Date of Graduation

12-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Matthias C. McIntosh

Committee Member

Neil T. Allison

Second Committee Member

Nan Zheng

Third Committee Member

Ryan Tian

Keywords

Organic Synthesis, Natural Products

Abstract

The dissertation describes asymmetric synthesis towards C29-C34 moiety of fragment A of the Antascomicin B and Thermal azole based Claisen rearrangements. In chapter 1, we describes asymmetric synthesis towards C29-C34 moiety of fragment A of the Antascomicin B. The non-immunosuppressant Rapamycin, Ascomycin, and Tacrolimus (FK506), strongly binds with FKBP12, the ligand FKBP12 complexes responsible for immunosuppressive activity. Antascomicin B structurally related to Rapamycin, Ascomycin, and Tacrolimus (FK506), binds strongly to FKBP12, yet does not shown immunosuppressive activity. The ligand FKBP12 binding complexes shown to have potent neuroprotective and neurogenerative properties in mouse models of Parkinson’s disease. The linear synthesis of C29-C34 moiety of fragment A of the Antascomicin B was highlighted through chemical reactions include an Delis Alder reaction, asymmetric transfer hydrogenation (ATH), epoxide ring opening reactions. In chapter 2, we describes novel methodologies of preparing 2-butenyl benzothiazole derivatives using aza-Claisen rearrangement, through N, S-ketene acetals intermediates. The precursor N-allyl-N, S-ketene acetals were prepared in situ from the reaction of N-allyl benzothiazolium salts. N-allyl benzothiazolium salts synthesized by simply alkylated 2-methyl benzothiazole with various allyl bromide derivatives. Despite of the traditional approaches, our proposed synthetic methodology of N, S-ketene acetals that requires only weak base, possesses broad functional group compatibility, and require no cryogenic conditions.

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