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Total Synthesis of the Reported Structure of Neaumycin B / Jiaming Ding.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Ding, Jiaming, author.
- Language:
- English
- Subjects (All):
- Chemistry.
- Pharmaceutical sciences.
- Biochemistry.
- Bioengineering.
- Chemistry--Penn dissertations.
- Penn dissertations--Chemistry.
- Local Subjects:
- Chemistry.
- Pharmaceutical sciences.
- Biochemistry.
- Bioengineering.
- Chemistry--Penn dissertations.
- Penn dissertations--Chemistry.
- Physical Description:
- 1 online resource (392 pages)
- Distribution:
- Ann Arbor : ProQuest Dissertations & Theses, 2023
- Contained In:
- Dissertations Abstracts International 85-08B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Language Note:
- English
- Summary:
- Neaumycin B is a macrocyclic polyketide natural product that has shown potent activity against U87 human glioblastoma cell. In this dissertation, the first stereoselective total synthesis of the reported structure of Neaumycin B is reported in a 2.3% overall yield on 90-mg scale. The synthesis features a convergent strategy via union of smaller fragments. Key transformations in the total synthesis involves a gram-scale nickel-catalyzed reductive cross-coupling/spiroketalization to construct the axial/equatorial (A/E) spirocyclic core of Neaumycin B, and a sequential Carreira asymmetric alkynylation/trans-reduction to forge the linear southern hemisphere of the macrocycle.Comparison of the NMR data of synthetic Neaumycin B and that of the natural sample, however, displayed significant deviations. In addition, the reported synthetic Neaumycin B showed no anti-proliferative activity against Glioblastoma cells. The stereo structures that span C3-C6, C8-C14 and C20- C41 of synthetic Neaumycin B were unambiguously confirmed by X-ray crystallography, and C7 stereogenicity was individually verified via Mosher ester analysis. Based on the evidences above, we are confident that synthetic Neaumycin B I prepared as described in this dissertation matches the reported structure, and a future revision on the proposed structure of this natural product will be necessary.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-08, Section: B.
- Advisors: Smith, Amos B., III; Petersson, E. James; Committee members: Winkler, Jeffrey D.; Huryn, Donna; Trauner, Dirk.
- Department: Chemistry.
- Ph.D. University of Pennsylvania 2023.
- Local Notes:
- School code: 0175
- ISBN:
- 9798381510119
- Access Restriction:
- Restricted for use by site license.
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