双环氮杂锡氧烷配合物反应性质研究 5: 烷基化反应

首次讨论了双环氮杂锡氧烷配合物与卤代烷的烷基化反应,合成了5种新的双环氮杂锡氧烷配合物,并利用元素分析,IR,^1HNMR,^1^1^9SnNMR以及MS等数据确定了它们的分子结构。     

双环氮杂锡氧烷配合物反应性质研究——V.烷基化反应

首次讨论了双环氮杂锡氧烷配合物与卤代烷的烷基化反应,合成了5种新的双环氮杂锡氧烷配合物,并利用元素分析,IR,~1H NMR,~(119)Sn NMR以及MS等数据确定了它们的分子结构.     

三乙胺催化的双环氮杂锡氧烷配合物氘代反应研究

全面研究了三乙胺催化下双环氮杂锡氧烷配合物α 氢的氘代反应 .首先考察了三乙胺催化下双环氮杂锡氧烷配合物α 氢的氘代反应的核磁共振谱 ,研究发现 :在三乙胺存在下 ,有机锡配合物α 氢可以与CD3 OD溶剂发生氘代反应 ,其核磁共振峰强度随着时间而衰减 ,且氘代反应速率与三乙胺的浓度有关 .其次 ,利用核磁共振技术测定氘代反应速率 ,其反应表观速率常数为 2 .0× 1 0 -4 ～ 1 0 .0× 1 0 -4 s-1,推导了其动力学机理并讨论了取代基对氘代反应速率的影响 .     

双环氮杂锡氧烷配合物与醛的缩合反应的研究

含席夫碱双环氮杂锡氧烷配合物的结构与VB6酶体系结构相似。以含席夫碱二苯基锡配合物(PhSnL¹H)为研究对象,测定了二苯基锡配合物(PhSnL¹H)在DMSO中的pK_a(17.60),同时研究了该配合物与醛的缩合反应,合成了7种新的含β-羟基-α-氨基酸配体的有机锡配合物(PhSnL₁CHOHRⅠ～Ⅶ),并由IR、¹HNMR、¹¹⁹SnNMR及元素分析等确定了配合物的结构。     

双环氮杂锡氧烷配合物与醛的综合反应的研究

含席夫碱双环氮杂锡氧烷配合物的结构与ＶＢ６酶体系结构相似。以含席夫碱二苯基锡配合物为研究对象，测定了二苯基锡配合物在ＤＭＳＯ中的ＰＫｎ（１７．６０），同时研究了该配合物与醛的缩合反应，合成了７种新的含β－羟基－α－氨基酸配体的有机锡配合物，并由ＩＲ，＾１ＨＮＭＲ，＾１１９ＳｎＮＭＲ及元素分析等确定了配合物的结构。     

β-烷氧羰基乙基三氯化锡与单齿配体配合物的合成及酯交换反应

合成了16个β-烷氧羰基乙基三氯化锡与二甲基亚砜、N-氧化吡啶、吡啶等单齿配体的配合物，经过元素分析、IR、^1H NMR、TG-DTA等表征了其结构。报道了β-烷氧羰基乙基三氯化锡配合物和醇的酯交换反应，提出了其可能的反应机理。     

β-三芳基锗-α(β)-取代丙酸同1-乙氧基锡杂恶唑烷的 反应

利用β-三芳基锗-α(β)-取代丙酸同1-乙氧基锡杂恶唑烷的1-位取代反应,合成了15个1-[(β-三芳基锡-α(β)-丙酰氧基]-2,8,9-三氧杂-5-氮杂-1-锡杂三环[3,3,3,0^1.5]十一烷,并研究该反应规律,利用IR,NMR和MS表征了该类化合物的结构和质谱裂解机制,生物活性测定表明,它们只对某些细菌如溶血链球菌和金黄葡萄糖球菌有较好的抑制作用。     

1-(3-氨基丙基)-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷衍生物的合成及其抗肿瘤活性研究

通过1-(3-氨基丙基)-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷与酸反应或1-(3-氯丙基)-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷与胺反应,合成了14种1-(3-氨基丙基)-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷衍生物.体外细胞培养试验结果表明,某些1-(3-氨基丙基)-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷衍生物对艾氏腹水癌细胞具有较好的杀伤活性.     

具有生物活性的有机硅化合物的研究IX:1-(N-芳基呋喃甲酰胺)亚甲基-2,8,9-三氧杂-5-氮杂-1-硅杂三环[3.3.3.O^1^.^5]十一烷的合成

本文合成了六个1-(N-芳基呋喃甲酰胺)亚甲基-2,8,9-三氧杂-5-氮杂-1-硅杂三环[3.3.3.O^1^.^5]十一烷的化合物。合成方法简便, 反应时间短。易于后处理。经元素分析, IR, ^1H NMR, MS确定了新化合物的结构, 并经化合物3的X射线晶格衍射分析确定了该类化合物的空间排布情况。     

五配位锡(Ⅳ)有机化合物的合成与表征(Ⅲ)──含Fe-Sn-Fe三核金属有机配合物

5种氨基酸的Schiff碱及2种半卡巴腙分别与双-(茂基二羰基铁)二氯化锡反应制得7种新的含有Fe-Sn-Fe三核金属有机配合物,中心锡原子为五配位.合成反应产率较好,产品纯度也高.该类配合物的母体为双环氮杂锡氧烷.产物结构均经红外、核磁、质谱及元素分析确证.研究发现,氨基酸中α-碳上的取代基对铁上的茂环有影响.     

丝光沸石催化愈创木酚选择性烷基化反应的研究

本文研究了氢型丝光沸石催化愈创木酚(1)与莰烯(2)的选择性烷基化反应. 该烷基化反应产物萜基愈创木酚(3～6)中含5-异莰基愈创木酚(3a)25.0%, 经氢化, 氢解得萜基环己醇混合物, 含人造檀香主要成份反式-3-异莰基环己醇(7a)23.0%. 通过IR, ^1H NMR 和MS鉴定了烷基化产物色谱图中的5个主要化合物.     

Alkylation kinetics of proteins in preparation for two-dimensional maps: a matrix assisted laser desorption/ionization-mass spectrometry investigation

All existing protocols for protein separation by two-dimensional (2-D) gel electrophoresis require the full reduction, denaturation, and alkylation as a precondition for an efficient and meaningful separation of such proteins. Existing literature provides a strong evidence to suggest that full reduction and denaturation can be achieved in a relatively short time; the same thing, however, can not be said for the alkylation process, which the present study shows that more than 6 h are required for a complete alkylation. We have used matrix assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) to monitor protein alkylation by iodoacetamide over the period 0-24 h at pH 9. The present, fast and specific MS method provided clear indication on the extent and speed of alkylation which reached approximately 70% in the first 2 min, yet the remaining 30% resisted complete alkylation up to 6 h. The use of sodium dodecyl sulfate (SDS) during the alkylation step resulted in a strong quenching of this reaction, whereas 2% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) exerted a much reduced inhibition. The implications of the present measurements on 2-D gel analysis in particular and proteomics in general are discussed.     

Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold

We demonstrate a novel strategy for visualizing sequence-selective alkylation of target double-stranded DNA (dsDNA) using a synthetic pyrrole-imidazole (PI) polyamide in a designed DNA origami scaffold. Doubly functionalized PI polyamide was designed by introduction of an alkylating agent 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) and biotin for sequence-selective alkylation at the target sequence and subsequent streptavidin labeling, respectively. Selective alkylation of the target site in the substrate DNA was observed by analysis using sequencing gel electrophoresis. For the single-molecule observation of the alkylation by functionalized PI polyamide using atomic force microscopy (AFM), the target position in the dsDNA (～200 base pairs) was alkylated and then visualized by labeling with streptavidin. Newly designed DNA origami scaffold named "five-well DNA frame" carrying five different dsDNA sequences in its cavities was used for the detailed analysis of the sequence-selectivity and alkylation. The 64-mer dsDNAs were introduced to five individual wells, in which target sequence AGTXCCA/TGGYACT (XY = AT, TA, GC, CG) was employed as fully matched (X = G) and one-base mismatched (X = A, T, C) sequences. The fully matched sequence was alkylated with 88% selectivity over other mismatched sequences. In addition, the PI polyamide failed to attach to the target sequence lacking the alkylation site after washing and streptavidin treatment. Therefore, the PI polyamide discriminated the one mismatched nucleotide at the single-molecule level, and alkylation anchored the PI polyamide to the target dsDNA.     

Group 6 carbene complexes derived from lithiated azoles and the crystal structure of a molybdenum thiazolinylidene complex

Fischer-type (alkoxy)azolyl carbene complexes and Öfele–Lappert-type azolylinylidene complexes were synthesised by reaction of 1-phenylpyrazol-3-yllithium, 4-methylthiazol-2-yllithium, benzothiazol-2-yllithium, 1-methylimidazol-2-yllithium with M(CO)₅L (L=CO, THF or Cl⁻; M=Cr, Mo or W) and subsequent alkylation with CF₃SO₃CH₃. The alkylation of Fischer-type carbene complexes containing an azolyl as the organic substituent proceeded via ring opening of tetrahydrofuran. When the alkylation is carried out in THF, the carbocation CH₃O(CH₂)₄⁺ acts as an electrophile. Protonation rather than alkylation of coordinated imidazolyl furnished cyclic imine complexes. Changing the donor atom of a coordinated thiazole from N to C by deprotonation and alkylation afforded a carbene complex.     

Syntheses of (5E)-PGE2 and New 6-Functionalized Derivatives by the Use of Palladium-Catalyzed Decarboxylative Allylic Alkylation

(5 )-Prostaglandin E₂ (7) was synthesized fron ( )-4- -butyldimethylsilyloxy-2-cyclopentenone (1) by 2-alkenyloxycarbonylatlon of the organocopper conjugate-addition adduct (3) followed by intramolecular palladium-catalyzed decarboxylative allylic alkylation. The (5 )-prostaglandin E₂ skeleton was also obtained from the β-keto allylic ester (11) by a similar decarboxylative allylic alkylation. The decarboxylative allylic alkylation of another type of the three-component coupling product (12) gave new 6-methyleneprostaglandin E1 skeleton (15a), which was converted into new 6-methylprosta-glandin I methyl ester (20) 6-methyleneprostaglandin F₁ derivative (16) by two different ways. The stereochemistry of this intramolecular decarboxylative allylic alkylation was discussed in the reaction of 2-[( )- or ( )-2-butenyloxy-carbonyl] cyclopentanone systems.     

Total Synthesis of (-)-Tetrahydropalmatine via Chiral Formamidine Carbanions: Unexpected Behavior with Certain Ortho-Substituted Electrophiles

A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (+/-)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.     

Alkylating potential of α,β-unsaturated compounds

Alkylation reactions of the nucleoside guanosine (Guo) by the α,β-unsaturated compounds (α,β-UC) acrylonitrile (AN), acrylamide (AM), acrylic acid (AA) and acrolein (AC), which can act as alkylating agents of DNA, were investigated kinetically. The following conclusions were drawn: i) The Guo alkylation mechanism by AC is different from those brought about the other α,β-UC; ii) for the first three, the following sequence of alkylating potential was found: AN > AM > AA; iii) A correlation between the chemical reactivity (alkylation rate constants) of AN, AM, and AA and their capacity to form adducts with biomarkers was found. iv) Guo alkylation reactions for AN and AM occur through Michael addition mechanisms, reversible in the first case, and irreversible in the second. The equilibrium constant for the formation of the Guo-AN adduct is K(eq) (37 °C) = 5 × 10(-4); v) The low energy barrier (≈10 kJ mol(-1)) to reverse the Guo alkylation by AN reflects the easy reversibility of this reaction and its possible correction by repair mechanisms; vi) No reaction was observed for AN, AM, and AA at pH < 8.0. In contrast, Guo alkylation by AC was observed under cellular pH conditions. The reaction rate constants for the formation of the α-OH-Guo adduct (the most genotoxic isomer), is 1.5-fold faster than that of γ-OH-Guo. vii) a correlation between the chemical reactivity of α,β-UC (alkylation rate constants) and mutagenicity was found.     

2-Allyloxy/propargyloxypyridines: synthesis,structure, and biological activity

The alkylation (allylation and propargylation) of 3-cyano-6-dialkylamino-2-pyridones containing a d-annulated ring occurs at the oxygen atom. The structures of the starting compounds and their alkylation products were determined by X-ray diffraction. The neurotropic and antimicrobial activity of alkylation products was examined.     

Selective intercalation of charge neutral intercalators into GG and CG steps: implication of HOMO-LUMO interaction for sequence-selective drug intercalation into DNA

We have synthesized naphthopyranone epoxide 4 from D-isoascorbic acid together with its three diastereoisomers. DNA alkylation of ODNs containing 5'XGT3' and 5'TGY3' by 4 (11R, 13R), where X and Y are any nucleotide bases, occurred at all G residues except at G of the 5'TGC3' sequence. In contrast, the three other diastereoisomers of 4 showed only weak G alkylation activity. Differential (1)H NMR NOE of the 4-G adduct confirmed the G-N7 alkylation at the epoxide carbon of 4 with concomitant S(N)2 ring opening of the epoxide. Quantitative HPLC analysis of G alkylation efficiency for 4 showed the order of G alkylation susceptibility as TGGT approximately CGT > TGA > AGT > TGT > TGC. The order was fully consistent with those reported for aflatoxin B(1) oxide and kapurimycin A(3), suggesting that the sequence selectivity observed for these DNA alkylating agents is not structure dependent but most likely due to the intrinsic property of DNA sequences. We found that the order of G alkylation susceptibility obtained for 4 completely matched the calculated HOMO energy level of G-containing sequences. These results underscore that 4 is a unique molecular probe for ranking the HOMO level of G-containing sequences by well-known G alkylation chemistry and suggests that the intercalation of charge neutral intercalators is a HOMO-controlled process.