YOSHIDA Yasuko Nippon Gaishi Ltd., Bio Research, Research Associate, バイオ研究課, 主任研究員
NAKAMURA Kaoru Kyoto Univ., Institute, Associate Professor, 化学研究所, 助教授 (10101239)
|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 1996 : ¥5,300,000 (Direct Cost : ¥5,300,000)
Fiscal Year 1995 : ¥7,600,000 (Direct Cost : ¥7,600,000)
1. Synthesis of Bis (hydroxymethyl)  thiaheterohelicene :
We designed a thiaheterohelicene with two hydroxy groups at the terminal aromatic nuclei and synthesized racemic 2,13-bis (hydroxymethyl) dithieno [3,2-e : 3', 2'-e'] benzo [1,2-b : 4,3-b'] bis  benzothiophene from readily available 1-hydroxymethyl [1,2-b : 4,3-b'] benzo-dithiophene.
2. Molecular Structure and Crystal Packing of Bis (hydroxymethyl)  thia-heterohelicene :
The molecular structure and the crystal packing of racemic  helicenediol was determined by X-ray analysis. The  helicenediol has C_2 symmetry, and ethanol molecule was included in the crystals in a ratio  helicenediol : ethanol=1 : 1 by intermolecular hydrogen bonds. In the crystal cell, the helicenes possessing same helicity (P or M) are aligned in a stacking column along b axis of the crystal.
3. Optical Resolution of Helicenediol by Lipase-catalyzed Transesterification :
The reaction of racemic  helicenediol (100mg) with the lipase from Pseudo
monas cepacia (Amano PS,2.99g) in dichloromethane (100ml) in the presence of molecular sieves 4A (4.37g) at room temperature was terminated close to the 50% esterification point (25h), giving (P) - (+) -  helicenediol (44.7mg, 45% yield) in 98% ee and the corresponding monoacetate (40.9mg, 38% yield) and diacetate (15.1mg, 13% yield) which were readily separated by silica gel chromatography. The rotational value of (P) - (+) -  helicenediol was [alpha] _D +1973 (c0.055, CHCl_3). Hydrolysis of the monoacetate by NaOH in methanol gave (M) - (-) -  helicenediol with 80% ee and the diacetate gave the same enantiomer with 95% ee. In contrast, the transesterification of the racemic  helicenediol (100mg) with the lipase from Candida antarctica (Nova CAL, 0.5g) gave (M) - (-) - bis (hydroxymethyl)  thiaheterohelicene (43.7mg, 44%yield) with 92% ee and the corresponding monoacetate (57.8mg, 53% yield) and diacetate (3.4mg, 3% yield). The rotational value of (M) - (-) -  helicenediol was [alpha]_D -1965 (c0.050, CHCl_3). Less