Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24

Stuart J. Mickel; Gottfried H. Sedelmeier; Daniel Niederer; Friedrich Schuerch; Manuela Seger; Klaus Schreiner; Robert Daeffler; Adnan Osmani; Dominique Bixel; Olivier Loiseleur; Jacques Cercus; Hans Stettler; Karl Schaer; Remo Gamboni; Andrew Bach; Guang-Pei Chen; Weichun Chen; Peng Geng; George T. Lee; Eric Loeser; Joesph McKenna; Frederick R. Kinder Jr; Kurt Konigsberger; Kapa Prasad; Timothy M. Ramsey; Noela Reel; Oljan Repic; Larry Rogers; Wen-Chung Shieh; Run-Ming Wang; Llladar Waykole; Song Xue; Gordon John Florence; Ian Paterson

doi:10.1021/op034133r

Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24

Stuart J. Mickel, Gottfried H. Sedelmeier, Daniel Niederer, Friedrich Schuerch, Manuela Seger, Klaus Schreiner, Robert Daeffler, Adnan Osmani, Dominique Bixel, Olivier Loiseleur, Jacques Cercus, Hans Stettler, Karl Schaer, Remo Gamboni, Andrew Bach, Guang-Pei Chen, Weichun Chen, Peng Geng, George T. Lee, Eric LoeserJoesph McKenna, Frederick R. Kinder Jr, Kurt Konigsberger, Kapa Prasad, Timothy M. Ramsey, Noela Reel, Oljan Repic, Larry Rogers, Wen-Chung Shieh, Run-Ming Wang, Llladar Waykole, Song Xue, Gordon John Florence, Ian Paterson

Research output: Contribution to journal › Article › peer-review

Abstract

Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.

Original language	English
Pages (from-to)	113-121
Number of pages	9
Journal	Organic Process Research & Development
Volume	8
Issue number	1
DOIs	https://doi.org/10.1021/op034133r
Publication status	Published - Jan 2004

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 14 Life Below Water

Keywords

STEREOSELECTIVE SYNTHESIS
KETONES

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10.1021/op034133r

Cite this

Mickel, S. J., Sedelmeier, G. H., Niederer, D., Schuerch, F., Seger, M., Schreiner, K., Daeffler, R., Osmani, A., Bixel, D., Loiseleur, O., Cercus, J., Stettler, H., Schaer, K., Gamboni, R., Bach, A., Chen, G.-P., Chen, W., Geng, P., Lee, G. T., ... Paterson, I. (2004). Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24. Organic Process Research & Development, 8(1), 113-121. https://doi.org/10.1021/op034133r

@article{f7f5e34ca6c14526860c4bb2c681ac7f,

title = "Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24",

abstract = "Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.",

keywords = "STEREOSELECTIVE SYNTHESIS, KETONES",

author = "Mickel, \{Stuart J.\} and Sedelmeier, \{Gottfried H.\} and Daniel Niederer and Friedrich Schuerch and Manuela Seger and Klaus Schreiner and Robert Daeffler and Adnan Osmani and Dominique Bixel and Olivier Loiseleur and Jacques Cercus and Hans Stettler and Karl Schaer and Remo Gamboni and Andrew Bach and Guang-Pei Chen and Weichun Chen and Peng Geng and Lee, \{George T.\} and Eric Loeser and Joesph McKenna and \{Kinder Jr\}, \{Frederick R.\} and Kurt Konigsberger and Kapa Prasad and Ramsey, \{Timothy M.\} and Noela Reel and Oljan Repic and Larry Rogers and Wen-Chung Shieh and Run-Ming Wang and Llladar Waykole and Song Xue and Florence, \{Gordon John\} and Ian Paterson",

year = "2004",

month = jan,

doi = "10.1021/op034133r",

language = "English",

volume = "8",

pages = "113--121",

journal = "Organic Process Research \& Development",

issn = "1520-586X",

publisher = "American Chemical Society (ACS)",

number = "1",

}

Mickel, SJ, Sedelmeier, GH, Niederer, D, Schuerch, F, Seger, M, Schreiner, K, Daeffler, R, Osmani, A, Bixel, D, Loiseleur, O, Cercus, J, Stettler, H, Schaer, K, Gamboni, R, Bach, A, Chen, G-P, Chen, W, Geng, P, Lee, GT, Loeser, E, McKenna, J, Kinder Jr, FR, Konigsberger, K, Prasad, K, Ramsey, TM, Reel, N, Repic, O, Rogers, L, Shieh, W-C, Wang, R-M, Waykole, L, Xue, S, Florence, GJ & Paterson, I 2004, 'Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24', Organic Process Research & Development, vol. 8, no. 1, pp. 113-121. https://doi.org/10.1021/op034133r

TY - JOUR

T1 - Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24

AU - Mickel, Stuart J.

AU - Sedelmeier, Gottfried H.

AU - Niederer, Daniel

AU - Schuerch, Friedrich

AU - Seger, Manuela

AU - Schreiner, Klaus

AU - Daeffler, Robert

AU - Osmani, Adnan

AU - Bixel, Dominique

AU - Loiseleur, Olivier

AU - Cercus, Jacques

AU - Stettler, Hans

AU - Schaer, Karl

AU - Gamboni, Remo

AU - Bach, Andrew

AU - Chen, Guang-Pei

AU - Chen, Weichun

AU - Geng, Peng

AU - Lee, George T.

AU - Loeser, Eric

AU - McKenna, Joesph

AU - Kinder Jr, Frederick R.

AU - Konigsberger, Kurt

AU - Prasad, Kapa

AU - Ramsey, Timothy M.

AU - Reel, Noela

AU - Repic, Oljan

AU - Rogers, Larry

AU - Shieh, Wen-Chung

AU - Wang, Run-Ming

AU - Waykole, Llladar

AU - Xue, Song

AU - Florence, Gordon John

AU - Paterson, Ian

PY - 2004/1

Y1 - 2004/1

N2 - Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.

AB - Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.

KW - STEREOSELECTIVE SYNTHESIS

KW - KETONES

UR - https://www.scopus.com/pages/publications/0842328441

UR - http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/op034133r

U2 - 10.1021/op034133r

DO - 10.1021/op034133r

M3 - Article

SN - 1520-586X

VL - 8

SP - 113

EP - 121

JO - Organic Process Research & Development

JF - Organic Process Research & Development

IS - 1

ER -

Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24

Abstract

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Keywords

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