Abstract
R. Joseph. Synthesis of Unusual Sterols from Marine Sources, 388 pages, 12 tables, 38 figures, 2017.
The syntheses of some unusual marine sterols are reported. 24-Epiconicasterol, an epimer of the bioactive marine sponge sterol conicasterol, an epimer of the bioactive marine sponge sterol conicasterol was synthesized in 10 steps and a 13% overall yield from ergosterol. Similarly, the 24-epimer of the bioactive sponge sterol theonellasterol, 24-epitheonellasterol, was synthesized from stigmasterol. Pfiesterol, an unusual sterol isolated from the toxic dinoflagellate Pfiesteria piscicida and potential biomarker for the species, was synthesized from 16-dehydropregnolone acetate. 4-Methylcholestane-3β,4β-diol, a synthetic pavlovol, was synthesized from cholestenone in a seven-step sequence and a 38% overall yield. The simple analogs of petrosterol, a bioactive sponge sterol and potential inhibitor of invertebrate sterol metabolism, were synthesized as a mixture from the i-methyl 22-iodide in a six-step sequence and a 43% overall yield. The structures of two novel highly alkylated cyclopropyl sterols from a tropical jewel orchid were elucidated by synthesis.
Methods for sterol synthesis were developed. The use of a sealed reaction vessel shortened the reaction time for the Kirk-Petrow reaction by at least a day. 1-Dodecanethiol was successfully used instead of thiophenol to obtain an odorless product in good yield and with equivalent reactivity. A new method for the oxidation of allylic alcohols via thiyl radicals was developed. Phenyl disulfide and visible light were used to generate the thiyl radicals. This is the first account of the direct involvement of thiyl radicals in the oxidation of allylic alcohols.
This work provided synthetic methods for the aforementioned unusual marine sterols and analogs, which can be used as reference compounds and samples for biological studies. The consumption of unusual marine sterols may affect the growth and development ecologically important marine grazers like copepods.
Keywords: Sterols, marine sterols, biomarkers, unusual sterols, marine sponges, harmful algae, dinoflagellates, phytosterols, pavlovols, conicasterol, organic, synthesis, bioactive sterols, sterol metabolism, thiyl radicals, allylic alcohols, selective oxidation.
R. Joseph
Candidate for the degree of Doctor of Philosophy, December 2017
José-Luis Giner, Ph.D.
Department of Chemistry
State University of New York College of Environmental Science and Forestry,
Syracuse, New York