Preparation of ginkgolide and F-seco-ginkgolide lactols: the unique reactivity of α-hydroxy lactones toward NaBH4

It has been found that NaBH₄ smoothly reduces the α-hydroxy-lactone moieties in ginkgolide and F-seco-ginkgolides to lactols. The reaction is rapid and stops at the lactol stage; the coordination of NaBH₄ to the conformationally rigid cage structure is involved in both the initiation and termination stages. This facile reduction of ginkgolide lactones yields a variety of new ginkgolide lactols.     

Photochemical reactions of di-π-cyclopentadienyltitanium dichloride

Exchange of cyclopentadienyl ligands between molecules of titanocene dichloride in benzene solutions and alcoholysis of titanocene dichloride in methanol—benzene solutions occur exclusively by photochemical processes. The exchange of cyclopentadienyl ligands between titanocene dichloride and the titanocene monochloride dimer also occurs solely by a photochemical process.     

Bis(η-cyclopentadienyl)titanium(II) in the gas phase:: Mass spectrometric and computational study of the structure and reactivity

Bis(η⁵-cyclopentadienyl)titanium(II), titanocene, was generated in the gas phase by a thermolysis of the titanocene complex with bis(trimethylsilyl)acetylene. This elusive compound was characterized by means of mass spectrometric methods. Density functional theory (DFT) calculations indicated that the triplet ground state titanocene is kinetically stable towards the unimolecular isomerizations. Based on a DFT calculated energetics, a mechanism of the formation of a titanocene dimer, was proposed, which was based on a formation of bis(η⁵-cyclopentadienyl)titanium hydride as a key intermediate.     

Unusual behavior of methylidentriphenylphosphorane in reactions with seven-membered lactols

Methylidenetriphenylphosphorane in reactions with seven-membered lactols and their aluminates can act as a reducer converting them into the corresponding diols.     

Synthesis of polyquinanes via bicyclo [2.1.0] pentane intermediates. An easy access to optically pure diquinane alcohols of known absolute configuration.

The resolution of the cyclobutenic ester 1 using chiral lactols is described. After a stereospecific reaction sequence (cyclopropanation followed by an acidic solvolysis), the enantiomerically pure diquinanes 10 are obtained.     

The Role of a Metallocene Additive in Radically Initiated Polymerization when Solving Direct and Inverse Kinetic Problems

Polymerization of methyl methacrylate, initiated by benzoyl peroxide in the presence of titanocene dichloride, is considered from the point of view of formal kinetics. Based on the kinetic scheme of the process (which includes the reactions of classical radical polymerization, the reaction of benzoyl peroxide with titanocene dichloride, the reactions of the controlled radical polymerization of organometallic mediated radical polymerization (OMRP) and atom transfer radical polymerization (ATRP), the reaction of the formation of a coordinating active site and the coordinating chain propagation on a mathematical model of the kinetics of the process is created. This model also makes it possible to calculate the molecular-mass characteristics of poly(methyl methacrylate). As a result of the solution of the inverse kinetic problem at a temperature of 343 K, the values of the reaction rate constants of the kinetic scheme are found under which the discrepancy between the calculated models and experimental data is minimal. Using the developed model of the kinetics of the process, a numerical experiment is performed (i.e., a direct kinetic problem is solved). This problem revealed the following regularities of the process. (1) An increase in the initial concentration of titanocene dichloride at a constant initial concentration of benzoyl peroxide leads to an increase in the rate of consumption of benzoyl peroxide but not to an increase in the initial rate of the process compared to classical radical polymerization. (2) With an increase in the initial concentration of titanocene dichloride, the lifetime of the macroradicals at the initial stage of the process is reduced, and hence the molecular weight of the resulting polymethyl methacrylate is less than that of the polymethyl methacrylate obtained in the absence of titanocene dichloride, and it will increase during the process of approaching the final values. (3) During the polymerization of methyl methacrylate, initiated by benzoyl peroxide in the presence of titanocene dichloride, a smoothing gel effect (as in the case of the polymerization of methyl methacrylate initiated by benzoyl peroxide in the presence of ferrocene) does not occur since titanocene dichloride forms stable complexes with methyl methacrylate and, consequently, it participates in reactions consuming macroradicals to a lesser degree than ferrocene.     

Electrochemical Study of Highly Substituted Titanocene Dihalides

Titanocene dihalides are promising alternative to Cisplatin in cancer chemotherapy which should reduce negative side effects and overcome increasing resistance of cancer cells. Since the mechanism of anti‐cancer action is associated with generation of reactive oxygen species (ROS), hence with redox processes, electrochemical investigation of titanocene species would be an important issue, not applied up to now. In this article we report on the electrochemical reduction as well as oxidation of titanocene difluorides and dichlorides where unsubstituted as well as highly substituted titanocene dihalides are compared. The experiments were realized in acetonitrile using various electrode materials. The studied series was completed by a new dimethylsilylene bridged ansa‐titanocene difluoride which was characterized by NMR and x‐ray crystallography. The influence of structure and substitution on the redox properties was evaluated and, in addition to this, cytotoxicity of studied titanocene dihalides against human ovarian cancer cell lines A2780 and SK‐OV‐3, as well as against human embryonic kidney cell line HEK293 were screened. Two of highly substituted titanocenes exhibit cytotoxicity comparable with that of Cisplatin.     

Experimental and theoretical studies on stereo- and regioselectivity in intramolecular nitrone-alkene cycloaddition of hept-6-enoses derived from carbohydrates

The effect of blocking groups and stereochemistry of the substituents on the regio- and stereoselectivity in intramolecular nitrone-alkene cycloaddition (INAC) of hept-6-enoses are reported. L-ribo-Hept-6-enose 12 and D-lyxo-hept-6-enose 15, both containing a 2,3-O-isopropylidene blocking group, and L-xylo-hept-6-enose 23 and D-arabino-hept-6-enose 30, both with a 2,3-O-trans-diacetal blocking group, were prepared from D-ribose and D-arabinose, respectively. With N-alkyl hydroxylamine, lactols 12 and 15 underwent an INAC reaction to give cis-fused isoxazolidines exclusively whereas lactols 23 and 30 gave a mixture of cis-, trans-fused isoxazolidines (cyclohexanols) and bridged isoxazolidines (cycloheptanols). With the 2,3-O-trans-diacetal protecting group, the bridged bicyclo[4.2.1]isoxazolidines (cycloheptanols), via the endo mode of INAC cyclization, were synthesized for the first time from unbranched sugar derivatives 23 and 30. The stereochemical outcomes of these reactions were rationalized on the basis of transition state energies obtained by computation. The present INAC showed trivial temperature, but significant solvent dependence. For lactols 23 and 30, performing the INAC in 2-propanol gave the best yields of fused isoxazolidines (cyclohexanols) whereas in dichloromethane afforded the best yields of bridged isoxazolidines (cycloheptanols).     

Zum verhalten von cyclopentadienyltitan(IV)komplexen in wässrigem medium. Titanocenkomplexe als cancerostatica

Complexes of titanocene are hydrolyzed in aqueous solution, leading to insoluble polymeric {(CpTiO)₄O₂}_∞ at pH 5.5. For this reason soluble titanocene complexes do not exist in animal tissue and so the cancerostatic activity suggested for complexes such as cis-platinum(II) is improbable. Various observations, however, show cyclopentadiene, formed by the hydrolytic cleavage of the titanocene complex to be a cancerostatic agent.     

Ethylene Polymerization with Cycloalkylidene‐Bridged Cyclopentadienyl Metallocene Catalysts

Ethylene was polymerized with cycloalkylidene‐bridged cyclopentadienyl metallocene catalysts 1 – 9 in the presence of methyl aluminoxane (MAO) as the cocatalyst. Unlike the normal titanocene catalysts, the cycloalkylidene‐bridged cyclopentadienyl titanocene catalysts show much higher activities than the corresponding zirconocene and hafnocene catalysts and show the highest activities at higher temperature. This indicates that the cycloalkylidene‐bridged cyclopentadienyl titanocene system is very thermally stable and maybe a very promising catalyst system for industrial application.     

Stereoselective synthesis of C-alkyl and functionalised C-alkyl glycosides using ‘thiophene’ as a masked C-4 synthon

Synthesis of C-alkyl and functionalised C-alkyl glycosides is achieved by desulphurisation of the corresponding thiophene glycosides, wherein ‘thiophene’ is utilised as a masked four-carbon synthon. Thiophene glycosides in turn were prepared from the corresponding sugar lactols.     

One-pot synthesis of cyclic nitrones and their conversion to pyrrolizidines: 7a-epi-crotanecine inhibits alpha-mannosidases

[reaction: see text] A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. Its efficiency relies on the condensation of unprotected hydroxylamine with readily available lactols and on the chemoselectivity of the subsequent esterification with methanesulfonyl chloride. The targeted enantiomerically pure pyrroline N-oxides are versatile synthetic intermediates: one of the nitrones so-obtained has been converted into new polyhydroxypyrrolizidines, analogues of the alkaloids rosmarinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.     

二茂钛全氟有机酸衍生物的合成和抑瘤试验

本文报道了一类新的二茂钛全氟有机酸衍生物的合成,并发现其中1,2,3三个二茂钛全氟二元酸衍生物,对小鼠艾氏腹水癌有明显的抗癌活性。     

Lactone-free ginkgolides via regioselective DIBAL-H reduction

The lactone rings of ginkgolide A are converted into corresponding tetrahydrofuran moieties via DIBAL-H reduction followed by deoxygenation of the formed lactols with Et3SiH-BF3.Et2O to produce a series of lactone-free ginkgolides.     

A one-pot procedure for methylenating carbonyl compounds using the Nysted reagent and titanocene dichloride

The combination of the Nysted reagent and titanocene dichloride methylenates aldehydes and ketones to give alkenes, and in a microwave-assisted process, esters and lactones give enol ethers. The methylenating agent in this one-pot procedure is presumed to be titanocene methylidene, which is the same reactive intermediate as that generated from Tebbe, Petasis and Grubbs reagents, each of which have to be prepared before use.     

水溶性茂钛配合物的表征及其在芳香酸茂钛衍生物合成中的应用

二氯二茂钛与5－磺基水杨酸形成了较为稳定的水溶性配合物。由等摩尔系列 法确定了其组成为1:1,通过对含5－磺基水杨酸二茂钛配离子的不溶性配合物1的 结构分析表明,其中的羧基以双齿形式与钛配位,形成了四元环状结构。首次利用 该水溶性配合物在水相和两体系中得到了八种新的二茂钛芳香酸衍生物,为配合物 2 ～ 9。运用元素分析、IR及~1H NMR对它们的组成和结构进行了表征,结果表明 ,这八种配合物中羧基均以单齿形式与钛配位,且不含5－磺基水杨酸配体。     

Synthesis of medium-sized lactones: Iodosobenzene diacetate an efficient reagent for β-fragmentation of alkoxy-radicals

Photolysis of several steroidal lactols in the presence of iodosobenzene diocetate (IBDA) and iodine leads to alkoxy-radicals, which undergo β-fragmentation to produce medium-sized lactones in good yields.     

The rearrangement of some cyclopentanone-aryloximes: synthesis of (±)-aplysin, (±)-filiformin and of their debromo analogues.

Upon acid catalyzed rearrangement after Sheradsky, the aryloximes A gave the tricyclic aminals C, which suffered hydrolysis to lactols E. The unique alcohol 29 was then prepared through a highly stereoselective equilibration-reductive alkylation of the epimeric mixture of lactols 22a,b. Two routes, one of which was stereospecific, allowed cyclization of 29 to (±)-aplysin 34. The yield was 2.5 % from oximes 2a,b. The isomeric epi-aplysin 35 and filiformin 36 were also obtained from 29. The debromo analogues 37,38 and 39 and their trideutero derivatives 41,42 and 43 were synthesized along similar line and allowed unequivocal structure elucidation by NMR spectroscopy.     

A new route to spiro-ketals using the Horner-Wittig reaction of 2-diphenylphosphinoxy cyclic ethers

Two insect pheromones along with other spiro-ketals have been synthesised by a new route which involves Horner-Wittig coupling of 2-diphenylphosphinoxy cyclic ethers with aldehydes and lactols followed by acid catalysed cyclisation.     

Iodocyclisation of unsaturated lactols and acetals. A new route to furo-2,3b-furans and pyrans.

Cyclisation by iodine or other electrophilic reagents of unsaturated lactols or acetals has been studied and proved to be an efficient route to substituted furo-2,3b-furans or pyrans.