1987 Fiscal Year Final Research Report Summary
Synthetic studies on macrolide antibiotics through the cyclic polyketides.
| Project/Area Number |
61470090
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
有機工業化学
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| Research Institution | Faculty of Science and Technology, Keio University |
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Principal Investigator |
TATSUTA KUNIAKI Faculty of Science and Technology, Kieo University, 理工学部, 教授 (40051627)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Biosynthesis / Macrolide / Antibiotics / Stereospecific Synthesis / Stereoselctive Reduction / Ruthenium Oxidation / 大環状化合物 / 主体配座規制 |
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| Research Abstract |
The problem of when and how the secondary hydroxy group stereochemistry is controlled remains one of the most challenging aspects of the macrolide biosynthesis.
Here will be described the synthetic studies on macrolide antibiotics, especially, oleandolides, from the cyclic polyketide (polyketide lactone) as a chemical simulation.
An aglycone of oleandomycin, (8R,9S)-9-dihydro-8-methyloleandolide (1) was obtained in a good yield from oleandomycin in 6 steps through removal of the amino sugar moiety by treatment of the N-oxide with trimethylsilyl iodide. Exhaustive oxidation of the four hydroxy groups in 1 was realized by exposure to RuO_4 in CCl_4 to give the polyketide lactone (M^+ 366). The reduction of th epolyketide was achieved by Zn (BH_4)_2 in the presence of MgBr_2 to provide stereoselectively the tetraol as cubes in 80% yeild. The absolute structure was defined by the X-ray analysis to be (5R,8R,9R)-9-dihydro- 8-methyl-epi-oleandolide (2), the stereochemistry of which was incompatible with that of the natural macrolide only at the C-5. The reduction, however, withour MgBr2 gave a 1:1 mixture of the natural 1 and 5-epi-oleandolide 2.
On the other hand, the C-9 ketone, which was obtained from 1 by selective benzylidenation and oxidation, was led to the biosynthetic precursor, 8-methyl- oleandolide, by catalytic hydrogenation.
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