title: Studies toward the total synthesis of mumbaistatin, a highly potent glucose-6-phosphate translocase inhibitor. Synthesis of a mumbaistatin analogue.
abstract: A strategy for the total synthesis of the highly potent glucose-6-phosphate translocase inhibitor mumbaistatin (1) and structural analogues was elaborated. Such compounds represent a lead structure in the development of potential new drugs for the treatment of diabetes. To evaluate the general strategy, the close mumbaistatin analogue 10 was synthesized in a convergent manner. The anthraquinone building block 20 was efficiently prepared via aryne/phthalide annulation. After conversion of 20 into the corresponding 9,10-dimethoxyanthracene-1-carbaldehyde derivative (13), coupling with a lithiated arene (12) and subsequent multiple oxidation under Jones conditions yielded the mumbaistatin analogue 10. The preparation of the functionalized arene intermediates was achieved exploiting highly regioselective bromination and ortho-lithiation reactions.
authors.affiliation: Institut für Organische Chemie, Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kaiser
authors.forename: Lothar
authors.initials: L
authors.lastname: Schwink
authors.forename: Janna
authors.initials: J
authors.lastname: Velder
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Schmalz
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017920:Antiporters; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008745:Methylation; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D017920:Antiporters; D004791:Enzyme Inhibitors; D009004:Monosaccharide Transport Proteins; C111261:glucose 6-phosphate(transporter); C430985:mumbaistatin; D010770:Phosphotransferases