2007 Fiscal Year Final Research Report Summary
Screeing of novel microbial- and enzyme catalysts for expeditious chemical synthesis of useful substances
| Project/Area Number |
18580106
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bioproduction chemistry/Bioorganic chemistry
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
SUGAI Takeshi Keio University, Chemistry, Associate Professor (60171120)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | organic chemistry / bioreactor / enzymes / applied microbiology |
|---|
| Research Abstract |
Based on the chemo-enzymatic synthesis with complementary use of organic synthesis and enzyme-catalyzed transformation, the following researches were accomplished.
1) Screening of microorganisms which can reduce sterically hindered ketones. in enantifacially selective manner
Towards the synthesis of sterically hindered optically active secondary alcohol, yeast strains (Candida floricola IAM 13115 and)-Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone were newly developed by screening. Strains with complementary re-facial selectivity (Pichia angusta IAM 12895 and Pichia minute IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S, 5S)-2, 6-dimethyl-3, 5-heptanediol.
2) Application of newly found yeast strains for the synthesis of naturally occurring bioactive product, such as modiolide A.
While the first total synthesis of modiolide A, a ten-membered ring lactone with a marine-origin was achieved, an important chiral building block for constructing the chirality at C-4, (S)-6-[(4-methoxybenzyl)oxy]-1-trimethylsilyl-1-hexyn-3-ol was obtained in as high as 96.1% ee. Asymmetric reduction of a silylated propargyl ketone mediated by whole-cell of Pichia minute IAM 12215 was established.
3) Delopment of Bacillus subtilis epoxide hydrolase in organic syntheses.
An expeditious route for the enantiopure 2-methylpropane-1, 2, 3-triol monobenzyl ether was examined. An engineered Bacillus subtilis epoxide hydrolase worked enantioselectively on a racemic epoxide to provide the desired product in highly enantiomerically enriched state.
|
-
[Journal Article] Bacillus subtilis epoxide hydrolase-catalyzed preparation of enantiopure 2-methylpropane-1,2,3-triol monobenzyl ether and its application to expeditious synthesis of(R)-bicalutamide2007
Author(s)
A.Fujino, M.Asano, H.Yamaguchi, N.Shirasaka, A.Sakoda, M.Ikunaka, R.Obata, S.Nishiyama, T.Sugai
-
Journal Title
Tetrahedron Letters 48
Pages: 979-983
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
-
-
[Journal Article] Bacillus subtilis epoxide hydrolase-catalyzed preparation of enantiopure 2-methylpropane-1, 2, 3-triol monobenzyl ether and its application to expeditious synthesis of (R)-bicalutamide2007
Author(s)
A., Fujino, M., Asano, H., Yamaguchi, N., Shirasaka, A., Sakoda, M., Ikunaka, R., Obata, S., Nishiyama, T., Sugai
-
Journal Title
Tetrahedron Lett 48
Pages: 979-983
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Screening,substrate specificity and stereoselectivity of yeast strains,which reduce sterically hindered isopropyl ketones2006
Author(s)
C.Hiraoka, M.Matsuda, Y.Suzuki, S.Fujieda, M.Tomita, K.Fuhshuku, R.Obata, S.Nishiyama, T.Sugai
-
Journal Title
Tetrahedron:Asymmetry 17
Pages: 3357-3368
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
-
[Journal Article] Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones2006
Author(s)
C., Hiraoka, M., Matsuda, Y., Suzuki, S., Fujieda, M., Tomita, Fuhshuku, R., Obata, S., Nishiyama, T., Sugai
-
Journal Title
Tetrahedron : Asymmetry 17
Pages: 3357-3368
Description
「研究成果報告書概要(欧文)」より
-
-
-
