Enantio- and diastereoselective stepwise cyclization of polyprenoids induced by chiral and achiral LBAs. A new entry to (-)-ambrox, (+)-podocarpa-8,11,13-triene diterpenoids, and (-)-tetracyclic polyprenoid of sedimentary origin.
An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Brønsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2'-hydroxy-1,1'-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF(3)CO(2)H.SnCl(4) as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn.SnCl(4). Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn.SnCl(4) and subsequent diastereoselective cyclization induced by BF(3).Et(2)O/EtNO(2) or CF(3)CO(2)H .SnCl(4).
Ishihara
Kazuaki
K
Graduate School of Engineering, Nagoya University, SORST, Japan.
Ishibashi
Hideaki
H
Yamamoto
Hisashi
H
D004224:Diterpenes / Q000138:chemical synthesis*; D005663:Furans / Q000138:chemical synthesis*; D009281:Naphthalenes / Q000138:chemical synthesis*; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000737:chemistry*
D004224:Diterpenes; D005663:Furans; D009281:Naphthalenes; D011083:Polycyclic Compounds; D014212:Tretinoin; C413580:ambrox; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid