Synthesis of the LMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the principal causative toxin for ciguatera fish poisoning around the Caribbean Sea areas, is described. The key feature of the synthesis is the stereoselective introduction of an angular methyl group on the sterically encumbered seven-membered M-ring by the application of a hydrogen atom transfer-based reductive olefin coupling.
The photoactivatable chemically induced dimerization (photo-CID) technique for tag-fused proteins is one of the most promising methods for regulating subcellular protein translocations and protein-protein interactions.H owever, light-induced covalent protein dimerization in living cells has yet to be established, despite its various advantages.Herein, we developed ap hotoactivatable covalent protein-labeling technology by applying ac aged ligand to the BL-tag system, ac ovalent protein labeling system that uses mutant b-lactamase.Wefurther developed CBHD,acaged protein dimerizer, using caged BL-tag and HaloTag ligands,a nd achieved lightinduced protein translocation from the cytoplasm to subcellular regions.I na ddition, this covalent photo-CID system enabled quickp rotein translocation to al aser-illuminated microregion. These results indicate that the covalent photo-CID system will expand the scope of CID applications in the optical manipulation of cellular functions.
Synthesis of the JKLMN-ring fragment
of Caribbean ciguatoxin C-CTX-1,
the causative toxin of ciguatera fish poisoning in the Caribbean Sea
and the Northeast Atlantic areas, is described in detail. Key to the
synthesis are a [2,3]-sigmatropic rearrangement to construct a seven-membered
α-hydroxy exo-enol ether, stereoselective construction
of an angular tetrasubstituted stereogenic center on the seven-membered
M-ring by a hydrogen atom transfer-based reductive olefin coupling,
Suzuki–Miyaura coupling of the KLMN-ring enol phosphate with
a highly congested M-ring, and silica gel-mediated epoxide ring opening
to form the J-ring. Comparison of the nuclear magnetic resonance spectroscopic
data for the synthesized fragment with those for the natural product
provided support for the formerly assigned structure of the N-ring
in the right-hand terminal of C-CTX-1.
The photoactivatable chemically induced dimerization (photo-CID) technique for tag-fused proteins is one of the most promising methods for regulating subcellular protein translocations and protein-protein interactions.H owever, light-induced covalent protein dimerization in living cells has yet to be established, despite its various advantages.Herein, we developed ap hotoactivatable covalent protein-labeling technology by applying ac aged ligand to the BL-tag system, ac ovalent protein labeling system that uses mutant b-lactamase.Wefurther developed CBHD,acaged protein dimerizer, using caged BL-tag and HaloTag ligands,a nd achieved lightinduced protein translocation from the cytoplasm to subcellular regions.I na ddition, this covalent photo-CID system enabled quickp rotein translocation to al aser-illuminated microregion. These results indicate that the covalent photo-CID system will expand the scope of CID applications in the optical manipulation of cellular functions.
The convergent synthesis of the HIJKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the major causative toxin for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is disclosed. The synthesis features a late-stage iron-catalyzed hydrogen atom transfer-initiated reductive olefin coupling to install the N-ring and a Suzuki–Miyaura coupling/thioacetalization strategy for the convergent assembly of the hexacyclic HIJKLM-ring skeleton.
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