Enantioselective Synthesis of Unsymmetrically-Substituted Organophosphorus Compounds with Stereogenic Phosphorus Atoms
| Project/Area Number |
08454200
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Organic chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
HAYAKAWA Yoshihiro Graduate School of Human Informatics, Professor, 大学院・人間情報学研究科, 教授 (50022702)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Sizuaki Graduate School of Human Informatics, Associate Professor, 大学院・人間情報学研究科, 助教授 (50157781)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | asymmetric synthesis / optically active imidazole / optically active tetrazoles / dynamic kinetic resolution / phosphoramidite method / DNA synthesis / acid / base complex-type promoter / antisense nucleic acid / DNA合成 / 光学活性リン酸エステル / 光学活性アゾール / ヌクレオチドホスホロチオエ-ト / 酸 / 塩基複合活性化剤 / ホスホロアミダイト / アミダイト法 |
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| Research Abstract |
Asymmetric synthesis of optically active organophosphorus compounds via the phosphoramidite method using an optically active promoter, where the enantioselection is caused by kinetic resolution of the intermediates, was investigated. A number of enantioselective syntheses of an unsymmetrically substituted trialkyl phosphite were attempted using an optically pure tetrazole compound such as (R) - (-) -2-methoxy-2'- (1H-tetrazol-5-yl) -l, l'-binaphthyl or (lR, 2R) - (+) - 1-trimethylsilyl-2- (1H-tetrazol-5-yl) ferrocene, or an optically pure imidazole derivative such as (S)- 1 - [2- (6-methoxynaphthyl) ] -1- (2-benzimidazolyl) ethane or (S) -l- (2- imidazolyl) -l- (tert-butyldimethylsiloxy) ethane as the promoter. However, little selectivity was observed in all attempts.
Although the intended objective has not been achieved, this research disclosed that imidazole triflate and benzimidazolium triflate serve as highly reactive promoters in the synthesis of oligonucleotides via the phosphoramidite approach. Particularly, imidazole triflate is a useful reagent which allows 0-selective phosphitylation, i.e, intemucleotide-linkage formation of N-unprotected nucleosides and has opened an ideal synthesis of oligodeoxyribonucleotides without nucleoside-base protection. This novel method allows low-cost supply of the products and accordingly will be useful for large-scale synthesis of DNA-related compounds including DNA phosphorothioates important as antisense molecules.
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Report
(4 results)
Research Products
(39 results)
