2007 Fiscal Year Final Research Report Summary
Total Synthesis for Elucidation of Structure - Activity Relationships of Antiviral Fattiviracin
| Project/Area Number |
17590011
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
KAJI Eisuke Kitasato University, School of Pharmacy, Professor (60050598)
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| Co-Investigator(Kenkyū-buntansha) |
YAGO Kazuo Kitasato University, School of Pharmacy, Professor (10276157)
NISHINO Takashi Kitasato University, School of Pharmacy, Junior Associate Professor (50180625)
OTORI Katsuya Kitasato University, School of Pharmacy, Junior Associate Professor (00327446)
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| Project Period (FY) |
2005 – 2007
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| Keywords | antiviral agent / antibiotic / fattiviracin / sugar fatty acid / cyclic diester / glucose / glycosylation / cross metathesis |
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| Research Abstract |
Aiming at elucidation of structure-activity relationships of antiviral agent fattiviracins (FVs), we investigated a total synthesis of FV and the related compounds. According to the retro-synthetic pathway proposed for total synthesis of FV possessing C2-symmetric axis, we first endeavored to synthesize a cyclic dimmer of sugar-fatty acid monomer comprising the common core unit of FVs.
Based on this strategy, D-glucose was converted into 2, 3, 4, 6-tetra-O-acetyl-u-D-glucopyranosyl bromide (1) and its trichloroacetimidate analog (2) as reactive glycosyl donors. For glycosyl acceptors we prepared ethyl (3b)-3, 4-dihydroxy-butanoate (3) starting from L-malic acid and an alternative acceptor, t-butyl (3R)-3-hydroxy-4-pentenoate (4) by means of enzymatic acetylation using PS Amano lipase DI as the key reaction.
Of the glycosyl fatty acids being synthesized from various combination of glycosyl donors and acceptors described above, the most promising glycosyl fatty acid monomer seemed to be t-butyl (3R)-3-O-(2, 3, 4, 6-tetra-O-acetyl-(3-D-glucopyranosyl)-4-pentenoate (5), which has been synthesized by glycosylation of 4 with 3 in 60% yield. Compound 5 was subsequently converted into the precursor, (3R) 3 O-(3'0-benzyl-(3-D-glucopyranosyl)-4-pentenoic acid (6), which has been successfully condensed into the common core structure of FV, a cyclic glycosylfatty acid ester (7) in 40% yield.
Furthermore, the compound 7 was exposed to Grubbs conditions to afford side chain-elongated analog 8 in reasonable yield. This methodology may be applicable to the total synthesis of FV and providing the analogs for elucidation of structure-activity relationships.
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Research Products
(4 results)
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[Journal Article] Synthesis of the Central Core Unit of Fattiviracins, a cyclic Dimer of Glucosyl Fatty Acid2008
Author(s)
Eisuke, Kaji, Takashi, Nishino, Tatsuya, Shirahata, Tomomi, Katoh, Teruaki, Komori
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Journal Title
Tetrahedron Lett (in preparation)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Synthesis of Glycosyl Fatty Acid Esters, Constituens of Antibiotic Fattiviracins2008
Author(s)
Teruaki, Komori, Tomomi, Katoh, Tatsuya, Shirahata, Takashi, Nishino, Eisuke, Kaji
Organizer
The 128th Annual Meeting of Pharmaceutical Society of Japan
Place of Presentation
Yokohama
Year and Date
20080300
Description
「研究成果報告書概要(欧文)」より
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