Desymmetrization Strategy: Synthesis of Right Segment of Ingramycin

doi:10.6023/cjoc202006067

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (1): 364-369.DOI: 10.6023/cjoc202006067 Previous Articles Next Articles

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去对称化策略合成Ingramycin右部片断

孙默然^a^,^b, 白磊阳^a^,^b, 向俊鸿^a^,^b, 杨华^a^,^b, 于德泉^a, 刘宏民^a^,^b^,^*()

a 郑州大学药学院郑州 450001
b 新药创制与药物安全性评价河南省协同创新中心郑州 450001

收稿日期:2020-06-29 修回日期:2020-07-23 发布日期:2020-08-18
通讯作者: 刘宏民
作者简介:
* Corresponding author. E-mail: liuhm@zzu.edu.cn
基金资助:
国家自然科学基金(21372205); 国家自然科学基金(21302175); 河南省科技厅基础研究(132300410028)

Desymmetrization Strategy: Synthesis of Right Segment of Ingramycin

Moran Sun^a^,^b, Leiyang Bai^a^,^b, Junhong Xiang^a^,^b, Hua Yang^a^,^b, Dequan Yu^a, Hongmin Liu^a^,^b^,^*()

a School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001
b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001

Received:2020-06-29 Revised:2020-07-23 Published:2020-08-18
Contact: Hongmin Liu
Supported by:
the National Natural Science Foundation of China(21372205); the National Natural Science Foundation of China(21302175); the Basic Research Project of Science and Technology Department of Henan Province(132300410028)

In the construction of chiral tertiary alcohol of the natural product ingramycin, the conventional asymmetric synthesis and the method that using the chiral source as material were not used. Instead, exploring the symmetry of natural product itself, the symmetric nonchiral precursor was synthesized firstly, and then the selective ester hydrolysis reaction under lipase catalysis was carried out, which not only promoted the transformation of functional groups, but also constructed a challenging and sterically congested quaternary carbon stereocenter. Based on the readily available allyl bromide and ethyl acetate, the right segment of ingramycin was synthesized by 11 steps with total yield of 26.7% and ee value of 50.84%.

Key words: ingramycin, desymmetrization, lipase, chiral tertiary alcohol

Cite this article

Moran Sun, Leiyang Bai, Junhong Xiang, Hua Yang, Dequan Yu, Hongmin Liu. Desymmetrization Strategy: Synthesis of Right Segment of Ingramycin[J]. Chinese Journal of Organic Chemistry, 2021, 41(1): 364-369.

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脂肪酶	13 ^a		14 ^b
脂肪酶	$[\alpha]_{D}^{20}$	Yield/%	$[\alpha]_{D}^{20}$	ee/%
解脂假丝酵母	–2.5	69	+5.9	50.84
猪胰脂肪酶	–2.8	56	+2.4	26.43
牛胰脂肪酶	–1.5	51	+2.8	27.01
米曲霉脂肪酶	–1.3	47	+1.7	20.30

脂肪酶	13 ^a		14 ^b
脂肪酶	$[\alpha]_{D}^{20}$	Yield/%	$[\alpha]_{D}^{20}$	ee/%
解脂假丝酵母	–2.5	69	+5.9	50.84
猪胰脂肪酶	–2.8	56	+2.4	26.43
牛胰脂肪酶	–1.5	51	+2.8	27.01
米曲霉脂肪酶	–1.3	47	+1.7	20.30

去对称化策略合成Ingramycin右部片断

Desymmetrization Strategy: Synthesis of Right Segment of Ingramycin

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