TY - JOUR
T1 - The total synthesis and structure-activity relationships of a highly cytotoxic depsipeptide kulokekahilide-2 and its analogs
AU - Takada, Yuuki
AU - Umehara, Masahiro
AU - Katsumata, Ryosuke
AU - Nakao, Yoichi
AU - Kimura, Junji
N1 - Funding Information:
The authors thank Ms. Eriko Mori and Ms. Ei Horii at the Aoyama Gakuin University for support in the synthesis. This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI) (No. 1931013B ) and Strategic Research Foundation Grant-aided Project for Private Universities (No. S0901031 ) from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology (MEXT).
PY - 2012/1/14
Y1 - 2012/1/14
N2 - We successfully completed the total synthesis of kulokekahilide-2, a cytotoxic depsipeptide from the Cephalaspiedean mollusk Phillinopsis speciosa. We have revised the absolute stereochemistry of kulokekahilide-2 to 21-l-Ala, 24-d-MePhe, 37-l-Ile, 43-d-Ala, 15-d-Hica, and 5S,6S,7S-Dtda. We also investigated the cause of the mis-assignment of the configuration in the originally proposed kulokekahilide-2 and concluded that methanolysis using MeONa caused partial racemization, which led to the mis-assignment. The structure-activity relationships of kulokekahilide-2 and its analogs indicate the importance of an l-amino acid at position 21.
AB - We successfully completed the total synthesis of kulokekahilide-2, a cytotoxic depsipeptide from the Cephalaspiedean mollusk Phillinopsis speciosa. We have revised the absolute stereochemistry of kulokekahilide-2 to 21-l-Ala, 24-d-MePhe, 37-l-Ile, 43-d-Ala, 15-d-Hica, and 5S,6S,7S-Dtda. We also investigated the cause of the mis-assignment of the configuration in the originally proposed kulokekahilide-2 and concluded that methanolysis using MeONa caused partial racemization, which led to the mis-assignment. The structure-activity relationships of kulokekahilide-2 and its analogs indicate the importance of an l-amino acid at position 21.
KW - Cyclic depsipeptide
KW - Cytotoxicity
KW - Kulokekahilide-2
KW - Structure-activity relationships
KW - Total synthesis
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U2 - 10.1016/j.tet.2011.10.094
DO - 10.1016/j.tet.2011.10.094
M3 - Article
AN - SCOPUS:82955235549
SN - 0040-4020
VL - 68
SP - 659
EP - 669
JO - Tetrahedron
JF - Tetrahedron
IS - 2
ER -