| Budget Amount *help |
¥3,740,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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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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