Chem Int Ed Engl. 2003 Apr 11;42(14):1648-52
PMID: 12698467
-
Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation.
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10460-5
PMID: 16030146
-
Peloruside A does not bind to the taxoid site on beta-tubulin and retains its activity in multidrug-resistant cell lines.
Cancer Res. 2004 Aug 1;64(15):5063-7
PMID: 15289305
-
Spatial and temporal variability of cytotoxic metabolites in populations of the New Zealand sponge Mycale hentscheli.
J Chem Ecol. 2005 May;31(5):1161-74
PMID: 16124239
-
Synthetic studies of microtubule stabilizing agent peloruside A: an asymmetric synthesis of C10-C24 segment.
Tetrahedron Lett. 2003 Oct 6;44(41):7659-7661
PMID: 30443085
-
Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity.
Cancer Res. 2002 Jun 15;62(12):3356-60
PMID: 12067973
-
Peloruside A synergizes with other microtubule stabilizing agents in cultured cancer cell lines.
Mol Pharm. 2007 Mar-Apr;4(2):269-80
PMID: 17397239
-
Studies for the synthesis of marine natural products.
Pure Appl Chem. 2009;81(2):181
PMID: 20126417
-
Peloruside A: a potent cytotoxic macrolide isolated from the new zealand marine sponge Mycale sp.
J Org Chem. 2000 Jan 28;65(2):445-9
PMID: 10813954
-
Improved procedure for the oxidative cleavage of olefins by OsO4-NaIO4.
Org Lett. 2004 Sep 16;6(19):3217-9
PMID: 15355016
-
Antitumor activity and mechanism of action of the novel marine natural products mycalamide-A and -B and onnamide.
Cancer Res. 1989 Jun 1;49(11):2935-40
PMID: 2720652
-
Toward the total synthesis of natural peloruside a: stereoselective synthesis of the backbone of the core.
Org Lett. 2004 Jan 8;6(1):71-4
PMID: 14703353
-
Toward the synthesis of peloruside a: fragment synthesis and coupling studies.
Org Lett. 2003 Feb 20;5(4):599-602
PMID: 12583779
-
Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D.
Angew Chem Int Ed Engl. 2009;48(27):5030-3
PMID: 19492384
-
A unique mode of microtubule stabilization induced by peloruside A.
J Mol Biol. 2008 May 16;378(5):1016-30
PMID: 18405918
-
An enantioselective synthesis of the C1-C9 segment of antitumor macrolide peloruside A.
Tetrahedron Lett. 2003 May 12;44(20):3967-3969
PMID: 30393410
-
Synergistic effects of peloruside A and laulimalide with taxoid site drugs, but not with each other, on tubulin assembly.
Mol Pharmacol. 2006 Nov;70(5):1555-64
PMID: 16887932
-
Strategies for the synthesis of the novel antitumor agent peloruside A.
Curr Opin Drug Discov Devel. 2008 Mar;11(2):251-71
PMID: 18283613
-
Total synthesis of (-)-2-epi-peloruside A.
Org Lett. 2008 Dec 18;10(24):5501-4
PMID: 19007239
-
Total synthesis of (+)-peloruside A.
Org Lett. 2005 Mar 31;7(7):1303-5
PMID: 15787492
-
L-selectride-mediated highly diastereoselective asymmetric reductive aldol reaction: access to an important subunit for bioactive molecules.
Org Lett. 2008 Nov 6;10(21):4811-4
PMID: 18831554