Synthesis of the Epimer of Pericosine B from (‐)‐Quinic Acid.

Abstract

Synthesis of the Epimer of Pericosine B from (-)-Quinic Acid. -A stereoselective synthesis of the C-6 epimer of pericosine B is presented. The cytotoxic activity of this epimer (I) is lower than that of pericosine B. -(USAMI*, Y.; HATSUNO, C.; YAMAMOTO, H.; TANABE, M.; NUMATA, A.; Chem.

Natural pericosines B and C as enantiomeric mixtures: Direct evidence by chiral HPLC analysis

“…Racemic 2 and 3 were synthesized following the procedures used in our previous work with some modifications, as summarized in Scheme 17, 20, 21. A diastereomeric mixture of the Diels‐Alder adducts between furan and methyl acrylate23 was exo‐face selectively dihydroxylated to afford rac ‐ 6 .…”

“…A diastereomeric mixture of the Diels‐Alder adducts between furan and methyl acrylate23 was exo‐face selectively dihydroxylated to afford rac ‐ 6 . rac ‐ 6 was protected to produce cyclohexylidene compound rac ‐ 8 in 93% yield, which was then treated with LHMDS in THF at −78°C to give methyl 5‐epishikimate rac ‐ 9 in 95% yield 17, 24. The synthesis of racemic 3 from rac ‐ 9 was carried out following a known procedure 21.…”

“…The synthesis of racemic pericosines B and C was basically carried out along the lines of our previous work 17, 20, 21. The synthesis of new compounds and the modified procedures are described below.…”

“…1 are structurally unique and highly functionalized C‐7 cyclohexenoid metabolites of Periconia byssoides OUPS‐N133, a fungus originally separated from the sea hare Aplysia kurodai 10, 11. The absolute configuration of pericosines A–D 1 , 2 , 3 , 4 had been elucidated by a series of synthetic studies 12–18. Pericosines A 1 , B 2 , and D 4 exhibit significant in vitro cytotoxicity to P388 murine cell lines.…”

“…In addition to the significant bioactivity mentioned above, it is noteworthy that pericosines C 3 and E 5 exist as enantiomeric mixtures. The difference in specific rotation between natural 3 and synthetic 3 led to the conclusion that 3 is an enantiomeric mixture 11, 17. The relative stereochemistry of 5 was established by X‐ray analysis, suggesting that it is constructed by two monomeric pericosines 1 and 2 with the opposite configuration.…”