title: Approaches to the synthesis of some tyrosine-derived marine sponge metabolites: synthesis of verongamine and purealidin N.
abstract: The oxidation of tyrosine ethyl ester (7) with Na(2)WO(4)/H(2)O(2) in ethanol, dimethyldioxirane in acetone, or methyltrioxorhenium/H(2)O(2) in EtOH gave the corresponding tyrosine oxime (8) in high yield. Controlled bromination of the aromatic ring gave the monobromo oxime (9), the dibromo oxime (10), or the spiroisoxazoline (11) depending upon reaction conditions. Synthesis of the known metabolite verongamine (15) was achieved by oxidation of O-methyl bromotyrosine methyl ester and amidation of the resulting oxime ester (14) with histamine. The mono- and di-bromotyrosine oxime derivatives (9 and 10) were further transformed into the naturally occurring nitriles (16 and 17) by base hydrolysis of the ester and acid-catalyzed decarboxylation. Wadsworth-Emmons olefination of the dibromobenzaldehyde (20b) with phosphonate (18) gave the pyruvate silylenolether (21b). Deprotection and in situ oxime formation gave the oxime ester (23b). Attempted purification of the pyruvate ester resulted in a homoaldol condensation yielding butenolide (22). Amidation of the oxime ester (23b) with histamine, followed by deprotection of the MOM ether gave the first synthesis of purealidin N (28). Oxidative spirocyclization of the phenolic oxime ester (23d) with a polymer-bound iodosyl diacetate gave the spiroisoxazoline (24) and represents a formal synthesis of aerothionin (26a), homoaerothionin (26b), and aerophobin-1 (25).
authors.affiliation: Department of Chemistry, University of Missouri-St. Louis, 8001 Natural Bridge Road, St. Louis, Missouri 63121-4499, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Boehlow
authors.forename: J J
authors.initials: JJ
authors.lastname: Harburn
authors.forename: C D
authors.initials: CD
authors.lastname: Spilling
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001969:Bromobenzenes / Q000138:chemical synthesis*; D006633:Histamine Antagonists / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D009574:Nitro Compounds / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D011161:Porifera / Q000737:chemistry*; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001969:Bromobenzenes; D006633:Histamine Antagonists; D009574:Nitro Compounds; D010091:Oximes; D018100:Receptors, Histamine H3; C429963:purealidin N; C086787:verongamine; D014443:Tyrosine