The Galbulimima alkaloids - AK Kalesse - Leibniz Universit¤t
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The Galbulimima alkaloids a new frontier in alkaloid synthesis Kalesse group seminar, 2012/11/05 Olaf Hartmann, Leibniz Universität Hannover, Institut für Organische Chemie, AK Kalesse
Transcript of The Galbulimima alkaloids - AK Kalesse - Leibniz Universit¤t
The Galbulimima alkaloids a new frontier in alkaloid synthesis Kalesse group seminar, 2012/11/05
Olaf Hartmann, Leibniz Universität Hannover, Institut für Organische Chemie, AK Kalesse
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contents
Introduction
Classification
Syntheses of himbacine (class I alkaloid) core by several groups
Syntheses of GB 13 and himgaline (class III) by several groups
Synthesis of himandrine (class II)
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Galbulimima alkaliods
Isolated from the bark of the rain forest trees
Galbulimima belgraveana (Papua New Guinea, Indonesia)
and G. baccata (Northern Australia) (white magnolia)
(formerly Himantantra belg.)
Traditional medicine: chewed bark to induce dream-like state, powdered bark
w/ tobacco and ginger against hair lice, swallowed against abdominal pain
Several alkaloids isolated from end-1940s on,
w/ a variety of biological activities,
most important member Himbacine (1): potent
muscarinic antagonist & possible Alzheimer candidate,
potential derivative in clinical trial as antithrombotic
agent
U. Rinner, C. Lentsch, C. Aichinger, Synthesis 2010, 22, 3763; D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
S. Chackalamannil et al., J. Med. Chem. 2005, 48, 5884; S. Chackalamannil et al., Expert Opin. Ther. Pat. 2006, 16, 493.
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Classification
Class I: 7 members,
tetracyclic lactones
Class II: 15 members,
highly oxigenated hexacyclic esters
Class III: four members,
penta/hexacyclic bases of low oxygen content
Class IV:
four members,
miscellenous
or structure
unknown
D. Bhattacharyya, Tetrahedron 2011, 67, 5525, and references therein
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Syntheses of (+)-himbacine ABC core
D. J. Hart et al., JACS 1995, 117, 9369; J. Org. Chem. 1997, 62, 5023; J. E. Baldwin et al., Org. Lett. 2005, 7, 585; Tetrahedron 2005, 61, 11649.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
Hart
Baldwin
both use an
IMDA
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Syntheses of (+)-himbacine ABC core
Chakalamannil
S. Chakalamannil et al., JACS 1996, 118, 9812.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 (Mander)
L. N. Mander et al., JACS 2003, 125, 2400; L. N. Mander et al., Aust. J. Chem. 2010, 63, 742.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 (Mander)
L. N. Mander et al., JACS 2003, 125, 2400; L. N. Mander et al., Aust. J. Chem. 2010, 63, 742.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 (Sarpong)
R. Sarpong et al., JACS 2009, 131, 13244.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 (Movassaghi)
M. Movassaghi et al., JACS 2006, 128, 8126.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 (Movassaghi)
M. Movassaghi et al., JACS 2006, 128, 8126.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 & himgaline (Ma)
D. Ma et al., Angew. Chem. Int. Ed. 2010, 49, 5887.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of GB 13 & himgaline (Ma)
D. Ma et al., Angew. Chem. Int. Ed. 2010, 49, 5887.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of himandrin (Movassaghi)
M. Movassaghi, M. Tjandra, J. Qi, JACS 2009, 131, 9648.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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Synthesis of himandrin (Movassaghi)
M. Movassaghi, M. Tjandra, J. Qi, JACS 2009, 131, 9648.
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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The end
That‘s all, folks!
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