2006 Fiscal Year Final Research Report Summary
Synthetic Studies of the Marine Alkaloids, Madangamines with Anti Tumor Activities
| Project/Area Number |
15590025
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Sciences |
|---|
Principal Investigator |
YAMAZAKI Naoki Tokyo University of Pharmacy and Life Sciences, 薬学部, 講師 (30277264)
|
|---|
| Project Period (FY) |
2003 – 2006
|
| Keywords | marine alkaloid / madangamine / macrocyclization / cross-coupling reaction / N, O-acetalization / hydrogenation of bridge head iminium ion / intramolecular reductive amination / anti tumor activities |
|---|
| Research Abstract |
Madangamine A is a pentacyclic alkaloids that was isolated from the marine sponge Xestospongia ingens by Andersen in 1994. Soon after, new constituents of this alkaloid type, madangamines B-E, were isolated from the same organism. Madangamine A exhibits cytotoxic activities against P388, A549, U373, and MCF-7 tumor cell lines. In this research project, I have accomplished the construction of the ABC and ACE-ring frameworks of madangamines. N, O-Acetalization of the keto-aminophenol allows rapid construction of the 2-azabicyclo[3.3.1]nonane skeleton with a quaternary carbon center at C4. This strategy enabled the stereoselective construction of the central diazatricyclic core (ABC-ring) of the madangamine alkaloids. In the next stage of our investigation, an efficient construction of the madangamine tricyclic ring, 4-azatricyclo[11.2.2.0^<4.14>]heptadec-12-ene, including an 11-membered macrocycle (ACE-ring) has been accomplished via construction of the 2-azabicyclo[3.3.1]nonane skeleton by N, O-acetalization of a cyclohexanone derivative, geometry-retained cross-coupling reaction, and intramolecular reductive amination. From the results obtained above, my future studies will be focused on the construction of a 15-membered macrocycle (D-ring) for the total synthesis of madangamines.
|
Research Products
(6 results)
-
[Journal Article] Synthesis of the 11-Membered Ring of the Marine Alkaloids, Madangamines2006
Author(s)
Yoshimura, Y., Inoue, J., Yamazaki, N., Aoyagi, S., Kibayashi, C.
-
Journal Title
Tetrahedron Letters 47
Pages: 3489-3492
Description
「研究成果報告書概要(和文)」より
-
-
-
-
-
