TY - JOUR
T1 - Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues
AU - Doi, Takayuki
N1 - Funding Information:
Acknowledgments This study could not have been conducted without the extensive efforts of my colleague, Dr. Yoshitaka Numajiri (at present with Toray Industries, Inc.). I thank all co-workers cited in the references, especially Professor Takashi Takahashi (Yokohama College of Pharmacy), who supported my research at Tokyo Tech. I also thank Professor Kou Hiroya (at present with Musashino University), Dr. Kiyofumi Inamoto, Dr. Masahito Yoshida, Dr. Hirokazu Tsukamoto, Dr. Yuichi Masuda, and all students of the Han-nou Laboratory at Tohoku University. This study was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Nos. 14103013 and 23310145); a Grant-in-Aid for Scientific Research on Innovative Area (No. 2105); and the Naito Foundation. I deeply thank my friends at the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences at Okayama Univ. and at the School of Pharmaceutical Sciences at the Univ. of Shizuoka for the voluntary food aid right after the Great East Japan Earthquake. I appreciate very kind personal support from the Tsuji–Yamamoto–Takahashi group members (Tokyo Tech). I am also grateful for the financial support not only from MEXT but also from many countries in the world for helping in the recovery from damage by the earthquake.
Funding Information:
This study could not have been conducted without the extensive efforts of my colleague, Dr. Yoshitaka Numajiri (at present with Toray Industries, Inc.). I thank all co-workers cited in the references, especially Professor Takashi Takahashi (Yokohama College of Pharmacy), who supported my research at Tokyo Tech. I also thank Professor Kou Hiroya (at present with Musashino University), Dr. Kiyofumi Inamoto, Dr. Masahito Yoshida, Dr. Hirokazu Tsukamoto, Dr. Yuichi Masuda, and all students of the Hannou Laboratory at Tohoku University. This study was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Nos. 14103013 and 23310145); a Grant-in-Aid for Scientific Research on Innovative Area (No. 2105); and the Naito Foundation. I deeply thank my friends at the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences at Okayama Univ. and at the School of Pharmaceutical Sciences at the Univ. of Shizuoka for the voluntary food aid right after the Great East Japan Earthquake. I appreciate very kind personal support from the Tsuji-Yamamoto-Takahashi group members (Tokyo Tech). I am also grateful for the financial support not only from MEXT but also from many countries in the world for helping in the recovery from damage by the earthquake.
Publisher Copyright:
© 2014 The Pharmaceutical Society of Japan.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.
AB - This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.
KW - Cyclodepsipeptide
KW - Cytotoxicity
KW - Natural product
KW - Solid-phase synthesis
KW - Thiazoline
KW - Total synthesis
UR - http://www.scopus.com/inward/record.url?scp=84906545623&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906545623&partnerID=8YFLogxK
U2 - 10.1248/cpb.c14-00268
DO - 10.1248/cpb.c14-00268
M3 - Review article
C2 - 25087625
AN - SCOPUS:84906545623
VL - 62
SP - 735
EP - 743
JO - Chemical and Pharmaceutical Bulletin
JF - Chemical and Pharmaceutical Bulletin
SN - 0009-2363
IS - 8
ER -
