Enantioselective Total Synthesis of (+)-Amphirionin-4

Arun K. Ghosh, Prasanth R. Nyalapatla
2016 Organic Letters  
An enantioselective total synthesis of (+)-amphirionin-4 has been accomplished in a convergent manner. The synthesis features an efficient enzymatic lipase resolution to access the tetrahydrofuranol core in optically-active form. The functionalized tetrahydrofuran derivative was synthesized via an oxocarbenium ion-mediated highly diastereoselective syn-allylation reaction. The polyene side chain was synthesized using Stille coupling reactions. Nozaki-Hiyama-Kishi coupling was utilized to
more » ... ct the C-8 stereocenter and complete the synthesis of (+)amphirionin-4. Graphical Abstract Marine dinoflagellates of the genus Amphidiuium species are rich sources of bioactive polyketide-like natural products with intriguing biological properties. 1,2 Recently, Tsuda and co-workers isolated a number of polyketides, amphirionins-2, -4 and -5 from the dinoflagellate Amphidiuium species. 3,4,5 Among these, the linear polyke-tide (+)amphirionin-4 (1, Figure 1 ) was isolated from the Amphidiuium KCA09051 strain in the benthic sea sand collected off the Iriomote Island. This compound exhibited exceptionally potent proliferation-promoting activity (95% promotion) on murine bone marrow stomal ST-2 cells at 0.1 ng/mL concentration. Interestingly, it did not show proliferation promotion when administered to
doi:10.1021/acs.orglett.6b00942 pmid:27116318 pmcid:PMC5328589 fatcat:wjzv5srihvf45o7hgzihnj5nq4