Part I. 2-pyridone [4+4] photocycloaddition and its application towards the total synthesis of fusicoccin A. Part II. The first total synthesis of (minus)-SNF4435 C and (+)-SNF4435 D

Part I of this thesis centers on the intermolecular and intermolecular [4+4]-photocycloadditon of 2-pyridones, an attractive substrate for [4+4]-photocycloaddition, since the aromatic stabilization of amide group of 2-pyridone, due to the delocalization of electrons over the ring system, dramatically influences the dime character.; Chapter 1 in the Part I demonstrates a novel methodology for the construction of polyquinane architecture by way of a transannular ionic cyclization of a cyclooctadiene, which is generated from intermolecular [4+4]-photocycloaddition of 2-pyridones. [4+4]-photocycloaddition of 2-pyridones yields a rigid polycyclic product containing a 1,5-cyclooctadiene. The cis isomer, with the alkenes in close proximity, undergoes a transannular reaction when treated with chlorine to give a polyquinane product. This two-step sequence generates complex polyquinanes with up to eight new stereogenic centers from achiral aromatic pyridones. This useful synthetic methodology for the transannular ring closure can be applied to natural product synthesis containing polyquinanes skeleta.; Chapter 2 in the Part I concentrates on the synthetic study toward the total synthesis of Fusicoccin A by intermolecular [4+4]-photocycloaddition of tethered bis-2-pyridones as a key step. Fusicoccin A remains a conspicuous synthetic challenge with its combination of complex architecture, interesting biological activity, and the difficulties of cyclooctane construction. We have focused on the fusicoccin ring system, due to how its skeletons relate to our [4+4]-photoadduct (5-8-5 ring system), and envisioned the intermolecular [4+4]-photocycloaddition of tethered bis-2-pyridones to achieve total synthesis of fusicoccin ring backbone. Following completion of an advanced model system, the synthetic studies towards an enantioselective total synthesis are described.; Part II, Chapter 3 of this thesis demonstrates the first total synthesis of (-)-SNF4435 C and (+)-SNF4435 D by a convergent and highly stereoselective one-pot Stille coupling/double electrocylization. (-)-SNF4435 C and (+)-SNF4435 D are structurally novel and unique natural products that exhibit immunosuppressant and MDR reversal activities. We envisaged that a tetraene, which is generated via Stille coulpling, is able to undergo a thermal 8pi conrotatory electrocyclization to generate the cyclooctatriene, which can then undergo a further thermal 6pi electron disrotatory electrocyclization to generate the desired bicyclic [4.2.0] core. From our model studies, we established that the size and positioning of substituents on a tetraene, along with the Woodward Hoffmann rules, control the relative stereochemistry at the four adjacent chiral centers that are generated in the 8pi, 6pi electrocyclization cascade, which means the ratio of endo and exo products was controlled by the choice of the RZ substituent at C-1 on a tetraene. (Abstract shortened by UMI.)...