基于杂环的不对称插烯Mannich反应及其在生物碱合成中的应用进展

基于杂环(α,β/β,γ-不饱和γ-内酯,α,β-不饱和γ-内酰胺)的插烯Mannich反应在构建新C—C键的同时形成含邻氨基醇片段的α,β-不饱和γ-内酯和含邻二胺片段的α,β-不饱和γ-内酰胺结构单元,是构建含氧、含氮杂环及合成生物碱的重要合成砌块,具有广泛的应用价值.对2011年以来基于杂环的不对称插烯Mannich反应研究进展进行综述,涵盖手性辅助基诱导的插烯Mannich反应、金属-手性配体络合物和有机小分子催化的不对称插烯Mannich反应及其在复杂生物碱合成中的应用.文中也对相关方法的局限进行了分析.国家重点研发计划(No.2017YFA0207302);;国家自然科学基金(Nos.21332007,21472153);;教育部长江学者和创新团队发展计划;;中央高校基本科研业务费专项资金(Nos.20720170092,20720180024);;福建省自然科学基金(No.2017J01021)资助项目~

Studies on the Interactions between Bioactive Peroxovanadium Complexes Bearing Organic Ligands and Histidine

在合成和表征了 4种具有较强生物活性双过氧钒配合物K3 [VO(O2 ) 2 (ox) ]·2H2 O ,Na[VO(O2 ) 2 (bipy) ]·5H2 O ,K[VO(O2 ) 2 (phen) ]·3H2 O和K2 [VO(O2 ) 2 (pic) ]·2H2 O [分别缩写为pV(ox) ,pV(bipy) ,pV(phen)和pV(pic) ,其中ox为草酸根 ,bipy为 2 ,2′ 联吡啶 ,phen为邻菲咯啉 ,pic为 2 羧酸吡啶负离子 ]的基础上 ,利用多种NMR技术和电喷雾质谱 (ESI MS)研究了这 4种含有机配体双过氧钒配合物与组氨酸 (His)在溶液中的相互作用以及反应物浓度、时间、pH等对相互作用体系的影响 .51VNMR跟踪监测的结果表明 :双过氧钒配合物pV(ox)和pV(pic)与His在中性水溶液中存在强配位相互作用 ,而pV(bipy)和pV(phen)与His在中性水溶液中无明显作用 .我们还利用谱学方法确定了pV(ox)和His相互作用后所生成产物是pV(ox)分别与His咪唑基上的 3 N和 1 N配位的一对异构体. 　In order to explore the structure2activity relationship and molecular mechanism of the specific recognition between peroxovanadium (pV) complexes bearing organic ligands and the target enzymes of tyrosine phosphatase , several NMR techniques and ESI2MS were used to study the interactions of four pV complexes {pV(ox) , pV ( bipy) , pV (phen) and pV (pic) , where pV = [VO (O2 ) 2L ] n - , in which L = oxalic acid dianion (ox) , bipyridine (bipy) , 1 ,102phenanthroline (phen) , and pyridine222carboxylic acid (pic) } towards histidine. Strong coordination interactions between imidazole of histidine and vanadium of pV(ox) or pV(pic) were observed in neutral solution , while there are not obvious interactions between histidine and pV(bipy) or pV(phen) . All 13C and 1H NMR signals of 1∶1 stoichiometric mixture of pV(ox) and histidine were assigned. Spectroscopic studies demonstrated that new complexes in the mixture of pV(ox) and histidine are a pair of isomers in which the vanadium in pV(ox) binding to the 32N and 12N of the imidazole ring. Moreover , the results of effective factors on the interaction system indicated that the new isomers were stable under the condition of physiological pH and the structure2activity relationship of these pV complexes may be relevant to their specific recognition towards histidine residues in tyrosine phosphatase.国家自然科学基金 (Nos.2 0 172 0 42 ,2 9832 0 2 0 )资助项

Towards Reaction Control: cis-Diastereoselective Reductive Dehydroxylation of 5-Alkyl-4-Benzyloxy-5-Hydroxy-2-Pyrrolidinones

通讯作者地址: Huang, PQA chemo-, regio-, and stereoselectively controlled reaction is highly desirable, yet challenging in organic synthesis. Diversely substituted cis and trans isomers of 2-alkyl-3-pyrrolidinols, 5-alkyl-4-hydroxy-2-pyrrolidinones, beta-hydroxy-gamma-amino acids, and their higher homologues are key structural units found in numerous drugs, drug candidates, and bioactive natural products. Previously, we established a flexible approach to trans-5-alkyl-4-benzyloxy-2-pyrrolidinones 14 and trans-6-alkyl-5-benzyloxy-2-piperidinones 15. Herein, we report a direct, flexible, moisture insensitive, and highly diastereoselective approach to the corresponding cis diastereomers 16. This stereocontrolled method is based on the MsOH-mediated (Ms=methane sulfonyl) reductive dehydroxylation of hemiaminal 12 with NaBH(OAc)(3). cis-5-Alkyl-4-benzyloxy-2-pyrrolidinones 16 are useful building blocks for the syntheses of natural products such as (+)-preussin (4) and streptopyrrolidine (5) as well as (3S,4S)-gamma-alkyl-beta-hydroxy-gamma-amino acids (6).National Basic Research Program (973 Program) of China 2010CB833200 NSF of China 20832005 21072160 Natural Science Foundation of Fujian Province 2011J0105

~(51)V NMR监测[VS_4Cu_n](n≤6)簇合物自兜反应过程

采用　51VNMR监测在核磁管内模拟 (NH4 ) 3VS4 /Et4 NBr/CuBr/PPh3体系在CH2 Cl2 中的反应过程 ,研究了反应条件如反应物不同配比对生成各种 [VS4 Cun](n≤ 6)簇合物的影响 ,提供了该反应体系在CH2 Cl2 溶液中成簇过程的一些信息 .该方法不仅可用来研究反应机理 ,而且可用于指导一些条件难以确定 (溶剂、温度、酸碱度等 )的簇合物如低核数及更高核数V Cu S簇合物的合

Rh/SiO_2催化剂上甲烷部分氧化制合成气的核磁共振研究

利用1HMASNMR技术 ,在甲烷部分氧化 (POM)制合成气反应条件下研究了Rh/SiO2 催化剂上氢与金属的相互作用及反应机理 .结果发现 ,氢气在Rh/SiO2 上解离吸附后可能有四种存在形式 :化学位移为δ =- 10 0～ - 12 0的可逆 (αM)和不可逆 (αI)吸附氢物种 ,δ =0～ - 10 0的“氢云”或“氢雾”形式的氢物种和δ =3 0的溢流氢物种 .溢流氢物种是由可逆吸附的氢物种和“氢云”或“氢雾”状态的氢物种溢流到SiO2 上并弱吸附在桥式氧 (Si-O-Si)附近而形成的 .溢流氢物种活化晶格氧 ,形成一种POM反应的活性氧物种OH-.活性氧物种OH-反溢流到Rh上 ,并与CH4解离吸附在Rh上的CHx 物种反应生成含氧中间物种CHxO .CHxO物种的化学位移为 5～ 7.O2 参与CHxO物种的进一步氧化 ,或补充溢流氢夺取桥式氧后形成的缺陷位上的晶格氧 ,在高温 (973K)反应条件下 ,O2 可能优先补充缺陷位上的晶格氧 ,使CHx 的氧化按表面反应机理进行

Rh/SiO_2催化剂上甲烷部分氧化制合成气的核磁共振研究

利用1HMASNMR技术 ,在甲烷部分氧化 (POM)制合成气反应条件下研究了Rh/SiO2 催化剂上氢与金属的相互作用及反应机理 .结果发现 ,氢气在Rh/SiO2 上解离吸附后可能有四种存在形式 :化学位移为δ =- 10 0～ - 12 0的可逆 (αM)和不可逆 (αI)吸附氢物种 ,δ =0～ - 10 0的“氢云”或“氢雾”形式的氢物种和δ =3 0的溢流氢物种 .溢流氢物种是由可逆吸附的氢物种和“氢云”或“氢雾”状态的氢物种溢流到SiO2 上并弱吸附在桥式氧 (Si-O-Si)附近而形成的 .溢流氢物种活化晶格氧 ,形成一种POM反应的活性氧物种OH-.活性氧物种OH-反溢流到Rh上 ,并与CH4解离吸附在Rh上的CHx 物种反应生成含氧中间物种CHxO .CHxO物种的化学位移为 5～ 7.O2 参与CHxO物种的进一步氧化 ,或补充溢流氢夺取桥式氧后形成的缺陷位上的晶格氧 ,在高温 (973K)反应条件下 ,O2 可能优先补充缺陷位上的晶格氧 ,使CHx 的氧化按表面反应机理进行

Studies on the interactions between bioactive peroxovanadium complexes bearing organic ligands and histidine

In order to explore the structure-activity relationship and molecular mechanism of the specific recognition between peroxovanadium. (pV) complexes bearing organic ligands and the target enzymes of tyrosine phosphatase, several NMR techniques and ESI-MS were used to study the interactions of four pV complexes {pV(ox), pV(bipy), pV(phen) and pV(pic), where pV=[VO(O-2)(2)L](n-), in which L=oxalic acid dianion (ox), bipyridine (bipy), 1, 10-phenanthroline (phen), and pyridine-2-carboxylic acid (pic)} towards histidine, Strong coordination interactions between imidazole of histidine and vanadium of pV(ox) or pV(pic) were observed in neutral solution, while there are not obvious interactions between histidine and pV(bipy) or pV (phen). All C-13 and H-1 NMR signals of 1:1 stoichiometric mixture of pV (ox) and histidine were assigned. Spectroscopic studies demonstrated that new complexes in the mixture of pV (ox) and histidine are a pair of isomers in which the vanadium in pV(ox) binding to the 3-N and 1-N of the imidazole ring. Moreover, the results of effective factors on the interaction system indicated that the new isomers were stable under the condition of physiological pH and the structure-activity relationship of these pV complexes may be relevant to their specific recognition towards histidine residues in tyrosine phosphatase

异三核过渡金属配合物〔Fe2Ⅲ MⅡO（OOCC2H5）6L3〕（M=Co,Ni,Mn;L=C5 H5N,H2O）溶液行为的NMR和UV谱表征

A series of new heterotrinuclear transition-metal complexes [(Fe2MO)-M-I-O-I(OOCC2H5)(6)L-3] (M = Co, Ni, Mn; L = C5H5N, H2O) were synthesized and characterized. Their structures and dynamics in different solutions and temperatures were investigated by NMR and UV. Assignments of the H-1 NMR spectra were made on the basis of relative intensities, broadening, substitution with appropriate ligands and spin-lattice relaxation. Experimental results shows that there is antiferromagnetic exchange interaction among the three metal ions within M3O core. It is found that these complexes in DMSO, CD3CN, CDl(3) and CD3COCD3 solvents are stable at room temperature and their structures in solution are the same as their crystal ones. However, the complexes decomposed into carboxylic acid, pyridin and metal ions in water. The results may be helpful in guiding synthesis of similar complexes

酰亚胺α-烷基化反应及其在γ-取代-β-羟基-γ-氨基酸类化合物的不对称合成中的应用

学位：理学硕士院系专业：化学化工学院化学系_有机化学学号：1993440

2D NMR Study on Solution Structure of Natural Product 3′-Methoxy Puerarin

【中文文摘】3′ 甲氧基葛根素是从常用中药野生葛根中分离提取出来的一种具有很强生物活性的异黄酮类化合物.该化合物含季碳较多,有些13CNMR的谱峰不易归属.本文利用包括氢检测异核多量子相干谱(HMQC)和氢检测远程异核多量子相干谱(HMBC)等多种二维核磁共振技术对该天然产物的13C和1HNMR谱峰进行了全归属.这些工作有助于利用二维核磁共振技术研究和确定含季碳较多的异黄酮类新化合物的结构和利用扩散相关的核磁共振新技术研究葛根的生理活性成份与靶分子相互作用. 【英文文摘】An active isoflavone compound 3′methoxy puerarin was isolated from puerarin lobate (willd). Several twodimensional NMR new techniques, including 1Hdetected heteronuclear multiplequantum coherence and 1Hdetected multiplebond heteronuclear multiplequantum coherence, were employed to completely assign all the protons and carbons of the compound. This work solves the assignments of uncertain C3 and C1′ NMR signals in the previous literature and will be helpful to study the structures of this kind of new isoflavone compounds by 2D NMR spectroscopy and bioactive compounds in puerarin lobate directly by diffusion2chemical shift 2D NMR.国家自然科学基金(20172042);; 国家中医药管理局与福建省卫生厅基金(2000 J P 40)资助项