Total Synthesis of Praeruptorin E

doi:10.6023/cjoc202407003

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (3): 1009-1020.DOI: 10.6023/cjoc202407003 Previous Articles Next Articles

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白花前胡素E的全合成研究

白磊阳, 付蓓, 刘海平, 淳享, 姜雪峰^*()

华东师范大学化学与分子工程学院上海市绿色化学与化工过程绿色化重点实验室上海 200062

收稿日期:2024-07-02 修回日期:2024-08-14 发布日期:2024-09-30
通讯作者: 姜雪峰
基金资助:
国家自然科学基金(22125103); 上海市基础研究领域项目(22JC1401000); 中国博士后科学基金(2023M731094); 中国博士后科学基金(BX20230127)

Total Synthesis of Praeruptorin E

Leiyang Bai, Bei Fu, Haiping Liu, Xiang Chun, Xuefeng Jiang()

School of Chemistry and Molecular Engineering, Shanghai Key Laboratory of Green Chemistry and Chemical Progress, East China Normal University, Shanghai 200062

Received:2024-07-02 Revised:2024-08-14 Published:2024-09-30
Contact: Xuefeng Jiang
Supported by:
National Natural Science Foundation of China(22125103); Shanghai Municipal Major Basic Research Project(22JC1401000); China Postdoctoral Science Foundation(2023M731094); China Postdoctoral Science Foundation(BX20230127)

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Abstract

Praeruptorin E expresses specific and diverse biological activities but with no synthetic report, which dramatically limits its medicinal research. Structural analysis reveals that there are four major challenges in the synthesis of this nature product: enantioselectivity, chemoselectivity, regioselectivity, and Z/E selectivity. Herein, the first asymmetric total synthesis of praeruptorin E was achieved through five/seven steps, utilizing commercially available 3-methyl-2-butenal and triethyl orthoformate as raw materials. Additionally, a eight-membered library of praeruptorin E analogs has also been established via this strategy, laying a solid foundation for its activity test and drug discovery.

Key words: praeruptorin E, enantioselectivity, chemoselectivity, regioselectivity, Z/E selectivity

Cite this article

Leiyang Bai, Bei Fu, Haiping Liu, Xiang Chun, Xuefeng Jiang. Total Synthesis of Praeruptorin E[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 1009-1020.

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Fig. & Tab. 9

References 17

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Entry	Conditions	Yield/%	ee/%
1	AD-mix-β (1.77 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	No reaction	—
2	AD-mix-β (1.77 equiv.), CH₃SO₂NH₂ (10 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	No reaction	—
3	AD-mix-β (1.77 equiv.), CH₃SO₂NH₂(1 equiv.), K₂OsO₂(OH)₄ (0.03 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	70	40
4	K₂OsO₂(OH)₄(0.02 equiv.), C₆FeK₃N₆ (3 equiv.), (DHQD)₂PYR (0.02 equiv.), K₂CO₃(3 equiv.), CH₃SO₂NH₂(1 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	90	40

Entry	Conditions	Yield/%	ee/%
1	AD-mix-β (1.77 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	No reaction	—
2	AD-mix-β (1.77 equiv.), CH₃SO₂NH₂ (10 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	No reaction	—
3	AD-mix-β (1.77 equiv.), CH₃SO₂NH₂(1 equiv.), K₂OsO₂(OH)₄ (0.03 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	70	40
4	K₂OsO₂(OH)₄(0.02 equiv.), C₆FeK₃N₆ (3 equiv.), (DHQD)₂PYR (0.02 equiv.), K₂CO₃(3 equiv.), CH₃SO₂NH₂(1 equiv.), ^tBuOH/H₂O (V∶V=1∶1), 0 ℃	90	40

Entry	(DHQD)_xY	Yield/%	ee/%
1	(DHQD)₂PHAL	90	40
2	(DHQD)₂AQN	90	43
3	(DHQD)PHN	93	77
4	(DHQD)₂PYR	95	83

Entry	(DHQD)_xY	Yield/%	ee/%
1	(DHQD)₂PHAL	90	40
2	(DHQD)₂AQN	90	43
3	(DHQD)PHN	93	77
4	(DHQD)₂PYR	95	83

Entry	4/equiv.	Conditions	Yield^a/%	Ratio of 3∶12∶13^b
1	1.5	Pyridine, DCM, r.t.	30	3∶3∶4
2	2.0	DCC, DMAP, DCM, r.t.	40	4∶3∶3
3	1.5	DCC, DMAP, DCM, r.t.	45	45∶25∶30
4	1.1	DCC, DMAP, DCM, 0 ℃	90	90∶1∶9^c
5	1.1	DCC, DMAP, DCM, 0 ℃	60	60∶35∶5

白花前胡素E的全合成研究

Total Synthesis of Praeruptorin E

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References 17

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Entry	Conditions	Product	Yield/%
1	DCC, DMAP, DCM, 0 ℃	1'	60
2	Pyridine, DCM, r.t.	1'	40
3	DPPA, Et₃N, DMF, r.t.	—	N.R.^a
4	T₃P, DCM, 45 ℃	—	N.R.^a
5	DMTMM, THF, 70 ℃	—	N.D.^b
6	EEDQ, DCM, 40 ℃	—	N.D.^b
7	PPh₃, DEAD, THF	—	N.D.^b
8	2,4,6-Trichlorobenzoyl chloride, Et₃N, toluene	1	5~10

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