盐酸(R)-沙丁胺醇的不对称合成

研究了一种化学不对称合成盐酸(R)-沙丁胺醇的方法. 以自制的手性龙脑基β-二酮铁络合物为催化剂催化起始原料3-乙酰氧基甲基-4-乙酰氧基苯乙烯(1)的不对称环氧化, 得到(R)-3-乙酰氧基甲基-4-乙酰氧基苯基环氧乙烷(2), 这一步的化学收率和光学收率都较高. 然后环氧化合物2与叔丁胺发生开环反应, 再与盐酸成盐即制得盐酸(R)-沙丁胺醇. 合成盐酸(R)-沙丁胺醇只需两步, 总收率为68%. 还考察了反应温度、催化剂种类、催化剂的量等因素对3-乙酰氧基甲基-4-乙酰氧基苯乙烯(1)的不对称环氧化的化学产率和光学收率的影响.     

(S)-和(R)-盐酸氟西汀的不对称合成

盐酸氟西汀是一种临床广泛使用的非三环类抗抑郁药, 本工作介绍了一种不对称合成(S)-和(R)-盐酸氟西汀的方法. 以自制的手性噁唑硼烷为催化剂, 将起始原料β-氯苯丙酮不对称催化氢化还原成(S)-或(R)-手性醇, 这一步的化学收率和光学收率都较高. 然后再经两步, (S)-和(R)-手性醇转化为(S)-和(R)-盐酸氟西汀. 整个工艺只需三步, 总收率为66.5%, 盐酸氟西汀对映体的ee值可达98.6%. 还考察了反应温度、溶剂、催化剂的量等因素对β-氯苯丙酮的不对称氢化还原的化学产率和光学收率的影响.     

L-脯氨酸对离子液体介质中的不对称Michael反应催化性能研究

研究了L-脯氨酸对离子液体介质中醛(酮)与β-硝基烯烃的不对称Michael加成反应的催化性能, 利用X射线单晶衍射对Michael产物结构进行了表征. 结果表明, 反应在遵循胺催化机理的同时, 烯胺是从Re面对β-硝基烯烃进行加成, 产物的优势结构为(1R,2S)的syn型. 脯氨酸在离子液体1-正己基-3-甲基咪唑氯盐中显示良好的催化性能, 室温反应3～5 h, 得到89%以上收率的Michael产物, 其ee值最高70%. 脯氨酸与离子液体形成的催化体系具有良好的重复使用性能, 可至少稳定地重复使用6次.     

ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯的制备

格氏试剂和N-叔丁氧羰基焦谷氨酸乙酯反应生成中间体ω-苯基-δ-氧代-(2S)-N-叔丁氧羰基氨基酸乙酯, 分别用对甲基苯磺酰肼和醋酸硼氢化钠结合的一锅法还原或Pd/C催化氢化还原中间体得到ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯.     

(S)-和(R)-普萘洛尔的不对称合成

普萘洛尔是一种临床上广泛使用的β受体阻断剂, 介绍了一种不对称合成(S)-和(R)-普萘洛尔的方法. 以手性Salen-Co^III催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯度的(S)-环氧氯丙烷和(R)-3-氯-1,2-丙二醇, 以(S)-环氧氯丙烷为手性原料先水解得(S)-3-氯-1,2-丙二醇, 其与1-萘酚反应得(S)-3-(1-萘基)-丙烷-1,2-二醇, 再与氯化亚砜反应得环状亚硫酸酯, 最后和异丙胺作用得(S)-普萘洛尔, 总收率80.9%, 光学纯度大于99%; 而同样以(S)-环氧氯丙烷为手性原料直接与1-萘酚反应得(2R)-3-(1-萘氧基)-1,2-环氧丙烷, 再与异丙胺作用得(R)-普萘洛尔, 总收率74.5%, 光学纯度大于99%.     

(S)-N-Boc-α-氨基庚(辛)二酸单酯和双酯的制备

以(S)-N-Boc焦谷氨酸乙酯为原料, 经DIBAL-H还原得到半缩醛, 然后经Wittig反应得到相应的烯烃, 最后氢化制得(S)-N-Boc-α-氨基庚二酸二(单)酯, 总收率为85.1%(二酯)和86.1%(单酯). 另外, 以(S)-N-Boc-哌啶-2-甲酸为原料经酯化和氧化得内酰胺, 然后经还原、Wittig反应、氢化得到(S)-N-Boc-α-氨基辛二酸二(单)酯, 总收率为72.5%(二酯)和72.4%(单酯). 产品用¹H NMR, MS表征.     

利用甾体皂甙元氧化降解废弃物(R)-4-甲基-δ-戊内酯合成松叶蜂主要性信息素(2S,3S,7S)-3,7-二甲基-2-十五醇乙酸酯和丙酸酯

首次利用甾体皂甙元氧化降解废弃物(R)-4-甲基-δ-戊内酯合成了松叶蜂性信息素(2S,3S,7S)-3,7-二甲基-2-十五醇乙酸酯(2)和丙酸酯(3). 甾体皂甙元氧化降解废弃物(R)-4-甲基-δ-戊内酯首先被转化成为性质稳定易保存的(R)-5-溴-4-甲基戊酸甲酯(5), 化合物5经过偶联、还原、溴代、环氧加成开环和酰化反应给出目标分子. 本研究结果不仅为松叶蜂性信息素化合物2和3提供了一个简洁有效的合成方法, 同时也丰富了资源化学(即基于资源性化合物合理利用的有机合成化学)的内涵.     

手性β-氨基醇的合成及其催化二乙基锌与醛的不对称加成反应

以烯烃为原料通过Sharpless不对称双羟化等多步反应合成7种手性β-氨基醇, 并将该类化合物用于催化二乙基锌和醛的不对称加成反应. 分别考察了影响对映选择性的催化剂结构、催化剂用量、溶剂、反应温度等各种因素. 当催化剂用量为5%、甲苯溶剂、在－10 ℃下、以(1S,2R)-(＋)-2-氨基-1,2-二苯基乙醇(1b)作催化剂时, 所得仲醇的对映体过量最高为85% ee, 产率高达100%.     

利用工业废弃物中获得的(R)-5-甲基-δ-戊酸内酯为原料合成(2R,6R)-2,6,10-三甲基十一醇

(2R,6R)-2,6,10-三甲基十一醇(1)是维生素E、维生素K和植醇的基本结构单元. 利用从甾体皂甙元氧化降解产生的工业废弃物中所获得的手性化合物(R)-5-甲基-δ-戊酸内酯(6), 先将其转化成为化学性质稳定的(4R)-甲基-5-甲氧甲氧基戊酸甲酯(7), 再经十二步反应, 以14.1%的总收率合成得到了目标化合物(2R,6R)-2,6,10-三甲基十一醇(1).     

α-亚胺酮的不对称转移氢化合成(R)-沙丁胺醇

用手性(S,S)-Ru-TsDPEN催化剂不对称转移氢化α-亚胺酮化合物5-[(1,1-二甲基乙基)亚胺基]乙酰基-2-羟基苯甲酸甲酯(2)得光学纯β-氨基芳基乙醇类化合物(R)-5-[2-[(1,1-二甲基乙基)氨基]-1-羟乙基]-2-羟基苯甲酸甲酯(3), 再经一步还原反应即得(R)-(－)-沙丁胺醇. 对反应关键一步α-亚胺酮的不对称转移氢化反应条件进行了研究.     

一种新的测定寡糖链中糖体亚谱的NMR方法

报道一种新的测定寡糖链糖体亚谱的NMR方法, 称为MMDY混合脉冲梯度选择一维HOHAHA法. 本方法采用MMDY混合脉冲与双梯度自旋回波脉冲相结合, 为解决高度重叠的¹H NMR谱图分析困难提供了有力手段. 本方法的主要特点是: 采用双梯度自旋回波脉冲进行选择激发, 与差谱为基础的选择激发方法相比不但可节省测定时间, 而且谱图干净, 没有差谱伪峰; MMDY混合脉冲的磁化接力相干转移非常有效, 远程磁化转移信号的灵敏度高, 对于偶合常数大约为1 Hz的微弱偶合自旋体系, 如阿拉伯糖和鼠李糖, 也能够得到完整的亚谱; 梯度脉冲只是用于相干路径选择, 灵敏度比较高, 并且纯吸收形的高质量亚谱不经过复杂的Z-滤波步骤就可以快速得到, 因此比较适用于常规样品分析. 以苷类化合物为例讨论本方法的特点以及在谱峰高度的寡糖结构测定中的应用.     

^1H NMR选择检测新技术用于新三萜皂苷的结构研究

从中药川续断根部的乙醇提取物中分得1个新的三萜皂苷,经过测定,其结构为:3-O-α-L-吡喃鼠李糖(1--3)-β-D-吡喃葡萄糖(1--3)-β-L-吡喃鼠李糖(1--2)-β-L-吡喃阿拉伯糖-常春藤苷元(1).研究表明,采用一维SEMDY和三照射NOE差谱NMR新技术相结合能以"拼凑"方式,测定糖链结构.方法简便、快速、测定结果可靠,重叠的信号可以指认,并且对样品不必进行化学降解或衍生化.本方法也可以用于其他类型的寡糖结构测定。     

HMBC-RELAY: a combined technique for the differentiation of simultaneously detected 2J(C,H) and (n)J(C,H) connectivities

We present a new pulse sequence that detects simultaneously (n)J(C,H) and 2J(C,H) connectivities. The corresponding coherences are created along independent pathways and therefore can be separated into two different subspectra. One spectrum is to show all (n)J(C,H) connectivities and the other is to show exclusively 2J(C,H) connectivities. In contrast to the previously published 2J/(n)J experiment, this sequence detects the 2J(C,H) connectivities via a C,H,H-RELAY pathway leading to an intensification of the 2J(C,H) signals. Strictly, the 2J(C,H) spectrum does not show 2J(C,H) but 3J(H,H) coupling interactions within 13CH(k)-12CH(l) fragments. Therefore, 2J(C,H) signals can appear even if the corresponding 2J(C,H) coupling constant is zero.     

2D Selective‐TOCSY‐DQFCOSY Experiment for Identification of Individual Sugar Components in Oligosaccharides

In this paper, we describe an improved 2D selective‐TOCSY‐COSY experiment for the unambiguous assignment of an individual sugar component in oligosaccharides. We used a DQFCOSY with a pulsed‐field gradient instead of a conventional COSY in this improved experiment. The network of proton signals for a selected sugar in an oligosaccharide is observed as the diagonal peaks in the 2D spectrum by use of the first TOCSY period, and the correlation signals between J‐coupled neighboring protons are clearly observed as the cross peak, including the signals observed close to the diagonal peaks by the second DQFCOSY development. Even when the signals do not appear in a well‐separated form of a 1D spectrum, unambiguous sequential assignment of the proton signals of individual sugar components in an oligosaccharide is achieved by this method.     

二维接力HOHAHA和—维多重接力COSY研究苷类化合物的结构

苷类化合物的糖体质子大多相互有自旋偶合作用,构成一个复杂的自旋系统。糖体端基质子(H-1)NMR 信号大多为双峰,出现在较     

A new selective population transfer experiment using a double pulsed field gradient spin-echo

A new pulse sequence is proposed for the determination of scalar coupling correlation in small- and medium-sized organic compounds. The method uses a combination of the double pulsed field gradient spin-echo (DPFGSE) and the selective population transfer (SPT) techniques and is shown to be useful in the analysis of complex spectra with many overlapped signals. The usefulness of this method in the structural elucidation of natural substances is demonstrated using strychnine and digitoxin as examples.     

Multiple quantum correlated spectroscopy revamped by asymmetric z-gradient echo detection signal intensity as a function of the read pulse flip angle as verified by heteronuclear 1H/31P experiments

Heteronuclear multiple quantum (n=+/-0 and n=+/-2) correlated spectroscopy revamped by asymmetric z-gradient echo detection (CRAZED) experiments were performed on the spins 31P and 1H in a H3PO4 solution in order to determine the optimum flip angle for the read pulse. It has been shown that for the negative quantum signals, the maximum signals appear at beta=0, and for the positive quantum signals, the maximum signals appear at beta=pi. The CRAZED signals were compared to the single quantum signals in two-pulse two-gradient experiments. It is found that the CRAZED signals can also be distinguished into gradient echoes and spin echoes. The gradient-echo-type CRAZED signal requires beta=0 and the spin-echo-type CRAZED signal requires beta=pi for maximum echo intensities, in the same way as in single quantum experiments.     

Spectroscopic separation of 13C NMR spectra of complex isomeric mixtures by the CSSF‐TOCSY‐INEPT experiment

Isomeric mixtures from synthetic or natural origins can pose fundamental challenges for their chromatographic separation and spectroscopic identification. A novel 1D selective NMR experiment, chemical shift selective filter (CSSF)‐TOCSY‐INEPT, is presented that allows the extraction of ¹³C NMR subspectra of discrete isomers in complex mixtures without physical separation. This is achieved via CSS excitation of proton signals in the ¹H NMR mixture spectrum, propagation of the selectivity by polarization transfer within coupled ¹H spins, and subsequent relaying of the magnetization from ¹H to ¹³C by direct INEPT transfer to generate ¹³C NMR subspectra. Simple consolidation of the subspectra yields ¹³C NMR spectra for individual isomers. Alternatively, CSSF‐INEPT with heteronuclear long‐range transfer can correlate the isolated networks of coupled spins and therefore facilitate the reconstruction of the ¹³C NMR spectra for isomers containing multiple spin systems. A proof‐of‐principle validation of the CSSF‐TOCSY‐INEPT experiment is demonstrated on three mixtures with different spectral and structural complexities. The results show that CSSF‐TOCSY‐INEPT is a versatile, powerful tool for deconvoluting isomeric mixtures within the NMR tube with unprecedented resolution and offers unique, unambiguous spectral information for structure elucidation. Copyright © 2014 John Wiley & Sons, Ltd.     

Editing of H2BC NMR spectra

New versions of the H2BC pulse sequence (Nyberg NT, Duus JØ, Sørensen OW. J. Am. Chem. Soc. 2005; 127: 6154) that edit into two subspectra according to the number of protons attached to ¹³C nuclei being odd or even are introduced. These sequences can be useful for resolving spectral overlap, which is demonstrated on the molecule prednisolone [(11 β)‐11,17,21‐trihydroxypregna‐1,4‐diene‐3,20‐dione] Copyright © 2005 John Wiley & Sons, Ltd.     

Simultaneous measurement of N?H and Cα?Hα coupling constants in proteins

We present a pulse sequence for the simultaneous measurement of N? H and Cα? Hα couplings in double‐labeled proteins from 2D spectra. The proposed sequence, a modification of the HN(CO)CA experiment, combines the J‐modulation method and the IPAP scheme. The couplings can be readily retrieved from a series of 2D ¹⁵N? ¹H correlation spectra, differing in the time point at which a ¹H 180° pulse is applied. This induces an intensity modulation of the ¹⁵N? ¹H correlation peaks with the Cα? Hα coupling. The Cα? Hα coupling is then obtained by fitting the observed intensities to the modulation equation. The N? H coupling is measured in each member of the set from peak‐to‐peak separations in the IPAP subspectra. The pulse sequence is experimentally verified with a sample of ¹⁵N/¹³C‐enriched ubiquitin. Copyright © 2009 John Wiley & Sons, Ltd.