ABSTRACT
An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (-)-pericosine C.
Subject(s)
Carbasugars/chemical synthesis , Epoxy Compounds/chemical synthesis , Molybdenum/chemistry , Phosphoric Acids/chemistry , Shikimic Acid/analogs & derivatives , Carbasugars/chemistry , Catalysis , Epoxy Compounds/chemistry , Molecular Structure , Shikimic Acid/chemical synthesis , Shikimic Acid/chemistry , StereoisomerismABSTRACT
The stereoselective synthesis of (-)-pericosine B, which is the antipode of the cytotoxic metabolite of the fungus Periconia byssoides OUPS-N133 separated from the sea hare, was accomplished in 9 steps in 12% total yield from (-)-quinic acid, together with the synthesis of its epimer. Every crucial step of this total synthesis, including ring opening of a beta-epoxide and NaBH4 reduction of an unstable beta,gamma-unsaturated enone, proceeded with excellent stereoselectivity.
Subject(s)
Shikimic Acid/analogs & derivatives , Biological Products/chemical synthesis , Biological Products/toxicity , Cell Line, Tumor , Humans , Shikimic Acid/chemical synthesis , Shikimic Acid/toxicity , StereoisomerismABSTRACT
We have demonstrated the synthesis of regioisomerically pure unsymmetrical xanthene derivatives consisting of three units which can be independently modified to control their physical properties. The photochemical properties of the synthetic unsymmetrical xanthene derivatives were investigated in solution by UV-vis absorption and fluorescence measurements, and their cell imaging properties were examined by confocal laser-scanning microscopy.
Subject(s)
Benzophenones/chemical synthesis , Coloring Agents/chemical synthesis , Fluorescent Dyes/chemical synthesis , Photochemistry/methods , Xanthenes/chemical synthesis , Benzophenones/chemistry , Cells/drug effects , Coloring Agents/chemistry , Fluorescent Dyes/chemistry , Humans , Microscopy, Confocal , Models, Molecular , Molecular Structure , Spectrometry, Fluorescence , Stereoisomerism , Tumor Cells, Cultured , Xanthenes/chemistryABSTRACT
Pericosines are unique C(7) cyclohexenoid metabolites of Periconia byssoides OUPS-N133 fungus that was originally isolated from the sea hare, Aplysia kurodai. Pericosines show significant in vitro cytotoxicity against P388 lymphocytic leukemia cells. Pericosine A, in particular, shows the most potent activity and significant in vivo antitumor activity against P388 cells. Thus, pericosines are promising candidates for seed compounds of anticancer drugs. However, before the total syntheses of pericosines were accomplished, their stereo structures could not be determined by spectral analyses because they have multi-functionalized cyclohexenoid structures with torsional strain. In this review, synthetic efforts for pericosines in this decade are surveyed.
ABSTRACT
The first total synthesis of (+)- and (-)-pericosine A has been achieved, enabling the revision and determination of the absolute configuration of this antitumor natural product as methyl (3S,4S,5S,6S)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate. Every step of this total synthesis proceeded well with excellent stereoselectivity. Structures of the intermediates in crucial steps were confirmed by detailed 2D NMR analysis.
