The Galbulimima alkaloids - AK Kalesse - Leibniz Universität

16 Pages·2012·1.28 MB·English

by  Olaf Hartmann

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
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)

slide 2
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.
slide 3
S. Chackalamannil et al., J. Med. Chem. 2005, 48, 5884; S. Chackalamannil et al., Expert Opin. Ther. Pat. 2006, 16, 493.
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
slide 4
Syntheses of (+)-himbacine ABC core

Hart

Baldwin

both use an
IMDA
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.
slide 5
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
Syntheses of (+)-himbacine ABC core

Chakalamannil
S. Chakalamannil et al., JACS 1996, 118, 9812.
slide 6
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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.
slide 7
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
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.
slide 8
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
Synthesis of GB 13 (Sarpong)
R. Sarpong et al., JACS 2009, 131, 13244.
slide 9
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.
Synthesis of GB 13 (Movassaghi)
M. Movassaghi et al., JACS 2006, 128, 8126.
slide 10
D. Bhattacharyya, Tetrahedron 2011, 67, 5525.