Synthesis, resolution, and absolute stereochemistry of (-)-blestriarene C.
A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.
Hattori
Tetsutaro
T
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07, Aoba-ku, Sendai 980-8579, Japan. hattori@orgsynth.che.tohoku.ac.jp
Shimazumi
Yuhi
Y
Goto
Hitoshi
H
Yamabe
Osamu
O
Morohashi
Naoya
N
Kawai
Wataru
W
Miyano
Sotaro
S
D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010616:Phenanthrenes / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013267:Stilbenes
C468327:1,1'-biphenanthrene; D010616:Phenanthrenes; D013267:Stilbenes; C468328:blestriarene C