I. THE TOTAL SYNTHESIS OF (+,-)-CHELIDONINE. II. STUDIES DIRECTED TOWARD THE SYNTHESIS OF STREPTONIGRIN

MARY P KOLECK, Purdue University

Abstract

Part I. A review of the prior syntheses of the benzophenanthridine alkaloid ((+OR-))-chelidonine (1), and a summary of its biological activity and biosynthesis are presented. The key step in this total synthesis of ((+OR-))-chelidonine is the condensation of the Schiff base 39 with 3,4-(methylenedioxy)homophthalic anhydride 44. A variety of reaction conditions were explored to maximize the formation of the desired thermodynamically less stable cis diastereomer 53. Conversion of 53 to its acid chloride was achieved without the concomitant formation of the indeno{1,2-c}isoquinolone 59. The migration of an aromatic ring observed upon treatment of the diazo ketone 55 with acid is similar to the Hayashi rearrangement. Part II. A review of the past synthetic approaches to the antitumor antibiotic, streptonigrin (64) and a summary of its biological activity and mechanism of action are presented. A novel approach to the ring system present in steptonigrin (64) is described. The AB ring system is made by a modification of the Friedlander quinoline synthesis. The convergent step is the formation of the pyridine ring C. The strategy for this reaction is based on the known conversion of flavones to pyridines under similar conditions. Although this route has not been successful for the preparation of streptonigrin, it appears attractive for the preparation of structural analogs. Structural analogs, which display a more favorable therapeutic index and do not exhibit the suppression of hematopoietic tissue caused by streptonigrin (64), are of interest. A portion of this route has been explored in these laboratories in a model compound study and has been shown to be successful.

Degree

Ph.D.

Subject Area

Organic chemistry

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