Novel single electron transfer (SET) induced photochemical processes are being developed and applied as part of unique and efficient strategies for natural product synthesis. In one area, a novel sequence for construction of harringtonine alkaloid pentacyclic skeleton based upon SET- photocyclization reactions of silyallyl iminium salts has been developed and is being used in investigations focusing on the synthesis of the representative harringtonines, cephalotaxine and its 11-hydroxy analog. In another effort, newly discovered SET-photocyclizations of unsaturated alpha-silyamino ketones and esters is being subjected to detailed study and the synthetic potential of these processes is being probed by their employment in routes to important members of the indolizidine, quinolizidine and pyrrolizidine alkaloid families. In this context, stereocontrolled syntheses of the biologically interesting indolizidines, 6-epicastanospermine and tylophorine, which utilize photocyclizations of 2- acryloyl-1-silylmethyl pyrrolidines have been designed. SET-induced photocyclizations of related silylmethylpiperidines serve as the basis for proposed routes targeted at the simple quinolizidine alkaloid, lupinine, and the structurally and biologically more interesting member of this family, sparteine. Retronecanol and retronecine serve as representative targets for studies designed to demonstrate the general synthetic utility of SET-photocyclizations of alpha-silylmethylpyrrolidin-2-yl acrylates in the area of pyrrolizidine alkaloid synthesis. These studies will be extended to test the viability of photo-SET reactions occurring between alpha-silylbenzyl amines an conjugated enones with the aim of developing a new N-heteroannulation methodology. The synthetic potential of these processes will be demonstrated by their employment inlycorane and crinane alkaloid synthetic strategies. In another area, studies have been designed to test proposals which have been offered to explain the stereochemistry od diradical cyclization processes as part of efforts focusing on the development of stereoselective methods for 8- and 13-methylprotoberberine synthesis. In a final area, the scope of the newly uncovered photo-Pictet Spengler cyclization reaction of N-arylalkyliminium salts will be investigated. This new process will be used to prepare a number of 1,1- spirocyclic hydroisoindoles and hydroisoquinolines as part of a collaborative effort with researches at NIH. Studies will also be conducted to determine if the conceptual basis of this reaction can be applied to the development of the new SET-photocyclization reactions in arene-enone systems.
