Synthetic Studies on Shellfish Toxin Azaspiracid
| Project/Area Number |
17510173
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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 |
Living organism molecular science
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| Research Institution | Tohoku University |
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Principal Investigator |
OIKAWA Masato Tohoku University, Tohoku University, Graduate School of Life Sciences, Associate Professor (70273571)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,710,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | synthetic organic chemistry / total synthesis / hapten / natural products chemistry / shellfish toxin |
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| Research Abstract |
Azaspiracid-1 (AZA-1) is a causative toxin for a new type of shellfish poisoning syndrome named azaspiracid poisoning (AZP), prevailed since November 1995 at a coastal region in Europe. After isolation and structural elucidation by a group led by Yasumoto and Satake at Tohoku University in 1998, the first total synthesis and the structural revision of AZA-1 were made by the Nicolaou group in 2004. We have been working toward a synthesis of AZA-1 to prepare haptens used for development of antibodies for the shellfish toxin.
Initially, we have synthesized a C21-C40 EFGHI-ring fragment as follows. The synthesis of the fragment strated with a coupling between a C32-C40 dithiane and a C28-C35 epoxide, prepared from known meso-2, 4-dimethyl-1, 5-pentanediol and D-glutamic acid, respectively. Manipulations of the protecting groups and subsequent spiroaminal formation using a catalytic amount of Yb(Otf)_3 delivered the desired spiroaminal corresponding to the HI-ring fragment stereoselectively. After leading to a C28-C40 aldehyde, the key coupling reaction with an E-ring allylic stannane was carried out by using InCl_3 to afford homoallylic alcohol in good yield. Finally, FG-ring was constructed by the action of HF-pyridine to accomplish the synthesis of a suitably protected C21-C40 fragment of AZA-1. The total yield was 0.025% for the longest linear pathway from D-glutamic acid (37 steps).
The synthetic pathway was then modified for the synthesis of haptens; 1) the protecting group for the C40 amino functionality was optimized to a 2-(trimethylsilyl) ethyl carbamate, and 2) a n-hexyl linker between the AZA-1 fragment and proteins (such as BSA) was determined to be introduced using an α-sulfonylpyran coupling methodology before construction of the C27-C28 bond. The synthetic study is now in the final stage toward the goal.
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Report
(4 results)
Research Products
(27 results)
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[Presentation] Synthetic study of azaspiracid-12007
Author(s)
M. Oikawa ed. al.
Organizer
American Chemical Society 234th National Meeting and Exposition
Place of Presentation
Boston, Massachusetts, USA.
Year and Date
2007-08-19
Description
「研究成果報告書概要(欧文)」より
Related Report
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