625856-01-1Relevant academic research and scientific papers
Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2
Smith III, Amos B.,Lin, Qiyan,Doughty, Victoria A.,Zhuang, Linghang,McBriar, Mark D.,Kerns, Jeffrey K.,Boldi, Armen M.,Murase, Noriaki,Moser, William H.,Brook, Christopher S.,Bennett, Clay S.,Nakayama, Kiyoshi,Sobukawa, Masao,Lee Trout, Robert E.
supporting information; scheme or table, p. 6470 - 6488 (2011/02/25)
Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a CaII ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of CaII ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.
Multicomponent Linchpin Couplings. Reaction of Dithiane Anions with Terminal Epoxides, Epichlorohydrin, and Vinyl Epoxides: Efficient, Rapid, and Stereocontrolled Assembly of Advanced Fragments for Complex Molecule Synthesis
Smith III, Amos B.,Pitram, Suresh M.,Boldi, Armen M.,Gaunt, Matthew J.,Sfouggatakis, Chris,Moser, William H.
, p. 14435 - 14445 (2007/10/03)
The development, application, and advantages of a one-flask multicomponent dithiane linchpin coupling protocol, over the more conventional stepwise addition of dithiane anions to electrophiles leading to the rapid, efficient, and stereocontrolled assembly of highly functionalized intermediates for complex molecule synthesis, are described. Competent electrophiles include terminal epoxides, epichlorohydrin, and vinyl epoxides. High chemoselectivity can be achieved with epichlorohydrin and vinyl epoxides. For vinyl epoxides, the steric nature of the dithiane anion is critical; sterically unencumbered dithiane anions afford SN2 adducts, whereas encumbered anions lead primarily to SN2′ adducts. Mechanistic studies demonstrate that the SN2′ process occurs via syn addition to the vinyl epoxide. Integration of the multicomponent tactic with epichlorohydrin and vinyl epoxides permits the higher-order union of four and five components.
Spongistatin synthetic studies. 3. Construction of the C(1-17) spiroketal
Smith III, Amos B.,Lin, Qiyan,Nakayama, Kiyoshi,Boldi, Armen M.,Brook, Christopher S.,McBriar, Mark D.,Moser, William H.,Sobukawa, Masao,Zhuang, Linghang
, p. 8675 - 8678 (2007/10/03)
A convergent synthesis of the C(1-17) AB-ring subunit of the spongistatins, exceedingly scarce and highly antimitotic polyether macrolides, has been achieved via a one-flask dithiane bisalkylation, stereocontrolled spiroketalization, and Julia sulfone coupling/methylenation.
