Formal total synthesis of (+)-macrosphelide A based on regioselective hydrolysis using lipase.
Three kinds of seco-macrosphelide A congeners, (4R,5S,10R,11S,15S)-6, (4R,5S,9S,14R,15S)-7 and (3S,8R,9S,14R,15S)-8 were chemically synthesized, and they were exposed to the lipase OF-360 from Candida rugosa to give three hydroxy carboxylic acids, respectively. Macrolactonization of the hydroxy acid (4R,5S,10R,11S)-18 derived from (4R,5S,10R,11S,15S)-6 gave 12-membered lactone (19) in 47% overall yield from 6, while that of the seco-acid (4) derived from (4R,5S,9S,14R,15S)-7 afforded (-)-dibenzyl macrosphelide A (25) in 27% overall yield from 7. Macrolactonization of the hydrolysis product, seco-acid (5) derived from (3S,8R,9S,14R,15S)-8, provided (-)-dibenzyl macrosphelide A (25) (5% overall yield from 8) and 12-membered lactone (19) (20% overall yield from 8) concurrently.
Ono
Machiko
M
School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan.
Nakamura
Hiroshi
H
Arakawa
Satoko
S
Honda
Naoko
N
Akita
Hiroyuki
H
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006868:Hydrolysis; D007783:Lactones / Q000737:chemistry; D008049:Lipase / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D006571:Heterocyclic Compounds; D007783:Lactones; C097798:macrosphelide A; D008049:Lipase