This PhD thesis was composed of four chapters: chapter one describes total synthesis of purported cephalosporolides H and I, penisporolide B, and their Stereoisomers, chapter two presents asymmetric total syntheses of ent-ascospiroketal A/B, chapter three is focus on the development of novel synthetic route for 6-alkyl-3-hydroxy-2-pyrone and its application in collective total syntheses of the penostatin family. After these chapters, a summary of the whole work in chapter four and the appendix containing NMR spectra was attached.

Chapter one discussed the development of a unified, bioinspired synthetic strategy to access four possible diastereomers of unique 2,2-dimethyl-[5,5]-spiroacetal-cis-fused-γ-lactone (Me₂SAFL), featuring pyridinium chlorochromate (PCC)-promoted oxidative ring...[ Read more ]

This PhD thesis was composed of four chapters: chapter one describes total synthesis of purported cephalosporolides H and I, penisporolide B, and their Stereoisomers, chapter two presents asymmetric total syntheses of ent-ascospiroketal A/B, chapter three is focus on the development of novel synthetic route for 6-alkyl-3-hydroxy-2-pyrone and its application in collective total syntheses of the penostatin family. After these chapters, a summary of the whole work in chapter four and the appendix containing NMR spectra was attached.

Chapter one discussed the development of a unified, bioinspired synthetic strategy to access four possible diastereomers of unique 2,2-dimethyl-[5,5]-spiroacetal-cis-fused-γ-lactone (Me₂SAFL), featuring pyridinium chlorochromate (PCC)-promoted oxidative ring expansion of β-hydroxy cyclic ethers and dehydrative ring-contraction rearrangement of 10-membered lactones. Synthetic utility of this strategy was demonstrated by total syntheses of 12 Me₂SAFLs, corresponding to the purported cephalosporolide H (CesH), cephalosporolide I (CesI), and penisporolide B (PenB) and their possible diastereomers. Comprehensive NMR data analysis suggested that the tricyclic Me₂SAFL core of CesH, CesI, and PenB should be revised to the same relative (3R*,4R*,6S*,9R*) configuration and that the side chains required an unknown constitutional structure revision.

Chapter two described a novel synthetic strategy for the asymmetric total synthesis of ent-ascospiroketals A and B, which is guided by a new hypothetic biosynthesis of the tricyclic spiroketal core of ascospiroketals A and B. The synthesis features an efficient ring contraction rearrangement of the 10-membered lactone to the tricyclic spiroketal cis-fused-γ-lactone core, which served as the common intermediate for the synthesis of both ent-ascospiroketals A and B through the Stille coupling reaction at the final step. In addition, seven diastereomers were prepared to conclusively confirm the structure of ent-ascospiroketal B.

Chapter three gave the development of new synthetic route for 6-alkyl-3-hydroxy-2-pyrone and progress on the collective total syntheses of the penostatin family. The concise and efficient synthetic route to access the mutisubstituted 3-hydroxy-2-pyrone was applied in convergent asymmetric total syntheses of penostatin A, ent-penostatin B, penostatin C, ent-penostatin D. Also, synthetic studies towards more complex penostatin G was attempted, which indicated that the tricyclic IMDA adducts with naked bridged alcohol were easily decomposed due to retro aldol reaction or decarboxylation pathway. The collective total synthesis was enabled by intramolecular pyrone Diels Alder reaction and subsequent decarboxylation to the structurally unique bicyclo[4.3.0]nonane framework, Lewis acid mediated alkenylation, selenoxide elimination, and PCC oxidative transformation at the final stage of the synthesis.