Synthesis of NH006--a photostable fungicide effective against Botrytis cinerea--according to the asymmetric total synthesis of MK8383.
MK8383, isolated from Phoma sp. T2526 in 1993, exhibits potent antibiotic activities against a variety of phytopathogens and has been considered a promising fungicide against Botrytis cinerea. Unfortunately, MK8383 is a photosensitive compound and it undergoes irreversible decomposition. Although much effort has been devoted to improving the photostability of MK8383 by chemical modification of its structure by a research group organized by Meiji Seika Kaishya, Ltd. and Mitsubishi Chemical Corporation, a photostable MK8383 derivative has never been prepared. We have found that a C13-14 double bond of MK8383 and (+)-phomopsidin is responsible for the photosensitivity, and herein, we report the synthesis of NH006, an MK8383 derivative with a saturated C13-14 double bond and (S) configuration at C14, based on the asymmetric total synthesis of MK8383. NH006 exhibits good photostability and potent antifungal activity against B. cinerea.
Hayashi
Nobuyuki
N
Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Yamamoto
Kentaro
K
Minowa
Nobuto
N
Mitomi
Masaaki
M
Nakada
Masahisa
M
D001203:Ascomycota / Q000737:chemistry*; D020171:Botrytis / Q000187:drug effects*; D018360:Crystallography, X-Ray; D005659:Fungicides, Industrial / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010421:Pentanoic Acids / Q000737:chemistry; D055668:Photochemical Processes; D013764:Tetrahydronaphthalenes / Q000737:chemistry
D005659:Fungicides, Industrial; D010421:Pentanoic Acids; D013764:Tetrahydronaphthalenes; C109724:phomopsidin