Comparison of Select Unsaturated Lactams and their Sultam Counterparts to Photoactivation. Efforts Towards the Total Synthesis of Salicifoline and Pseudolarolide E

by Dura, Robert Douglas

Abstract (Summary)
The first project addressed in this dissertation involved the synthesis of highly strained, bridged sultams and lactams. With a primary focus on the sultams, triplet-sensitized irradiation in acetone solution gave rise exclusively to a tetracyclic sultam through a regiospecific di-pi-methane rearrangement. A strong preference for benzo-vinyl bridging distal to the sulfonamide functional group was observed. This transformation constituted a facile means for accomplishing the ring contraction of a bridgehead sultam. In a continuing exploration of the photoactivation of sultam and lactam systems, a convergent strategy was developed to access bridgehead sultams and carboxamides of varying sizes bearing a diene unit. The key reactions in these syntheses were the use of a Grubbs I mediated ring-closing metathesis, an intramolecular Heck reaction providing the desired tricyclic intermediates, and a twofold dehydrobromination mediated by tetrabutylammonium fluoride in DMSO. Irradiation of the azatricyclosultam led principally via SO2-N bond homolysis and [1,5] sigmatropic rearrangement to 5,6-dihydro-4bH-10-thia-6-azabenzo[a]azulene 10,10-Dioxide. The methano-bridged carboxamide proceeded via disrotatory cyclization to the exo cyclobutenamide, and the ethano-bridged carboxamide resisted photoisomerization. Based on the prior set of results, a non-bridged planar arrangement was postulated to elicit similar chemical transformations in structurally related systems. A parallel strategy allowed access to a pair of pyridoisoindolones and their previously unknown sultam counterparts. Detailed study of the excited-state chemistry of 4H-pyrido[2,1-a]isoindol-6-one and 10b-methyl-10bH-pyrido[2,1-a]isoindol-6-one showed both lactams to be subject to [4+2] dimerization under acetone-sensitized conditions. No dimers could be isolated from the sultam photolysates under any conditions. While the 4b-methylazafluorene 9,9-Dioxide underwent extensive polymerization, 8H-azafluorene 9,9-dioxide was transformed via direct irradiation at 350 nm into a thienopyridine and benzoisothiazole via [1,3]-sigmatropy involving the S-N bond and heterocyclic ring cleavage, respectively. Next to be addressed was the total synthesis of salicifoline. Salicifoline was isolated from Euphorbia salicifolia in Budapest, Hungary during 2001, and represents the first example of a cembranoid derived tricyclic jatrophene diterpene polyester containing a novel bicyclo[5.5.1]core. Aside from the evident synthetic challenge, there is a pronounced interest in cembranoid jatrophenes due to their inherent multi-drug resistance reversing properties. The final project deals with the total synthesis of pseudolarolide E. This triterpene dilactone was isolated from Pseudolarix kaempferi and is commonly used in traditional Chinese medicine to treat a variety of skin conditions. This structure holds synthetic interest due to the rare 11-membered core it possesses.
Bibliographical Information:


School:The Ohio State University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:sultams lactams salicifoline psuedolarolide e photochemistry di pi methane


Date of Publication:01/01/2008

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