2007 Fiscal Year Final Research Report Summary
Synthetic Studies on Shellfish Toxin Azaspiracid
| Project/Area Number |
17510173
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Living organism molecular science
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
OIKAWA Masato Tohoku University, Tohoku University, Graduate School of Life Sciences, Associate Professor (70273571)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Keywords | synthetic organic chemistry / total synthesis / hapten / natural products chemistry / shellfish toxin |
|---|
| 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.
|
Research Products
(25 results)
