TY - JOUR
T1 - Synthesis of a biphenylalanine analogue of apratoxin a displaying substantially enhanced cytotoxicity
AU - Onda, Yuichi
AU - Fukushi, Kazuki
AU - Ohsawa, Kosuke
AU - Yoshida, Masahito
AU - Masuda, Yuichi
AU - Doi, Takayuki
N1 - Funding Information:
This work was supported by JSPS KAKENHI, Grant no. JP15H05837 (Grant-in-Aid for Scientific Research on Innovative Areas: Middle Molecular Strategy), and the Platform Project for Supporting in Drug Discovery and Life Science Research from AMED under Grant No. JP18am0101095 and JP18am0101100. The authors are grateful to Profs. Yoshiteru Oshima and Haruhisa Kikuchi at the Graduate School of Pharmaceutical Sciences in Tohoku University for allowing us to use their facility for the cell-based assay. The authors also thank MARUZEN-YUSHODO Co., Ltd. for the English language editing.
Publisher Copyright:
© 2020 The Japan Institute of Heterocyclic Chemistry.
PY - 2020
Y1 - 2020
N2 - The concise synthesis of the 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid moiety of apratoxin A and the total synthesis of compound 3, a 4-biphenylalanine (Bph) analogue of apratoxin A, have been demonstrated. The Bph analogue 3 exhibited a 16-fold increase in cytotoxicity against HCT-116 cells with respect to apratoxin A. This evidence indicated that existing the 4-phenyl group of Bph in 3 significantly enhanced its cytotoxicity, a conclusion corroborated by the 100-fold difference in cytotoxicity against HCT-116 cells observed between apratoxin M7 and apratoxin M16, which is characterized by the presence of a 4-phenyl group where apratoxin M7 displays a 4-methoxy group. Results from a conformational study using a distance geometry method suggested that 3 and apratoxin A adopt similar conformations in CD3CN.
AB - The concise synthesis of the 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid moiety of apratoxin A and the total synthesis of compound 3, a 4-biphenylalanine (Bph) analogue of apratoxin A, have been demonstrated. The Bph analogue 3 exhibited a 16-fold increase in cytotoxicity against HCT-116 cells with respect to apratoxin A. This evidence indicated that existing the 4-phenyl group of Bph in 3 significantly enhanced its cytotoxicity, a conclusion corroborated by the 100-fold difference in cytotoxicity against HCT-116 cells observed between apratoxin M7 and apratoxin M16, which is characterized by the presence of a 4-phenyl group where apratoxin M7 displays a 4-methoxy group. Results from a conformational study using a distance geometry method suggested that 3 and apratoxin A adopt similar conformations in CD3CN.
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U2 - 10.3987/COM-19-S(F)35
DO - 10.3987/COM-19-S(F)35
M3 - Article
AN - SCOPUS:85078500507
SN - 0385-5414
VL - 101
SP - 679
EP - 691
JO - Heterocycles
JF - Heterocycles
IS - 2
ER -