Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4

Laurent De Backer; Eduard Dolušić; Stéphane Collin; Steve Lanners

Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4

Laurent De Backer, Eduard Dolušić, Stéphane Collin, Steve Lanners

Research output: Contribution to conference › Poster

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Abstract

Combretastatin A-4 (1) is a natural product isolated from the South African bushwillow tree Combretum caffrum. It is endowed with a powerful inhibitory activity on microtubule formation as well as a related antiangiogenic activity.[1-2] As such, 1 has a strong potential in the anticancer therapy, prompting the development of new derivatives.[3-6] We have turned our attention to the design of a synthetic procedure for 1 performed entirely in flow, which should enable continuous and rapid production of this useful compound and its derivatives in significant quantities.
Presented in this poster is a crucial step in this synthetic strategy - a selective semi-reduction of the triple bond of an alkyne precursor to the Z-double bond in the final product. The Lindlar-type hydrogenation in flow has been described only scarcely and for products typically more stable than Z-stilbenes.[7] We therefore set out to explore this technique and decided to expand it to a wider range of structurally various alkynes.

References
[1] C. M. Lin, S. B. Singh, P. S. Chu, R. O. Dempcy, J. M. Schmidt, G. R. Pettit, E. Hamel, Mol. Pharmacol. 1988, 34, 200.
[2] D. J. Kerr, E. Hamel, M. K. Jung, B. L. Flynn, Bioorg. Med Chem. 2007, 15, 3290.
[3] M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin, F. Menichini, Curr. Med. Chem. 2011, 18, 3035.
[4] Y. S. Shan, J. Zhang, Z. Liu, M. Wang, Y. Dong, Curr. Med. Chem. 2011,18, 523.
[5] C. Spatafora, C. Tringali, Anticancer Agents Med. Chem. 2012, 12, 902.
[6] R. Mikstacka, T. Stefanski, J. Rozanski, Cell. Mol. Biol. Lett. 2013, 18, 368.
[7] S. Chandrasekhar, B.V.D. Vijaykumar, B. Mahesh Chandra, Ch. Raji Reddy, P. Naresh, Tet. Lett. 2011, 52, 3865.

Original language	English
Pages	P17
Number of pages	1
Publication status	Published - 5 Dec 2013
Event	17th Sigma-Aldrich Organic Synthesis Meeting - Duinse Polders, Blankenberge, Belgium Duration: 5 Dec 2013 → 6 Dec 2013

Symposium

Symposium	17th Sigma-Aldrich Organic Synthesis Meeting
Country/Territory	Belgium
City	Blankenberge
Period	5/12/13 → 6/12/13

Access to Document

Dolusic poster Blankenberge2013Accepted author manuscript, 2.32 MB

http://www.uclouvain.be/452994.html

4 Poster
1 Abstract

Flow sinteza kombretastatina A-4
Translated title of the contribution: Flow synthesis of Combretastatin A-4Cazin, I., De Backer, L., Collin, S., Desrues, T., Dolusic, E. & Lanners, S., 22 Oct 2016.
Research output: Contribution to conference › Abstract

File
Flow synthesis of combretastatin A-4
Cazin, I., Dolusic, E. & Lanners, S., 5 Nov 2016, p. 53 - HS P 17. 1 p.
Research output: Contribution to conference › Poster

Open Access
File
SELECTIVE SEMIREDUCTION OF ALKYNES AS PART OF AN ENVISAGED CONTINUOUS FLOW SYNTHESIS OF COMBRETASTATIN A-4
Dolušić, E., De Backer, L., Collin, S. & Lanners, S., 13 Jul 2014, p. Book of Abstracts, 14th Belgian Organic Synthesis Symposium, P087, p. 136. 1 p.
Research output: Contribution to conference › Poster › peer-review

Open Access
File

1 Finished

MICROECO: RW-Développement d'un procédé microfluide continu, à empreinte écologique minimale, pour la production de peroxyde d'hydrogène par synthèse directe
Lanners, S. & Dolušić, E.
1/02/13 → 1/02/17
Project: Research

Physical Chemistry and characterization(PC2)
Johan Wouters (Manager) & Carmela Aprile (Manager)
Technological Platform Physical Chemistry and characterization
Facility/equipment: Technological Platform

3 Participation in conference
2 Participation to a Symposium, a study Day

Balticum Organicum Syntheticum 2014
Eduard Dolusic (Poster)
6 Jul 2014 → 9 Jul 2014
Activity: Participating in or organising an event types › Participation in conference
BOSS XIV - 14th Belgian Organic Synthesis Symposium
Eduard Dolusic (Poster)
13 Jul 2014 → 18 Jul 2014
Activity: Participating in or organising an event types › Participation in conference
Microfluidics: Fundamentals and Applications - BePCIS symposium
Eduard Dolusic (Participant)
8 May 2014
Activity: Participating in or organising an event types › Participation to a Symposium, a study Day

Cite this

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title = "Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4",

abstract = "Combretastatin A-4 (1) is a natural product isolated from the South African bushwillow tree Combretum caffrum. It is endowed with a powerful inhibitory activity on microtubule formation as well as a related antiangiogenic activity.[1-2] As such, 1 has a strong potential in the anticancer therapy, prompting the development of new derivatives.[3-6] We have turned our attention to the design of a synthetic procedure for 1 performed entirely in flow, which should enable continuous and rapid production of this useful compound and its derivatives in significant quantities.Presented in this poster is a crucial step in this synthetic strategy - a selective semi-reduction of the triple bond of an alkyne precursor to the Z-double bond in the final product. The Lindlar-type hydrogenation in flow has been described only scarcely and for products typically more stable than Z-stilbenes.[7] We therefore set out to explore this technique and decided to expand it to a wider range of structurally various alkynes.References[1] C. M. Lin, S. B. Singh, P. S. Chu, R. O. Dempcy, J. M. Schmidt, G. R. Pettit, E. Hamel, Mol. Pharmacol. 1988, 34, 200.[2] D. J. Kerr, E. Hamel, M. K. Jung, B. L. Flynn, Bioorg. Med Chem. 2007, 15, 3290.[3] M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin, F. Menichini, Curr. Med. Chem. 2011, 18, 3035.[4] Y. S. Shan, J. Zhang, Z. Liu, M. Wang, Y. Dong, Curr. Med. Chem. 2011,18, 523.[5] C. Spatafora, C. Tringali, Anticancer Agents Med. Chem. 2012, 12, 902.[6] R. Mikstacka, T. Stefanski, J. Rozanski, Cell. Mol. Biol. Lett. 2013, 18, 368.[7] S. Chandrasekhar, B.V.D. Vijaykumar, B. Mahesh Chandra, Ch. Raji Reddy, P. Naresh, Tet. Lett. 2011, 52, 3865.",

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AU - De Backer, Laurent

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AU - Collin, Stéphane

AU - Lanners, Steve

PY - 2013/12/5

Y1 - 2013/12/5

N2 - Combretastatin A-4 (1) is a natural product isolated from the South African bushwillow tree Combretum caffrum. It is endowed with a powerful inhibitory activity on microtubule formation as well as a related antiangiogenic activity.[1-2] As such, 1 has a strong potential in the anticancer therapy, prompting the development of new derivatives.[3-6] We have turned our attention to the design of a synthetic procedure for 1 performed entirely in flow, which should enable continuous and rapid production of this useful compound and its derivatives in significant quantities.Presented in this poster is a crucial step in this synthetic strategy - a selective semi-reduction of the triple bond of an alkyne precursor to the Z-double bond in the final product. The Lindlar-type hydrogenation in flow has been described only scarcely and for products typically more stable than Z-stilbenes.[7] We therefore set out to explore this technique and decided to expand it to a wider range of structurally various alkynes.References[1] C. M. Lin, S. B. Singh, P. S. Chu, R. O. Dempcy, J. M. Schmidt, G. R. Pettit, E. Hamel, Mol. Pharmacol. 1988, 34, 200.[2] D. J. Kerr, E. Hamel, M. K. Jung, B. L. Flynn, Bioorg. Med Chem. 2007, 15, 3290.[3] M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin, F. Menichini, Curr. Med. Chem. 2011, 18, 3035.[4] Y. S. Shan, J. Zhang, Z. Liu, M. Wang, Y. Dong, Curr. Med. Chem. 2011,18, 523.[5] C. Spatafora, C. Tringali, Anticancer Agents Med. Chem. 2012, 12, 902.[6] R. Mikstacka, T. Stefanski, J. Rozanski, Cell. Mol. Biol. Lett. 2013, 18, 368.[7] S. Chandrasekhar, B.V.D. Vijaykumar, B. Mahesh Chandra, Ch. Raji Reddy, P. Naresh, Tet. Lett. 2011, 52, 3865.

AB - Combretastatin A-4 (1) is a natural product isolated from the South African bushwillow tree Combretum caffrum. It is endowed with a powerful inhibitory activity on microtubule formation as well as a related antiangiogenic activity.[1-2] As such, 1 has a strong potential in the anticancer therapy, prompting the development of new derivatives.[3-6] We have turned our attention to the design of a synthetic procedure for 1 performed entirely in flow, which should enable continuous and rapid production of this useful compound and its derivatives in significant quantities.Presented in this poster is a crucial step in this synthetic strategy - a selective semi-reduction of the triple bond of an alkyne precursor to the Z-double bond in the final product. The Lindlar-type hydrogenation in flow has been described only scarcely and for products typically more stable than Z-stilbenes.[7] We therefore set out to explore this technique and decided to expand it to a wider range of structurally various alkynes.References[1] C. M. Lin, S. B. Singh, P. S. Chu, R. O. Dempcy, J. M. Schmidt, G. R. Pettit, E. Hamel, Mol. Pharmacol. 1988, 34, 200.[2] D. J. Kerr, E. Hamel, M. K. Jung, B. L. Flynn, Bioorg. Med Chem. 2007, 15, 3290.[3] M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin, F. Menichini, Curr. Med. Chem. 2011, 18, 3035.[4] Y. S. Shan, J. Zhang, Z. Liu, M. Wang, Y. Dong, Curr. Med. Chem. 2011,18, 523.[5] C. Spatafora, C. Tringali, Anticancer Agents Med. Chem. 2012, 12, 902.[6] R. Mikstacka, T. Stefanski, J. Rozanski, Cell. Mol. Biol. Lett. 2013, 18, 368.[7] S. Chandrasekhar, B.V.D. Vijaykumar, B. Mahesh Chandra, Ch. Raji Reddy, P. Naresh, Tet. Lett. 2011, 52, 3865.

M3 - Poster

SP - P17

Y2 - 5 December 2013 through 6 December 2013

ER -

Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4

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