Polyprenylated Benzoylphloroglucinols with DNA Polymerase Inhibitory Activity from the Fruits of Garcinia schomburgkiana.

Chemical investigation of the fruits of Garcinia schomburgkiana collected in Vietnam led to the isolation of eight new schomburgkianones, A-H (1-8), four known (9-12) polyprenylated benzoylphloroglucinols, and four known biflavonoids. The structures of these compounds were elucidated by spectroscopic and chemical means. The absolute configuration at C-40 of 1 and 2 was determined by (1)H NMR analyses of their MPA esters.

Alkaloids from the Tuber of Stephania cf. rotunda.

Chemical investigation of the tuber of Stephania cf. rotunda collected in Vietnam led to the isolation of a new stephaoxocane-type alkaloid, stepharotudine (1), twenty -eight known alkaloids, and two known amides. The chemical structures of the isolated compounds were determined by spectroscopic and chemical methods.

Serotonergic mechanisms are involved in antidepressant-like effects of bisbenzylisoquinolines liensinine and its analogs isolated from the embryo of Nelumbo nucifera Gaertner seeds in mice.

Objectives: We attempted to ascertain if bisbenzylisoquinoline alkaloids, liensinine and isoliensinine from Nelumbo nucifera Gaertner have antidepressant-like effects and compare the effects with those previously obtained by their analogue neferine.

Methods: Using mice, the forced swimming test (FST) was carried out after treatment with liensinine, isoliensinine and neferine.

Key Findings: Liensinine and isoliensinine elicited antidepressant-like effects in mice after the FST.

Synthesis and pharmacological activity of alkaloids from embryo of lotus, Nelumbo nucifera.

Bisbenzylisoquinoline alkaloid, nelumboferine which was recently isolated from the embryo of Nelumbo nucifera, and stereoisomers of neferine, which is a major alkaloid of the embryo of N. nucifera, were stereoselectively synthesized. Pharmacological activity of nelumboferine, stereoisomers of neferine, liensinine, isoliensinine, and O-methylneferine were evaluated.

Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth.

We previously found six compounds of alkyl p-coumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of p-coumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth.

Antidepressant-like effects of neferine in the forced swimming test involve the serotonin1A (5-HT1A) receptor in mice.

The effects of neferine, an alkaloid of Nelumbo nucifera Gaertner embryos, on immobility in the forced swimming test, which is used to evaluate antidepressants, were investigated in mice. The administration of neferine from 25 to 100 mg/kg i.p.

Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae.

A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (-)-5-hydroxy-2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (-)-8-hydroxy-2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1.

Synthesis and DNA polymerase alpha and beta inhibitory activity of alkyl p-coumarates and related compounds.

trans- and cis-Icosyl, docosyl, and tetracosyl p-coumarates, constituents of Artemisia annua L., and their structurally-related compounds were synthesized and evaluated for inhibitory activity on DNA polymerases alpha and beta. Among 30 compounds synthesized, octadecyl trans- and cis-p-coumarates and octadecyl p-hydroxyphenylpropiolate showed strong inhibitory activity on DNA polymerases alpha and beta.

Total synthesis of (-)-lycorine and (-)-2-epi-lycorine by asymmetric conjugate addition cascade.

Total syntheses of (-)-lycorine and (-)-2-epi-lycorine were accomplished using chiral ligand-controlled asymmetric cascade conjugate addition methodology, which enables the formation of two C-C bonds and three stereogenic centers in one pot to give synthetically useful chiral cyclohexane derivatives.

Stereoselective synthesis and cytotoxicity of a cancer chemopreventive naphthoquinone from Tabebuia avellanedae.

Stereoselective synthesis of 1, one of biologically active naphthoquinones from a Brazilian traditional medicine Tabebuia avellanedae, was achieved by utilizing Noyori reduction as a key step. Compound 1 displayed potent cytotoxicity against several human tumor cell lines, whereas it showed lower cytotoxicity against some human normal cell lines compared with that of mitomycin. On the other hand, its enantiomer was less active toward the tumor cell lines than 1.

Mechanistic aspects of thiyl radical-promoted acyl radical cyclization of formylenoate-cyclization versus oxidation.

Treatment of formylalkenoates 1 and 7 with 2,2'-azobis(2-methylpropanenitrile) (AIBN) in the presence of dioxygen gave oxygenated carboxylic acids 5, 6, 8, 9 instead of acyl radical cyclization products, through preferential reaction of the corresponding acyl radicals with dioxygen rather than intramolecular attack to an enoate moiety. The reaction of 1 with AIBN in the absence of dioxygen recovered starting 1 in 98% yield.

Thiol-catalyzed acyl radical cyclization of alkenals.

Thiol-catalyzed direct generation of acyl radicals and their intramolecular addition to olefins of alkenals gave 2-substituted five- and six-membered cyclic ketones in reasonably good yields. The combination of odorless tert-dodecanthiol and AIBN or V-40 was the initiator of choice among surveyed radical generators for the cyclization of alkenals. Aldehydes having electron-deficient olefins cyclized more easily than those having unactivated olefins.

Synthesis of nitrogen-functionalized cyclohexanes using chemoselective conjugate addition of phenyllithium to linear omega-nitro-alpha,beta,psi,omega-unsaturated ester and subsequent stereoselective intramolecular nitro-Michael cyclization.

Nitrogen-functionalized cyclohexane derivatives with three contiguous chiral centers were synthesized by nitroalkene-selective conjugate addition of phenyllithium to a omega-nitro-alpha,beta,psi,omega-unsaturated ester and subsequent stereocontrolled intramolecular nitro-Michael cyclization with cesium fluoride and a quaternary ammonium bromide. The cyclohexanes were applicable to the total synthesis of alpha-, beta- and gamma-lycoranes.

Molecular assembly of C2-symmetric Bis-(2S)-2-methyldodecanoylamides of alpha,omega-alkylidenediamines into coiled coil and twisted ribbon aggregates.

A series of 10 didodecanoylamides of alpha,omega-alkylidenediamines bridged by a straight carbon chain varying in length from 0 to 9 carbons was examined as possible gelator molecules of organic liquids to gain information on the relationships between the spacial arrangement of two amide groups in a molecule and their effects on the microscopic structures of the gel. The structural characteristics of these amides are parallel and antiparallel arrangements of two amide carbonyl groups, which depend on the even and odd numbers of a bridging zigzag carbon chain. The linear alkyl chain moieties and a center carbon chain of diamides intermolecularly interact with each other within the van der Waals contact.

Total synthesis of (+/-)-alpha- and beta-lycoranes by sequential chemoselective conjugate addition-stereoselective nitro-Michael cyclization of an omega-nitro-alpha,beta,psi,omega-unsaturated ester.

[reaction: see text] An omega-nitro-alpha,beta,psi,omega-unsaturated ester underwent a chemoselective conjugate addition of a nitroolefin moiety with aryllithium to produce a psi-aryl-omega-nitro-alpha,beta-unsaturated ester, which was then stereoselectively cyclized by intramolecular nitro-Michael reaction giving a functionalized cyclohexane applicable to the total synthesis of (+/-)-alpha- and beta-lycoranes.

Asymmetric conjugate addition of arylthiols to enoates and its application to organic synthesis of biologically potent compounds.

As a part of our studies aimed at asymmetric catalytic reactions by using an external chiral ligand, we have developed a catalytic asymmetric addition reaction of an arylthiol to alpha,beta-unsaturated esters under the control of an external chiral ligand. The characteristic of our technology is a double activation of a thiol by lithiation and chelate formation with a chiral tridentate amino diether ligand, which simultaneously and effectively controls a stereochemistry of the reaction. One significant feature of an arylthiol is a bulky 2-substitution on aryl group, which enables the formation of a really reactive monomeric thiolate species.

Chiral amino ether-controlled catalytic enantioselective arylthiol conjugate additions to alpha,beta-unsaturated esters and ketones: scope, structural requirements, and mechanistic implications.

Asymmetric conjugate addition reaction of 2-trimethylsilylbenzenethiol with enoates and enones is catalyzed by a chiral amino ether-lithium thiolate complex and affords adducts with high enantioselectivity. Both the s-cis conformation and a steric wall at one side of the carbonyl group are structural requirements in substrates yielding adducts with high enantioselectivity. Reactions with tert-butyl enones gave addition products with high enantioselectivity.

Catalytic Enantioselective Protonation of Lithium Ester Enolates Generated by Conjugate Addition of Arylthiolate to Enoates.

A chiral ligand, a catalytic amount of lithium cation, and no chiral proton source: These are features of the present asymmetric addition-protonation of propenoates with 2-trimethylsilylbenzenethiol. The reaction is catalyzed by a combination of lithium 2-trimethylsilylbenzenethiolate and the chiral ligand 1. Desulfurization of the product affords 2-substituted propanoates with high ee values and without racemization.