Syntheses and biological evaluation of BE-43547A                         2                          analogues modified at O35 ester and C15-OH sites

Yuanjun Sun; Ruifei Zhou; Honglei Xu; Dehong Wang; Xiuwen Su; Chao Wang; Yahui Ding; Liang Wang; Yue Chen

doi:10.1016/j.tet.2018.12.053

Syntheses and biological evaluation of BE-43547A ₂ analogues modified at O35 ester and C15-OH sites

Yuanjun Sun
, Ruifei Zhou
, Honglei Xu
, Dehong Wang
, Xiuwen Su
, Chao Wang
, Yahui Ding
, Liang Wang
, Yue Chen^*

^*Corresponding author for this work

Nankai University
Yale University
Collaborative Innovation Center of Chemical Science and Engineering

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Total syntheses of 6 BE-43547A ₂ analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A ₂ delivered 15-epi-BE-43547A ₂ , 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.

Original language	English
Pages (from-to)	1808-1818
Number of pages	11
Journal	Tetrahedron
Volume	75
Issue number	12
DOIs	https://doi.org/10.1016/j.tet.2018.12.053
Publication status	Published - 22 Mar 2019
Externally published	Yes

Keywords

Anticancer
BE-43547
Hypoxia
Structure-activity relationship
Total synthesis

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10.1016/j.tet.2018.12.053

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@article{4f7eda143ca44f37ab524ad4dbe387f0,

title = " Syntheses and biological evaluation of BE-43547A 2 analogues modified at O35 ester and C15-OH sites ",

abstract = " Total syntheses of 6 BE-43547A 2 analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A 2 delivered 15-epi-BE-43547A 2 , 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 = "Anticancer, BE-43547, Hypoxia, Structure-activity relationship, Total synthesis",

author = "Yuanjun Sun and Ruifei Zhou and Honglei Xu and Dehong Wang and Xiuwen Su and Chao Wang and Yahui Ding and Liang Wang and Yue Chen",

note = "Publisher Copyright: {\textcopyright} 2018",

year = "2019",

month = mar,

day = "22",

doi = "10.1016/j.tet.2018.12.053",

language = "English",

volume = "75",

pages = "1808--1818",

journal = "Tetrahedron",

issn = "0040-4020",

number = "12",

}

Syntheses and biological evaluation of BE-43547A ₂ analogues modified at O35 ester and C15-OH sites . / Sun, Yuanjun; Zhou, Ruifei; Xu, Honglei et al.
In: Tetrahedron, Vol. 75, No. 12, 22.03.2019, p. 1808-1818.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Syntheses and biological evaluation of BE-43547A 2 analogues modified at O35 ester and C15-OH sites

AU - Sun, Yuanjun

AU - Zhou, Ruifei

AU - Xu, Honglei

AU - Wang, Dehong

AU - Su, Xiuwen

AU - Wang, Chao

AU - Ding, Yahui

AU - Wang, Liang

AU - Chen, Yue

PY - 2019/3/22

Y1 - 2019/3/22

N2 - Total syntheses of 6 BE-43547A 2 analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A 2 delivered 15-epi-BE-43547A 2 , 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.

AB - Total syntheses of 6 BE-43547A 2 analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A 2 delivered 15-epi-BE-43547A 2 , 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.

KW - Anticancer

KW - BE-43547

KW - Hypoxia

KW - Structure-activity relationship

KW - Total synthesis

UR - https://www.scopus.com/pages/publications/85059521272

U2 - 10.1016/j.tet.2018.12.053

DO - 10.1016/j.tet.2018.12.053

M3 - Article

AN - SCOPUS:85059521272

SN - 0040-4020

VL - 75

SP - 1808

EP - 1818

JO - Tetrahedron

JF - Tetrahedron

IS - 12

ER -

Syntheses and biological evaluation of BE-43547A ₂ analogues modified at O35 ester and C15-OH sites

Abstract

Keywords

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