Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dualspecificity tyrosine phosphorylation activated kinase 1A, casein 1,...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvidence for Fe(IV):O in the Molecular Mechanism of Action Trioxane Antimalarial ArtemisininGary H. Posner, Jared N. Cumming, Poonsakdi Ploypradith, and Chang Ho OhCite this: J. Am. Chem. Soc. 1995, 117, 21, 5885–5886Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 1995https://doi.org/10.1021/ja00126a042RIGHTS & PERMISSIONSArticle Views616Altmetric-Citations137LEARN ABOUT THESE METRICSArticle...

Nine C-10 non-acetal derivatives of the natural trioxane artemisinin (1) were prepared as dimers using some novel chemistry. As designed, each dimer was stable chemically. Olefinic 7 and saturated 8−13 all showed good to excellent antimalarial antiproliferative activities in vitro. Dimers 8, 10, 12 especially potent selective at inhibiting growth human cancer cell lines NCI vitro 60-cell line assay.

Abstract Shedding light on the lamellarins : Structural determinants for potent cytotoxic activity toward various cancer cell lines were systematically investigated to establish SARs marine alkaloids in lamellarin family. The C5C6 double bond ensures not only planarity of D‐ring, but also proper alignment substituents E‐ring with their respective moieties target. importance C7 OH group is revealed first time. magnified image Twenty‐two naturally occurring and three unnatural synthesized...

Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi−RC) of benzyldihydroisoquinoline α-nitrocinnamate derivatives, which provided 2-carboethoxypyrrole intermediates in moderate good yields (up 78% yield). Subsequent hydrogenolysis/lactonization furnished excellent 93% DDQ oxidation lamellarin acetates led directly corresponding...

Four new chromones, named harforamone A (1), B (2), C (3), and D (4), together with six known compounds (5–10) were isolated from the dichloromethane extract of stems Harrisonia perforata. The chemical structures four elucidated by spectroscopic analysis, including 1D, 2D NMR HRESIMS data. identified comparing their data previously reported Compounds 7 8 for first time Rutaceae family. in vitro cytotoxic activity against human cancer cell lines tested was evaluated, but none them showed any...

The new development of a transition-metal-free method for the synthesis THIQ-oxazol-2(3H)-one motif from exo-cyclic ene-carbamates by using hypervalent iodine as an oxidant is reported. Various functional groups substituted on aryl rings ene-carbamate substrates well N- and S-heterocyclic afforded corresponding products in up to 91% yield. Moreover, synthetic utility was highlighted phthalide-THIQ natural product, (±)-corlumine.

Herein, a three‐step general strategy featuring thermal intramolecular Diels‐Alder (IMDA) reaction to prepare the tricyclic 9‐methyl‐7‐aryl‐tetrahydro‐6H‐benzo[c]chromen‐6‐one core of morusalisin A is reported. This developed chemistry applicable synthesis variety tricycles, including 9‐silyloxy and 9‐phenyl‐7‐aryl‐tetrahydro‐6H‐benzo[c]chromen‐6‐ones. In addition, one‐pot dehydration/IMDA procedure was demonstrated. The positioning substituents on aryldiene moiety played significant role in...

Transannular carbocation cyclization of the achiral benzannulated cyclononene tertiary alcohols under acid catalysis furnished [5/6]‐fused tetracycles with three contiguous stereogenic centers, one which is an all‐carbon C11b quaternary center, in good to excellent yields and diastereoselectivity. Hydride, water, azide, allyl, electron‐rich (hetero)arenes could be employed as nucleophiles. The reaction both substrate‐ condition‐control. Further functionalization some selected substrates was...

Alkaloid achievement: Lamellarins, a new class of potential nontoxic inhibitors HIV-1 integrase that are also responsible for multidrug-resistance reversal in cancer cell lines, could be synthesized three chemical steps and 60 % overall yields from two simple starting materials (see scheme). The key step the convergent synthetic approach involved novel Michael addition/ring-closure reaction to give pyrrole core ester group required subsequent lactonization one step. Supporting information...

In only three chemical operations, natural trioxane lactone artemisinin (1) was converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds 4−9. The steps involved reduction, replacement the anomeric lactol OH by F using diethylaminosulfur trifluoride, and finally boron trifluoride-promoted substitution aryl, heteroaryl, acetylide nucleophiles. All these nonacetal, chemically robust, enantiomerically pure 4−9 have high antimalarial potencies in vitro against Plasmodium...

2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with ortho-quinone methides (o-QMs) which, in turn, generated by treating MOM-protected benzylacetate derivatives p-TsOH immobilized on silica (PTS-Si) toluene under mild conditions (0 degrees C to rt). The corresponding chromans obtained moderate excellent yields (42-97%) and diastereoselectivity (up >99:1).

The syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides types 9−13 are reported. In contrast to trioxanes the artemisinin family, but like yingzhaosu A arteflene, peroxide function compounds is contained a 2,3-dioxabicyclo[3.3.1]nonane system 6. Peroxides 9 10 (R1 = OH) readily available through multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a TOCO reaction). β-Sulfenyl peroxides converted into β-sulfinyl...

Abstract With the goal to improve aqueous solubility of lamellarins, lactone ring in their skeleton was replaced with a lactam moiety azalamellarins. However, reported synthetic route produced such derivatives very low yields. Hence, this study focused on developing an efficient simplified total scheme that could furnish both azalamellarins and parent lamellarins from same pyrrole ester intermediates. Subsequent comparative profiling revealed introduced lactone‐to‐lactam replacement rendered...

Oxyresveratrol (2,4,3′,5′-tetrahydroxystilbene, 1), a phytoalexin present in large amounts the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess wide variety biological activities. As part our continuing studies on structural modification oxyresveratrol, library twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic substitution. The two rings stilbene system 1 can be chemically modulated by exploiting different protecting groups....

On the basis of a mechanistic understanding mode action artemisinin-like antimalarials, series structurally simple 3-aryl-1,2,4-trioxanes 5 was designed and prepared in three to five operations from commercial reactants. The 3-aryl group attached each case as nucleophile. In an electronically complementary fashion, 3-(fluoroalkyl)trioxanes 6 were via attachment electrophilic fluoroalkyl esters. Both vitro vivo antimalarial evaluations these new trioxanes showed 12β-methoxy-3-aryltrioxanes...

Over 20 new, cyclic, peroxy ketals have been prepared via a two-step protocol starting with readily available aryl methyl ketones. Structure−activity correlations using in vitro antimalarial data as guide for optimization of potency led to the design and synthesis seven new peroxides that IC50 values 31−85 nM (artemisinin = 8.4 nM). Some SAR generalizations are discussed.

A series of new sulfide and sulfone 1,2,4-trioxanes was prepared in only a few steps from commercial reactants. The trioxanes were found to have higher vitro antimalarial potencies than the sulfides, with 12β-arylsulfone 1β being 13 14 as potent complex natural trioxane artemisinin (2). tentative chemical mechanism is proposed account for great difference activity 12α- vs. 12β-sulfide trioxanes.

A series of tetracyclic and tricyclic trioxane dimers has been prepared with ether ester tethers varying length flexibility. Several these have found to potent potentially therapeutically valuable antimalarial, antiproliferative, antitumor activities in vitro.

Five and six: 3,4-Cyclopentyl- cyclohexyl-fused 2-arylchromans could be readily prepared from the intramolecular hetero-Diels–Alder reactions of corresponding ortho-quinone methide (o-QM) precursors tethered to styrenes under mild reaction conditions. The products were obtained with good excellent diastereoselectivity (up to>99:1 dr; see scheme; MOM=methoxymethyl).