Stereocontrolled Synthesis of (+)-Negamycin by 1, 3-Asymmetric Induction
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- OHNO Masaji
- Faculty of Pharmaceutical Sciences, University of Tokyo
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- KOBAYASHI Susumu
- Faculty of Pharmaceutical Sciences, University of Tokyo
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- IZAWA Toshio
- Faculty of Pharmaceutical Sciences, University of Tokyo
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- WANG Yi-Fong
- Faculty of Pharmaceutical Sciences, University of Tokyo
Bibliographic Information
- Other Title
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- (+)-ネガマイシンの立体選択的不斉合成
- + ネガマイシン ノ リッタイ センタクテキ フセイ ゴウセイ
- (+)‐ネガマイシンの立体選択的不斉合成
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Abstract
Negamycin, [2-[(3 R, 5R)-3, 6-diamino-5-hydroxyhexanoy1]-1-methylhydrazino]acetic acid, which possesses a strong inhibitory activity against Gram-negative bacteria, has been synthesized in a highly stereocontrolled manner. A combination of enzymatic and chemical procedures was taken as our synthetic strategy.<BR>The 3 R-absolute configuration was created by the enzyme-mediated asymmetric hydrolysis of the prochiral dimethyl 3-(benzyloxycarbonylamino)glutarate. The remaining 5 R-absolute configuration was introduced by the newly developed iodocyclocarbamation with high 1, 3asymmetric induction. Thus, the enzymatically produced chiral half ester, methyl hydrogen (3 S)-3-(benzyloxycarbonylamino)glutarate, was chemically converted to t-buty1(3 R)-3-benzyloxycarbonylamino5-hexenoate in 4 steps, and treatment of the N-(t-butyldimethylsily1)derivative with iodine afforded preferentially trans-cyclic carbamate, effecting high 1, 3-asymmetric induction. Further transformation of the. functional groups efficiently afforded the desired key intermediate, (3 R, 5 R)-6-azido-3-benzyloxycarbonylamino-5-(tetrahydropyran -2yloxy)hexanoic acid, which was then converted to natural negamycin in good overall yields.
Journal
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- NIPPON KAGAKU KAISHI
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NIPPON KAGAKU KAISHI 1983 (9), 1299-1307, 1983-09-10
The Chemical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282679366225408
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- NII Article ID
- 130004157638
- 40002843415
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- NII Book ID
- AN00186595
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- COI
- 1:CAS:528:DyaL2cXosFClsg%3D%3D
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- ISSN
- 21850925
- 03694577
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- NDL BIB ID
- 2604820
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed