醇腈酶促不对称合成手性氰醇反应条件的研究

利用气相色谱手性分析,对醇腈酶促不对称合成手性氰醇中的pH值、温度、底物浓度和水含量对酶反应速度和非酶反应速度的影响作了研究。结果表明,上述因素对酶反应和非酶反应速度均有显著影响。在水含量较低的非水相酶反应体系中,pH值在4．0以下或反应温度为0－5℃时,非酶反应受到较大程度的抑制,而酶反应仍具有相对较快的反应速度,故可获得高光学纯度的产物。     

A Facile Synthesis of Squamosamide Cyclic Analogs

A series of novel cyclic derivatives have been synthesized by utilizing a nickel powder mediated radical cyclization as the key step. The structures of the new compounds were confirmed by ^lH-NMR and MS.     

Synthesis and Isolation of Diastereomers of Optically Active Cyclomercurated Ferrocenylimines

IntroductionOrganomercurials have been used extensively in organic synthesis and synthesis of other organometallics due to their ability to accommodate practically all the important organic functional groups and their ease in undergoing transmetallation for syntheses of transition metal organometallics which are very useful in organic synthesis. Recently, we reported the synthesis of optically active 1,2-disubstituted cyclomercurated ferrocenylimines by transmetallation reaction of planar chir…     

手征性杂氮钛三环化合物的合成

杂氮钛三环(titatrane)(Ⅰ)是一类具有五配体特殊结构的杂环化合物,由于对其合成工作研究的不多,所以这类化合物的一些性质还鲜为人知。我们对杂氮钛三环的合成方法做了改进,将手性中心引入到这类化合物中,合成了下列结构图中(Ⅱ)所示的具有手性的杂氮钛三环。     

脂蛋白脂酶激活剂艾溴利平类似物的合成

合成了两个新型的艾溴利平类似物——N-2 -硝基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰肼(5,总收率28.1％)和N-2-四氮唑基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(7,总收率30.5％).以对氯甲基苯甲酸为原料,经酯化、水解和酰氯反应制得中间体4-[(膦酸二乙酯基)甲基]苯甲酰氯(4);4与2-硝基-4-氯苯肼盐酸盐反应合成了5.4先与2-氨基-5-氯苯腈反应制得N-2-氰基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(6);6再与叠氮化钠反应合成了7.其结构经1 H NMR和IR表征.     

Attempt to Resolute Chiral Clusters by Optically Active Hydrazide

Due to the framework chirality optically active clusters can provide the proof that a cluster as a whole, and not one of its fragments, acts as a catalyst, most of the work have been directed to the synthesis of tetrahedron-type chiral clusters1-3. However, there remains another major problem to obtain the pure enantiomers. Although Vahrenkamp had obtained some pioneering results in this area before 19901, only several racemic chiral clusters have been separated into pure enantiomers until now…     

Synthesis of enantiopure 1,4-dioxanes, morpholines, and piperazines from the reaction of chiral 1,2-diols, amino alcohols, and diamines with vinyl selenones

The reactions of readily available vinyl selenones with enantiopure 1,2-diols, N-protected-1,2-aminoalcohols, and diamines gave substituted enantiopure 1,4-dioxanes, morpholines, and piperazines, respectively, in good to excellent yields. The same procedure was extended to the synthesis of thiomorpholine, benzodiazepine, and benzoxazepine. The reactions proceeded in one pot, in the presence of base, through a simple and novel application of the Michael-initiated, ring-closure (MIRC) reactions. The formed heterocycles constitute a framework that is observed in a large number of pharmaceutical compounds.     

Synthesis of Optically Active P‐Chiral and Optically Inactive Oligophosphines

A series of optically active P‐chiral oligophosphines (S,R,R,S)‐ 2 , (S,R,S,S,R,S)‐ 3 , (S,R,S,R,R,S,R,S)‐ 4 , and (S,R,S,R,S,R,R,S,R,S,R,S)‐ 5 with four, six, eight, and 12 chiral phosphorus atoms, respectively, were successfully synthesized by a step‐by‐step oxidative‐coupling reaction from (S,S)‐ 1 . The corresponding optically inactive oligophosphines 1′ – 5′ were also prepared. Their properties were characterized by DSC, XRD, and optical‐rotation analyses. While optically active bisphosphine (S,S)‐ 1 and tetraphosphine (S,R,R,S)‐ 2 behaved as small molecules, octaphosphine (S,R,S,R,R,S,R,S)‐ 4 and dodecaphosphine (S,R,S,R,S,R,R,S,R,S,R,S)‐ 5 exhibited the features of a polymer. Furthermore, DSC and XRD analyses showed that hexaphosphine (S,R,S,S,R,S)‐ 3 is an intermediate between a small molecule and a polymer. Comparison of optically active oligophosphines 1 – 5 with the corresponding optically inactive oligophosphines 1′ – 5′ revealed that the optically active phosphines have higher crystallinity than the optically inactive counterparts. It is considered that the properties of oligophosphines depend on the enantiomeric purity as well as the oligomer chain length.     

Base‐Dependent Stereodivergent Intramolecular Aza‐Michael Reaction: Asymmetric Synthesis of 1,3‐Disubstituted Isoindolines

The nucleophilic addition (A_N) / intramolecular aza‐Michael reaction (IMAMR) process on Ellman’s tert‐butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3‐disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza‐Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C₂‐symmetric bisacetate‐substituted isoindolines. In addition, bisacetate isoindolines bearing two well‐differentiated ester moieties are also noteworthy because they may allow for the orthogonal synthesis of β,β′‐dipeptides using a single nitrogen atom as a linchpin.     

Studies on the Synthesis of a Natural Product—Piceatannol and its Analogs

Piceatannol,(E)-3,3′,4,5′-tetrahydroxy stilbene, a natural polyhydroxy stibene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis,IR,MS and ^1H-NMR. Its analogs were synthesized by the similar method.     

Facile Access to Optically Active 2,6‐Dialkyl‐1,5‐Diazacyclooctanes

The chiral substituted 1,5‐diazacyclooctane (1,5‐DACO) is of considerable importance and has attracted attention from a wide range of fields due to their unique chemical and biological properties. Despite the application potential, further study has not been optimized due to difficulties in their synthetic accessibility. Here, we report that the 1,5‐DACO bearing a chiral auxiliary obtained from the formal [4+4] cycloaddition of N‐alkyl‐α,β‐unsaturated imines can be further derivatized by nucleophilic alkylation to give various chiral substituted 1,5‐DACO derivatives. The removal of the chiral auxiliary was effectively carried out using hydrogenation over Pearlman's catalyst. This methodology allows the production of a broad range of unprecedented optically active 2,6‐dialkyl‐1,5‐DACO, which could not be accessed by other methods.     

Optically Active Particles of Chiral Polymers

Particles constructed by chiral polymers (defined as PCPs) have emerged as a rapidly expanding research field in recent years because of their potentially wide‐ranging applications in asymmetric catalysis, enantioselective crystallization, enantioselective release, amongst many others. The particles show considerable optical activity, due to the chirality of the corresponding polymers from which the particles are derived. This review article presents an overview on PCPs with emphasis on our group's recent achievements in the preparation of PCPs derived from optically active helical polymers and their applications. PCPs can be prepared via emulsion polymerization, precipitation polymerization, and suspension polymerization by starting from monomers. Emulsification of preformed chiral polymers and self‐assembly approaches also can lead to PCPs. Chiral polymer‐based core/shell particles, hollow particles, and magnetic particles are also covered because of their remarkable properties and significant potential applications.

     

De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2-Hydroxy-1,4-diones with Nucleophiles

Herein, a divergent synthesis of a variety of 2α- and 5α-substituted furan derivatives from 2-hydroxy-1,4-diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6-conjugate addition or cyclization/Friedel–Crafts-type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6-conjugate addition for 5α substitution and >20 types for the Friedel–Crafts-type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity-oriented synthesis of α-substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4-hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.     

1,2-二氧六环类抗疟过氧化物的合成

Synthesis of five simple analogues of peroxyplakoric acid by using Kobayashi＇s method to construct the key 1,2-dioxane core is detailed.     

Bioinspired Total Synthesis of Sespenine

The first total synthesis of sespenine, a rare indole sesquiterpenoid from a mangrove endophyte, has been accomplished. A bioinspired aza‐Prins/Friedel–Crafts/retro Friedel–Crafts cascade reaction assembles the bridged tetrahydroquinoline core. Further investigations on the aza‐Prins cyclization imply that the C3 configuration of the hydroxyindolenine intermediate is crucial to the biosynthesis of sespenine and its congener xiamycin A.     

手性环胍衍生物的合成

以L-天冬酰胺为原料经十步反应合成了光学纯的手性双环胍, 总收率为2.2%. 这一合成方法的优点是避免使用剧毒的硫光气和气味难闻的有机硫化物     

Optically Active Chiral Auxiliary Benzyloxyphenylglycinol for Preparation of Oxazolidine and Its Derivatives

To investigate the recovery of amino alcohols as chiral auxiliaries, optically active p-benzyloxyphenylglycinol and its corresponding oxazolidine of 1-naphthylcarboxaldehyde were prepared. Grignard additions to the oxazolidine followed by electrophilic quench and acidic hydrolysis afforded an aldehyde( compound 8) (later it was reduced to an alcohol, compound 9) in an excellent enantiomeric excess and a good recovery of the chlral amino alcohol. This research provides a model study of chiral amino alcohols in solid phase asymmetric synthesis.     

New Optically Active Bis‐Heterocycles Derived from (S)‐Proline

Enantiomerically pure bis‐heterocycles containing a (S)‐proline moiety have been prepared starting from (S)‐N‐benzylprolinehydrazide ( 2b ). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N‐benzylprolinoyl residue. The structure of the tert‐butyl derivative 5d was established by X‐ray crystallography. Base‐catalyzed cyclization of 5 and 9 led to (S)‐3‐(pyrrolidin‐2‐yl)‐1H‐1,2,4‐triazole‐5(4H)‐thiones 6 and the corresponding 5(4H)‐one 8 , respectively, whereas, in concentrated H₂SO₄, compounds 5 undergo cyclization to give (S)‐5‐amino‐2‐(pyrrolidin‐2‐yl)‐1,3,4‐thiadiazoles 7 . Furthermore, 2b reacted with hexane‐2,5‐dione in boiling ⁱPrOH to yield the (S)‐N‐(2,5‐dimethylpyrrol‐1‐yl)prolinamide 10 . In the case of the bis‐heterocycle 8 , treatment with HCOONH₄ and Pd/C in MeOH gave the debenzylated product 12 .