Total Synthesis of Natural Products: (−)-Kaitocephalin, Monensin B and Laidlomycin

조회수 : 271 등록일 : 2020.09.24 13:33

일시 : 2020.09.23 17:00
소속 : 강원대
발표자 : 이원철
장소 : R 1314/ ZOOM

Kaitocephalin, which is a naturally occurring glutamate receptor antagonist, was isolated from the filamentous fungus Eupenicillium shearii PF1191 by Seto and Shin-ya et al. in 1997.1 Its novel structure is composed of tripeptide as alanine, proline and serine. Kaitocephalin showed noteworthy antagonism against ionotropic glutamate receptors (iGluRs), including NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/KA (kainic acid) receptors, which would function as a potential therapeutic neuroprotective agents for the treatment of Alzheimer’s disease, Parkinson’s disease and epilepsy. The key steps involved the enantioselective desymmetrization of the N-Cbz-protected seriol to install the C4 quaternary chiral center and the intramolecular mercury(II)-mediated N-cyclization of (Z)-alkene followed by reductive demercuration to construct the pyrrolidine ring.

Monensin B and Laidlomycin, which are a polycyclic polyether ionophoric antibiotics, were prepared from a Streptomyces cinnamonensis ATCC 15413 and sp. CS684, respectively.2 These polyketides showed various physiological properties such as antimycoplasmal, antimicrobial and anti-HIV activities, reversal effect on colchicine resistance in human carcinoma, growth promoter for ruminants, and anticoccidial activity for poultry. Toward the synthesis of structurally complex polyketides, the stereochemistry was installed by enantioselective desymmetrization, asymmetric allylations, Evans-Tishchenko reduction, vanadyl-induced epoxidation, Shi epoxidation, Myers alkylation, iodoetherification and aldol reactions as key steps.

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