微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物

doi:10.7503/cjcu20131054

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (5): 959.doi: 10.7503/cjcu20131054

微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物

马东来¹, 李小六¹(), 郝乐¹, 张平竹¹, 陈华¹, 赵影²

1. 河北大学化学与环境科学学院, 河北省化学生物学重点实验室, 保定 071002
2. 河北农业大学理学院, 保定 071001

收稿日期:2013-10-29 出版日期:2014-05-10 发布日期:2014-04-12
作者简介:联系人简介: 李小六, 男, 博士, 教授, 主要从事糖类衍生物的设计合成及生物活性研究. E-mail:lixl@hbu.cn
基金资助:
国家自然科学基金(批准号: 21172051, 21372060)、河北省重点基础研究项目(批准号: 12966417D)、河北省自然科学基金(批准号: Y2011119, ZH2011110)和河北省自然科学基金石药集团医药联合基金(批准号: B2011201169, B2012201113)资助

Stereospecific Synthesis of ω-Amino-β-D-furanoribosyl cetic Acid Based on Microwave Assisted ittig-Michael Tandem Reaction^†

MA Donglai¹, LI Xiaoliu^1,^*(), HAO Le¹, ZHANG Pingzhu¹, CHEN Hua¹, ZHAO Ying²

1. Key Laboratory of Chemical Biology of Hebei Province, School of Chemistry and nvironmental Science, Hebei University, Baoding 071002, China
2. College of Science, Agricultural University of Hebei, Baoding 071001, China

Received:2013-10-29 Online:2014-05-10 Published:2014-04-12
Contact: LI Xiaoliu E-mail:lixl@hbu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21172051, 21372060), the Key Basic Research Foundation of Hebei Province, China(No.12966417D) and the Natural Science Foundation of Hebei Province, China(Nos.Y2011119, ZH2011110) and the Medicinal Joint Founds of the Natural Science Foundation of Hebei Province and Shijiazhuang Pharmaceutical Group Foundation of China(Nos.B2011201169, B2012201113)

摘要/Abstract

摘要：

以D-核糖为原料, 在微波促进下, 利用2,3-O-异丙叉基-D-核糖2与叶立德3(Ph₃PCHCOOEt) 的Wittig反应和Michael加成, 立体专一性地合成了β-D-呋喃核糖酸酯类化合物, 再经叠氮化及还原反应, 得到ω-氨基-β-D-呋喃核糖酸衍生物. 在微波辐射下, 该Wittig-Michael串级反应的效率得到显著提高, 反应时间由12 h缩短为10 min, 收率达到91%. 反应具有非常好的β-立体选择性, 在碱性条件下处理后, α-异构体可转变成热力学稳定的β-异构体, 从而得到单一的β-异构体. 计算结果表明, β-异构体4b比α-异构体4a具有更高的热力学稳定性.

关键词: 氨基呋喃核糖酸酯, 微波促进反应, Wittig-Michael串级反应

Abstract:

An efficient and stereoselective method for synthesizing ω-amino-β-D-furanoribosylactic ester was established based on the microwave assisted Wittig-Michael tandem reaction of acetone protection of D-ribose(2) and Ylide 3(Ph₃P═CHCOOEt), and followed by ω-azidation and reduction. The microwave assisted Wittig-Michael addition reaction was carried out effectively and β-stereoselectively in CH₃CN at 115 ℃ with a yield up to 91% within 10 min, and the α-stereomer could easily converted to the thermodynamically more stable β-stereomer during workup in basic condition. The calculation results of quantum chemistry show that β-isomer 4b is higher than α-isomer 4a in thermodynamic stability. The structures of the compounds were identified by spectral analyses of ¹H NMR, ¹³C NMR and HRMS.

Key words: Amino furanoribosyl acid ester, Microwave assisted reaction, Wittig-Michael tandem reaction

中图分类号:

O629.11

TrendMD:

马东来, 李小六, 郝乐, 张平竹, 陈华, 赵影. 微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物. 高等学校化学学报, 2014, 35(5): 959.

MA Donglai, LI Xiaoliu, HAO Le, ZHANG Pingzhu, CHEN Hua, ZHAO Ying. Stereospecific Synthesis of ω-Amino-β-D-furanoribosyl cetic Acid Based on Microwave Assisted ittig-Michael Tandem Reaction^†. Chem. J. Chinese Universities, 2014, 35(5): 959.

图/表 7

Fig.1 Structures of some sugar amino acid derivatives

Ethyl 2-C-(5'-deoxy-5'-amino-D-β-furanoribosyl)-acetate(1)^Reagents and conditions: (1) a. CH3CN, MW, 115 ℃; b. MeONa, MeOH; (2) MsCl, pyridine, 0 ℃; (3) NaN3, DMF, 100 ℃; (4) 12% HCl, EtOH, 10% Pd/C, H2.

Scheme 2 Process of the Wittig-Michael reaction

Table 1 Microwave assisted Wittig-Michael reaction of sugar(2) and Ylide(3)a

Entry	Solvent	Temperature/℃	t/min	Yield(%)	Entry	Solvent	Temperature/℃	t/min	Yield(%)
1	Toluene	135	10	87.5	7	CH₃CN	115	10	91
2	Xylene	160	10	85	8	CH₃CN	115	5	64
3	CH₃OH	100	10		9	CH₃CN	115	15	91
4	CH₃CN	81	10		10	CH₃CN	115	20	89
5	CH₃CN	100	10	60	11	CH₃CN	120	10	81.2
6	CH₃CN	110	10	85	12^b	CH₃CN	Reflux	720	80.5

Scheme 1 Conversion of compound 4a(α-isomer) to compound 4b(β-isomer) under basic condition

Fig.2 Optimized conformations of the isomers of compound 4

Table 2 Energy of the isomers of 4a and 4b*

Isomer	E_total/ eV	E_ele/ eV	E_rep/ eV	10³⁰μ/(C·m)	ΔE_LUMO-HOMO/(kJ·mol^-1)
4a	-22911.27	-56765.82	33854.55	12.55	676.91
4b	-22911.35	-55828.84	32917.49	5.64	701.61

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微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物

Stereospecific Synthesis of ω-Amino-β-D-furanoribosyl cetic Acid Based on Microwave Assisted ittig-Michael Tandem Reaction^†

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