摘要：

五配位磷化合物作为中间体或过渡态在生物学过程中被广泛的提出.本论文以氨基酸为原料合成并分离出 16 个单一绝对构型的双氨基酸五配位氢膦烷,通过高效液相色谱 (HPLC),核磁共振波谱 (NMR),X-射线单晶衍射技术,圆二色光谱 (CD),电喷雾质谱 (ESI-MS) 以及量子化学理论计算等分析手段对它们的立体结构进行了系统的研究. 本论文通过 L-型氨基酸与 PCl3 反应可以获得一对双氨基酸五配位氢膦烷的非对映异构体,与之类似,D-型氨基酸与 PCl3 反应可以获得另外一对双氨基酸五配位氢膦烷的非对映异构体.这些非对映异构体都可以利用非手性 HPLC 进行有效的分离 (纯度大于 99.5 %).固体 CD 光谱证明它们双双成对映异构体的关系,在非手性 HPLC 中有相同的保留时间及相似的波谱数据. 1H-1H COSY 实验发现其中一类双氨基酸五配位氢膦烷中氨基酸侧链 α-CH 与 PH 之间具有远程相关作用,4JH-C-N-P-H 为 2.4 Hz.量子化学理论计算表明在双氨基酸五配位氢膦烷的非对映异构体之间,P-H 键与氨基酸侧链 α-位碳原子的 C-H 键空间伸展方向不同,进而造成了 1H-1H COSY 信号的差异,4JH-C-N-P-H 分别为 2.5 或 0.5 Hz. 31P NMR 和 1H NMR 跟踪测试表明该系列化合物各单一绝对构型在中性有机溶剂 DMSO-d6 或 CDCl3 中,室温条件下,40 天内可以稳定不变.高纯度和较好的稳定性为绝对构型研究结论的可靠性和有效性奠定了很好的基础. X-射线单晶衍射技术对获得晶体结构的 8 个双氨基酸五配位氢膦烷的结构进行解析,确定该系列化合物中心磷原子属于三角双锥构型,H 原子和两个 N 原子在平伏键上,两个 O 原子在直立键上.在此基础上,借鉴配位化合物的命名规则,对其绝对构型进行命名,并通过固体 CD 光谱以及 1H NMR 对所有化合物的绝对构型进行关联. 本论文还系统的对 1JP-X (X = H, N) 进行了研究,实验测试表明:1JP-H 耦合常数的数值在四配位磷化合物中约为 700 Hz 小于在双氨基酸五配位氢膦烷中约为 800 Hz 的数值,而 1JP-N 耦合常数的数值在四配位磷化合物中约为 41 Hz 却大于在双氨基酸五配位氢膦烷中约为 32 Hz 的数值.利用量子化学理论计算,通过DFT/B3LYP/6-31+G(d,p) 对化合物的几何结构进行优化,再用 DFT/B3LYP/IGLO III 对其进行耦合常数的计算获得了与实验测试相同的结论,研究表明在双氨基酸五配位氢膦烷中,P-N 键具有双键的性质,从而降低了化学键中 s 轨道的比例,进而降低了相应的 1JP-N 耦合常数数值. 对双氨基酸五配位氢膦烷固体 CD 和溶液CD 的测试,以及对双缬(亮)氨酸五配位氢膦烷的 CD 光谱进行理论计算研究,确定了氨基酸侧链为饱和脂肪链的双氨基酸五配位氢膦烷的 CD 信号受到中心手性磷原子与氨基酸侧链 α-位手性碳原子的共同影响.由于在不同构型中两类手性原子对 CD 光谱的贡献不同,所以在非对映异构体之间 CD 光谱的最大吸收峰位置和吸收强度都有明显的差异. 最后,对双氨基酸五配位氢膦烷进行电喷雾多级质谱裂解规律研究发现,单纯的通过多级质谱裂解无法区分化合物的手性.在正离子模式下 ([M+H]+ 或 [M+Na]+),氨基酸侧链对相应的亚胺离子具有明显的稳定作用,伴随着氨基酸侧链变大 (特别是苯环基团存在时),亚胺离子的稳定性明显增强并影响多级质谱的裂解规律.在负离子模式下 ([M-H]-),对于双苯甘氨酸五配位氢膦烷因为苯环直接连接在化合物的螺环上,从而使得苯环在稳定该类化合物的负离子碎片上具有重要的作用,并表现出不同的裂解方式. 本论文充分发挥各种立体化学研究方法的优势,从多角度对手性双氨基酸五配位氢膦烷的结构进行探讨,并运用量子化学理论计算的方法对实验测试获得的数据进行合理的解释.Pentacoordinate phosphorus compounds as intermediates or transition state species are proposed in numerous biological processes. In this thesis, sixteen isomers of chiral bisamino acyl pentacoordinate spirophosphoranes derived from L- or D-amino acids were synthesized and separated, respectively. To investigate the stereochemistry of chiral bisamino acyl pentacoordinate spirophosphoranes systematically, these isomers were characterised by high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), single crystal X-ray diffraction, circular dichroism (CD), electrospray ionization mass spectrometry (ESI-MS) and the theoretical calculation of quantum chemistry. First of all, two sets of diastereoisomers of chiral bisamino acyl pentacoordinate spirophosphoranes derived from the reactions of L- or D-amino acids and PCl3. These diastereoisomers could be separated by achiral HPLC with the purity of 99.5 %. The solid-state CD spectra of enantiomers displayed virtually mirror images of each other, and showed the same retention times of achiral HPLC and similar NMR spectra, respectively. The 1H-1H COSY spectra of these compounds identified an interaction between the P-H proton and the α-hydrogen of amino acids, thus establishing unusual coupling through four bonds for these species with 4JH-C-N-P-H 2.4 Hz. This phenomenon was confirmed by the theoretical calculation of quantum chemistry. For diastereoisomers, the difference of the extensional orientation of P-H and C-H bond, which result in the difference of the 1H-1H COSY and the coupling of 4JH-C-N-P-H was 2.5 or 0.5 Hz Potential epimerization of these isomers were monitored by 31P and 1H NMR at rt using DMSO-d6 or CDCl3 as solvents to investigated the stability of these bisamino acyl pentacoordinate spirophosphoranes. No epimerization was observed over a period of forty days. The high enantiopurity and good configurational stability of these isomers is essential for the following stereochemistry study. The absolute configurations of these chiral bisamino acyl pentacoordinate spirophosphoranes were proven when eight crystal structures were characterized by single crystal X-ray diffraction analysis. These compounds arranged in a distorted TBP geometry. Two nitrogen atoms and a hydrogen atom form an equator plane and two oxygen atoms are in apical positions. Base on these data, we adopted the nomenclature system for coordination

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