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

Résultats de recherche: Contribution à un événement scientifique (non publié)Poster

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Résumé

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.
langue originaleAnglais
PagesP17
Nombre de pages1
étatPublié - 5 déc. 2013
Evénement17th Sigma-Aldrich Organic Synthesis Meeting - Duinse Polders, Blankenberge, Belgique
Durée: 5 déc. 20136 déc. 2013

Colloque

Colloque17th Sigma-Aldrich Organic Synthesis Meeting
PaysBelgique
La villeBlankenberge
période5/12/136/12/13

Empreinte digitale

alkynes
Combretum caffrum
chemical derivatives
synthesis
stilbenes
hydrogenation
antineoplastic agents
microtubules
therapeutics
cells
methodology

Citer ceci

De Backer, L., Dolušić, E., Collin, S., & Lanners, S. (2013). Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4. P17. Poster présenté � 17th Sigma-Aldrich Organic Synthesis Meeting, Blankenberge, Belgique.
De Backer, Laurent ; Dolušić, Eduard ; Collin, Stéphane ; Lanners, Steve. / Partial alkyne reduction in flow : Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4. Poster présenté � 17th Sigma-Aldrich Organic Synthesis Meeting, Blankenberge, Belgique.1 p.
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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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De Backer, L, Dolušić, E, Collin, S & Lanners, S 2013, 'Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4', 17th Sigma-Aldrich Organic Synthesis Meeting, Blankenberge, Belgique, 5/12/13 - 6/12/13 p. P17.

Partial alkyne reduction in flow : Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4. / De Backer, Laurent; Dolušić, Eduard; Collin, Stéphane; Lanners, Steve.

2013. P17 Poster présenté � 17th Sigma-Aldrich Organic Synthesis Meeting, Blankenberge, Belgique.

Résultats de recherche: Contribution à un événement scientifique (non publié)Poster

TY - CONF

T1 - Partial alkyne reduction in flow

T2 - Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4

AU - De Backer, Laurent

AU - Dolušić, Eduard

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

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De Backer L, Dolušić E, Collin S, Lanners S. Partial alkyne reduction in flow: Adaptation of the lindlar protocol as part of a flow synthesis of combretastatin A-4. 2013. Poster présenté � 17th Sigma-Aldrich Organic Synthesis Meeting, Blankenberge, Belgique.