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 Acetic Acid Based on Microwave Assisted Wittig-Michael Tandem Reaction

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(Ph3P CHCOOEt)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.

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 andβ-stereoselectively in CH3 CN at 115 ℃ with a yield up to 91% within 10 min, and theα-stereomer could easily converted to the thermodynamically more sta-ble β-stereomer during workup in basic condition. The calculation results of quantum chemistry show thatβ-isomer 4b is higher thanα-isomer 4a in thermodynamic stability. The structures of the compounds were iden-tified by spectral analyses of 1 H NMR, 13 C NMR and HRMS.