This PhD thesis was composed of five chapters: a short and highly flexible [3+2+1] synthetic strategy for the synthesis of THP-containing (±)-diospongin A was developed in chapter one, a concise total synthesis of spiroketal-containing aculeatin A in both racemic and enantioselective fashions was described in chapter two, first asymmetric total syntheses of (−)-penicipyrone and (−)-tenuipyrone were accomplished through a biomimetic cascade polycyclization process in chapter three, and synthetic model studies of alotaketal A and ansellone A were completed by syntheses of tricyclic spiroketal core structure and 12,13-dihydroansellone A, respectively, through cascade process in chapter four. After these chapters, a summary of the total work in chapter five and the appendix containing...[ Read more ]

This PhD thesis was composed of five chapters: a short and highly flexible [3+2+1] synthetic strategy for the synthesis of THP-containing (±)-diospongin A was developed in chapter one, a concise total synthesis of spiroketal-containing aculeatin A in both racemic and enantioselective fashions was described in chapter two, first asymmetric total syntheses of (−)-penicipyrone and (−)-tenuipyrone were accomplished through a biomimetic cascade polycyclization process in chapter three, and synthetic model studies of alotaketal A and ansellone A were completed by syntheses of tricyclic spiroketal core structure and 12,13-dihydroansellone A, respectively, through cascade process in chapter four. After these chapters, a summary of the total work in chapter five and the appendix containing NMR spectra and X-ray data were attached.

Chapter one discussed the syntheses of substituted tetrahydropyran-4-ones (THPOs) by developing a short and highly flexible [3+2+1] synthetic strategy, with high diastereoselectivity, featuring 1,3-dipolar cycloaddition of α,β-unsaturated nitrile oxides, SmI₂-promoted chemoselective reductive ring opening of isoxazolines and Amberlyst 15 mediated 6-endo-trig oxa-Michael cyclization. This synthetic strategy was successfully applied in the concise diastereoselective total synthesis of (±)-diospongin A in 8 steps with 20% overall yield from known compound.

Chapter two described a concise total synthesis of aculeatin A as a single spiroisomer featuring (i) phenol oxidative dearomatization and double intramolecular oxa-Michael addition to construct the single spiroisomeric 5,6-spiroketal framework of aculeatins and (ii) chemo-and/ or stereoselective reduction of ketone to install the required secondary alcohol at C4 as the final step.

Chapter three gave the first and concise asymmetric total syntheses of (−)-penicipyrone and (−)-tenuipyrone by developing a biomimetic cascade cyclization strategy, featuring intermolecular Michael addition/cycloketalization (or spiroketalization) process. Later, we studied the cascade Michael addition/cycloketalization (or spiroketalization) reaction of cyclic 1,3-dicarbonyl compounds and α,β-unsaturated carbonyl compounds and found that under acidic conditions the tethered alcohol of the α,β-unsaturated carbonyl compounds plays a critical role in the regioselectivity and reactivity. On the basis of these findings, a detailed mechanism for the cascade Michael addition/cycloketalization (or spiroketalization) reaction was proposed and 43 analogues of penicipyrone and tenuipyrone were prepared in good to excellent yields via this cascade strategy.

Chapter four disclosed a new cascade synthetic strategy and successfully implemented in our model studies of synthesis of tricyclic spiroketal core of alotaketal A and synthesis of 12, 13-dihydroansellone A. The new cascade reaction represented the first example of intramolecular nucleophilic opening of vinyl epoxide with ketonic/acetal oxygen nucleophile. During the course of study, a reliable route for preparation of optically active triene by Bamford-Stevens reaction was developed, and a sequenced allylic chlorination/S_N2(/S_N2′) substitution was utilized to install the allylic hydroxyl group in the late stage. The strategy provided the viability for a collective synthesis of natural products.