Graduation Year

2004

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Bill J. Baker, Ph.D

Committee Member

Robert Potter, Ph.D

Committee Member

Edward Turos, Ph.D

Committee Member

Abdul Malik, Ph.D

Keywords

marine natural products, tryptophan catabolism, chemical defense, Antarctic invertebrates, erebusinone

Abstract

This thesis describes the chemical investigation of three marine sponges from Antarctica and the total syntheses of natural products erebusinone (12) and its derivative, erebusinonamine (52). Investigation of the yellow Antarctic marine sponge Isodictya setifera resulted in the isolation of two secondary metabolites, purine analog (32) and 3-hydroxykynurenine (24). Chemical investigation of Isodictya setifera led to the isolation of six secondary metabolites which included 5-methyl-2-deoxycytidine (25), uridine (28), 2-deoxycytidine (31), homarine (37), hydroxyquinoline (33), 3-hydroxykynurenine (24). The latter two compounds were found to be intermediates of tryptophan catabolism in crustaceans. From the Antarctic marine sponge Isodictya antractica ceramide analog (39) was isolated and its chemical structure was assigned by a combination of spectroscopic and chemical analyses. Stereochemistry was determined by modified Mosher's method. Erebusinone (12), a yellow pigment isolated from the Antarctic marine sponge Isodictya erinacea has been implicated in molt inhibition and mortality against the Antarctic crustacean amphipod, Orchomene plebs, possibly serving as a precursor of a xanthurenic acid analog.

Thought to act as a 3-hydroxykynurenine 24 mimic, erebusinone (12) may be involved chemical defense. This appears to be the first example in the marine realm of an organism utilizing tryptophan catabolism to modulate molting as a defensive mechanism. To further investigate the bioactivity and ecological role of erebusinone (12), the synthesis of this pigment was carried out in an overall yield of 44% involving seven steps which were economical and convenient. Erebusinonamine (52) was also similarly synthesized in eight steps with an overall yield of 45%.

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