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Syntheses and biological evaluation of BE-43547A2 analogues modified at O35 ester and C15-OH sites |
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| Authors: | Yuanjun Sun Ruifei Zhou Honglei Xu Dehong Wang Xiuwen Su Chao Wang Yahui Ding Liang Wang Yue Chen |
| Institution: | 1. The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, PR China;2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, PR China;3. Department of Chemistry, Yale University, New Haven, CT, 06520, United States |
| Abstract: | Total syntheses of 6 BE-43547A2 analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A2 delivered 15-epi-BE-43547A2, which verified the proposition that the C15 is an active site for late stage oxidation. The N35 and C15-F of analogues 1b and 1d were synthesized. Cellular level tests indicated O35 is a prohibitive site for modification and substitution of the OH at C15 with F or trim of the OH both led to a dramatic loss of activity. Compound 1e showed comparable inhibitory level towards Panc-1?cells, which indicated that the OH at C15 are permissive site for further modifications. |
| Keywords: | Structure-activity relationship BE-43547 Anticancer Hypoxia Total synthesis |
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