Asymmetric Synthesis with Chiral Nucleophilc Catalysts
| Project/Area Number |
11470468
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
KAWABATA Takeo Kyoto University, Institute for Chemical Research, Associate Professor, 化学研究所, 助教授 (50214680)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
|
|---|
| Keywords | nucleophilic catalyst / kinetic resolution / hydrogen bonding / substrate-specificity / acceleration / π-π interaction / meso-diol / proline / 求核触媒 / ペプチド / ラクトン化 / induced fit / プロリン / ヒドロキシプロリン / アミノアルコール / PPY / DMAP |
|---|
| Research Abstract |
A chiral nucleophilic catalyst, 4-pyrrolidinopyridine (PPY) analogue, has been developed which could effectively catalyze the acylative kinetic resolution racemic amino alcohol derivatives with selectivity factors of 10 to 54. Kinetic studies of acylation indicated that the observed high enantioselectivity of the acylation promoted by the catalyst is due to the rate acceleration of acylation of one enantiomer rather than the rate deceleration of the other. The origin of the acceleration was revealed to be due to the transition state-hydrogen bonding between a substrate and the catalyst.
Chiral PPY analogues were also readily prepared from L-proline. Although these catalysts do not possess chiral elements near the catalytically active pyridine-nitrogen, they promote kinetic resolution of racemic alcohols highly selectively. Contrary to the mechanism of enantioselective acylation by the previously PPY analogue, π-π interaction between an aromatic ring and pyridinium π-system is critical in the chiral nucleophilic catalysts derived from L-proline. A new generation of chiral nucleophilic catalysts with dual functional side chains was successfully prepared from 4-hydroxy-L-proline. These catalysts showed superior chemo- and enantioselectivity in asymmetric desymmetrization of meso-diols.
|
Report
(4 results)
Research Products
(18 results)
