TY - JOUR
T1 - A double hemiketal formation/hetero-michael addition approach to the [6,5,5]-dispiroketal system of spirolides
AU - Yamakoshi, Hiroyuki
AU - Toita, Akinori
AU - Igari, Toshihiro
AU - Takeda, Keisuke
AU - Hashimoto, Shunichi
AU - Nakamura, Seiichi
N1 - Funding Information:
This research was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED). A.T. is grateful to JSPS for a graduate fellowship.
Publisher Copyright:
© 2017 The Japan Institute of Heterocyclic Chemistry Received.
PY - 2017
Y1 - 2017
N2 - An approach to the [6,5,5]-dispiroketal ring system of spirolides is described. It was found that cisoid isomers, which suffered from a destabilizing dipole-dipole interaction, were preferentially formed over transoid isomers by a double hemiketal formation/hetero-Michael addition sequence regardless of the reaction conditions used. However, the stereochemistry at C12 was controlled by the methyl group at C13, resulting in the preferential formation of undesired 12S isomers. As expected from precedents, the desired isomer could be obtained upon exposure of the 12R isomer, formed by the sequence, to TsOH in benzene, albeit in a ratio of 1:3 favoring its C15-epimer.
AB - An approach to the [6,5,5]-dispiroketal ring system of spirolides is described. It was found that cisoid isomers, which suffered from a destabilizing dipole-dipole interaction, were preferentially formed over transoid isomers by a double hemiketal formation/hetero-Michael addition sequence regardless of the reaction conditions used. However, the stereochemistry at C12 was controlled by the methyl group at C13, resulting in the preferential formation of undesired 12S isomers. As expected from precedents, the desired isomer could be obtained upon exposure of the 12R isomer, formed by the sequence, to TsOH in benzene, albeit in a ratio of 1:3 favoring its C15-epimer.
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U2 - 10.3987/COM-16-S(S)61
DO - 10.3987/COM-16-S(S)61
M3 - Article
AN - SCOPUS:85025448904
SN - 0385-5414
VL - 95
SP - 939
EP - 949
JO - Heterocycles
JF - Heterocycles
IS - 2
ER -