Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol.
Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.
Sakurai
Junji
J
Laboratory of Synthetic Medicinal Chemistry, Department of Chemical Pharmaceutical Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
Oguchi
Takamasa
T
Watanabe
Kazuhiro
K
Abe
Hideki
H
Kanno
Syu-ichi
S
Ishikawa
Masaaki
M
Katoh
Tadashi
T
D001685:Biological Factors / Q000138:chemical synthesis* / Q000737:chemistry; D053138:Cyclohexenes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001685:Biological Factors; D053138:Cyclohexenes; D012717:Sesquiterpenes; C455540:aureol; C046374:avarone; C023663:avarol