Antiplasmodial,cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul.(Celastraceae)originated from Madagascar

Objective:To validate scientifically the traditional use of Salacia leptoclada Tul.(Celastraceae)(S.leptoclada)and to isolate and elucidate the structure of the biologically active compound.Methods:Bioassay-guided fractionation of the acetonic extract of the stem barks of S.leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models.The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry.Results:Biological screening of S.leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide.The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC_(50)value of(0.041±0.020)μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC_(50)value of(0.052±0.030)μg/mL.Despite this interesting anti-malarial property of the lead compound,the therapeutic index was weak(0.788).In the best of our knowledge,the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S.leptoclada.Conclusions:The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug.

1,6-Conjugate addition of para-quinone methides using gem-diborylcarbanions: Practical access to gem-diborylalkanes bearing vicinal tertiary/quaternary stereocenters

A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.

DNA alkylation promoted by an electron-rich quinone methide intermediate

Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.

Photoinduced reaction of potassium alkyltrifluoroborates,sulfur dioxide and para-quinone methides via radical 1,6-addition

A photoinduced reaction of potassium alkyltrifluoroborates,sulfur dioxide,and para-quinone methides under visible light irradiation at room temperature is developed,giving rise to diarylmethyl alkylsulfones in moderate to good yields.This reaction works well under photocatalysis with a broad substrate scope by using DABCO·(SO_(2))_(2)as the source of sulfur dioxide.Mechanistic study shows that this transformation is initiated by alkyl radicals generated in situ from potassium alkyltrifluoroborates in the presence of photocatalyst.The subsequent insertion of sulfur dioxide and radical 1,6-addition of para-quinone methides with alkylsulfonyl radical intermediates afford the corresponding diarylmethyl alkylsulfones.

Transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates:Access to different sized medium-sized heterocycles

Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis.Herein,we developed a transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates by controlling the steric hindrance of substituent.Different from reported alkoxide-triggered annulations,this process undergoes a regiodivergent allylation of para-quinone methides followed by 1,6-addition reaction,providing a new route to selectively synthesize seven-to ten-membered nitrogen-containing heterocycles in high yields with excellent regioselectivities.This protocol features a broad substrate scope,wide functional group tolerance as well as operational simplicity.The reaction mechanism was investigated by conducting a series of control experiments as well as DFT calculations and the origins of the regioselectivities of the cycloaddition process were rationalized.

Synthesis of 4H-chromenes by silver(Ⅰ)-catalyzed cycloaddition of ortho-quinone methides with N-allenamides

Chromenes represent an important class of six-membered heterocycles and have drawn tremendous attention in recent years. In this article, we report a convenient and practical synthesis of this heterocycle by a silver(I)-catalyzed cycloaddition reaction between in situ generated ortho-quinone methides and N-allenamides. Diverse 4H-chromenes were synthesized in good to excellent yields under very mild conditions.

Synthesis of 9-phenol-substituted xanthenes by cascade O-insertion/1,6-conjugate addition of benzyne with ortho-hydroxyphenyl substituted para-quinone methides

The cascade O-insertion/1,6 conjugate addition between benzynes and ortho-hydroxyphenyl substituted para-quinone methides has been reported, affording 9-phenol substituted xanthenes in 49%-84% yields.

Visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates: An approach to 2,3-dihydrobenzofuran derivatives

A visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates is developed. This one-pot two step reaction offers a mild and efficient approach for the synthesis of biologically important 2,3-dihydrobenzofuran derivatives in good yields and moderate diastereoselectivities.

Transition-metal-free synthesis of 1,4-benzoxazepines via[4+3]-cycloaddition of para-quinone methides with azaoxyallyl cations

A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transition-metal free,room temperature,cheap inorganic base)and provides a very efficient route to a series of biologically important 1,4-benzoxazepine derivatives in good to excellent yields.

Organocatalytic cascade 1,6-conjugate addition/annulation/tautomerization of functionalized para-quinone methides： Access to chiral 2-amino-4-aryl-4H-chromenes

A novel organocatalytic cascade process initiated by 1,6-conjugated addition has been successfully developed. A range of pharmaceutically active 2-amino-4-aryl-4H-chromenes were readily obtained in high yields（88%-99%） and excellent enantiopurities（86%-99% ee）. The functionalized para-Quinone methides（p-OMs） could be facilely obtained.

A Concise Synthesis of 2-(2-Hydroxyphenyl)acetonitriles via the o-Quinone Methides Generated from 2-(1-Tosylalkyl)phenols

A concise synthesis of 2-(2-hydroxyphenyl)acetonitriles has been developed through reaction of trimethylsilyl cyanide and the o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols under basic conditions.In addition,2-(2-hydroxyphenyl)acetonitriles could be conveniently transformed to benzofuranones.

A Unified Variational Principle of Fluid Mechanics and Application on Solitary Subdomain or Point

-According to basic equations of fluid mechanics, this paper presents a unified variational principle of fluid mechanics (UVPFM) by using the optimization method of weighted residuals (OMWR). The advantages are as follows, the establishment of the functional and the variational principle is easy, it can change various problems of fluid mechanics derived by basic equations into a unified optimization problem, and the solution is the optimum one in some sense. According to the OMWR for the solitary subdomain, this paper uses UVPFM onto any solitary subdomain and gives the solution of the hydrodynamics equation which is suitable only for that solitary subdomain. According to the OMWR for solitary point, this paper uses UVPFM to any solitary point and gives the solution of the hydrodynamics equation (point solution) which is suitable only for that solitary point. As the solution for the solitary subdomain or solitary point is developed independently, the compatibility with other subdomain or other points, does not need to be considered, but all the boundary conditions and the supplementary derived residual equations obtained by running the derivative operations to the differential equation should be taken into account.

Diastereodivergent formal[4+1]cycloaddition of azoalkenes as one-carbon synthons

The first diastereodivergent formal[4+1]cycloaddition reactions of azoalkenes with p-quinone methides(pQMs)have been accomplished.The reported reaction occurred via a domino oxa-1,4-addition/1,6-addition process,allowing the use of common azoalkenes as C1 synthons.A broad range of 2,3-dihydrobenzofurans was smoothly prepared in good yields and with reversible diastereoselectivities.The steric hindrance and hydrogenbonding interaction were proposed to account for the two different modes of diastereo-control.The projected reaction features the employment of azoalkene as carbene-like C1 synthon,mild conditions,broad substrate scope and tunable diastereoselectivity.

Diastereoselective synthesis of spiro[chromane-3,30-indolines]and spiro[chromane-3,20-indenes]via DBU promoted formal[4+2]cycloaddition reaction

A new DBU-catalyzed formal[4+2]cycloaddition between ortho-hydroxyphenyl-substituted para-quinone methides and electron-deficient dienophiles including 3-methyleneoxindoles and 2-aryldeneindene-1,3-diones was established.A wide range of functionalized spiro[chromane-3,30-indolines]and spiro[chromane-3,20-indenes]were successfully synthesized in good yields and with high diastereoselectivity.The features of the reaction included readily available substrates,mild reaction conditions,convenient methodology and good functional group tolerance.