Evolution of a gram-scale synthesis of (+)-discodermolide

Amos B. Smith; Thomas J. Beauchamp; Matthew J. Lamarche; Michael D. Kaufman; Yuping Qiu; Hirokazu Arimoto; David R. Jones; Kaoru Kobayashi

doi:10.1021/ja0015287

Evolution of a gram-scale synthesis of (+)-discodermolide

Amos B. Smith, Thomas J. Beauchamp, Matthew J. Lamarche, Michael D. Kaufman, Yuping Qiu, Hirokazu Arimoto, David R. Jones, Kaoru Kobayashi

LIF - Molecular and Chemical Life Science

University of Pennsylvania

Research output: Contribution to journal › Review article › peer-review

255 Citations (Scopus)

Abstract

An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphoniun salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.

Original language	English
Pages (from-to)	8654-8664
Number of pages	11
Journal	Journal of the American Chemical Society
Volume	122
Issue number	36
DOIs	https://doi.org/10.1021/ja0015287
Publication status	Published - 2000 Sept 13

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abstract = "An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphoniun salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.",

author = "Smith, {Amos B.} and Beauchamp, {Thomas J.} and Lamarche, {Matthew J.} and Kaufman, {Michael D.} and Yuping Qiu and Hirokazu Arimoto and Jones, {David R.} and Kaoru Kobayashi",

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AU - Smith, Amos B.

AU - Beauchamp, Thomas J.

AU - Lamarche, Matthew J.

AU - Kaufman, Michael D.

AU - Qiu, Yuping

AU - Arimoto, Hirokazu

AU - Jones, David R.

AU - Kobayashi, Kaoru

PY - 2000/9/13

Y1 - 2000/9/13

N2 - An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphoniun salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.

AB - An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphoniun salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.

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Evolution of a gram-scale synthesis of (+)-discodermolide

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