- Conversion of camptothecins to mappicine ketones using silica gel supported sodium hydrogen sulfate catalyst
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Silica gel supported sodium hydrogen sulfate (NaHSO4.SiO2) catalyst has been utilized for the conversion of camptothecin and 9-methoxycamptothecin to mappicine ketone, an antiviral lead compound and its analogue, 9-methoxymappicine k
- Das, Biswanath,Madhusudhan
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- Preparation of mappicine ketones from camptothecins: Chemistry of the camptothecin E ring
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Camptothecin and its analogs are thermolyzed at 150-200 °C to yield mappicine ketone derivatives by loss of carbon dioxide from the α- hydroxylactone.
- Fortunak,Mastrocola,Mellinger,Wood
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- Two efficient methods of the conversion of camptothecin to mappicine ketone, an antiviral lead compound
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Two simple and efficient methods for the conversion of the naturally occurring alkaloid, camptothecin to mappicine ketone, an antiviral lead compound, have been described. The first method involved the treatment of camptothecin with borontrifluoride etherate and the second method utilised the microwave irradiation of the alkaloid.
- Das, Biswanath,Madhusudhan,Kashinatham
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- Traceless solid-phase synthesis of mappicine ketone library via multiple chemoselective palladium-catalyzed reactions on benzenesulfonate linker
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We report here a solid-phase synthesis of a library of mappicine ketone, a leading antiviral compound with activity against herpes viruses and human cytomegalovirus. The synthesis is based on multiple chemoselective palladium-catalyzed reactions involving
- Tsukamoto, Hirokazu,Suzuki, Risako,Kondo, Yoshinori
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experimental part
p. 2005 - 2010
(2009/04/10)
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- Total synthesis of nothapodytine B and (±)-mappicine
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A novel, efficient total synthesis of the naturally occurring antiviral nothapodytine B (2, mappicine ketone) is reported. The approach is based on the successful implementation of the Johnson orthoester rearrangement of allylic alcohol 7 for assembly of a pyridone D ring precursor with the necessary functionalities. Nothapodytine B is converted into mappicine by NaBH4 reduction.
- Chavan, Subhash P.,Sivappa, Rasapalli
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p. 3941 - 3943
(2007/10/03)
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- Total synthesis of mappicine ketone (nothapodytine B) by means of sulfur-directed 5-exo-selective aryl radical cyclization onto enamides
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Enamides 5, on treatment with Bu3SnH-AIBN, underwent aryl radical cyclization in a 5-exo manner to give 1-[bis(phenylthio)methyl]dihydroisoindoles 6, which were partially desulfurized with Bu3SnH-AIBN to give 1-mono(phenylthio)methyl
- Kato, Issei,Higashimoto, Masayuki,Tamura, Osamu,Ishibashi, Hiroyuki
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p. 7983 - 7989
(2007/10/03)
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- Synthesis of (+/-) mappicine and mappicine ketone
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Mappicine and mappicine ketone are camptothecin analogs of interest as antiviral agents. A novel synthesis of these compounds is described using a Friedlander condensation. The requisite ketone is prepared via a regioselective ortho-directed metallation/a
- Henegar, Kevin E.,Baughman, Ted A.
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p. 601 - 605
(2007/10/03)
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- A Modular Approach to Oxoindolizino Quinolines: Efficient Synthesis of Mappicine Ketone (Nothapodytine B)
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A general route to oxoindolizino quinolines, such as nothapodytine A, mappicine, camptothecin, and several chemotherapeutic derivatives, is illustrated by the synthesis of the antiviral natural product from Nothapodytes foetida, mappicine ketone (R1 = R4 H, R2 = CH3, R3 = COC2H5). A wide range of new camptothecinoids should now be readily available for biological testing.
- Raolji, Gajendra B.,Garcon, Stephanie,Greene, Andrew E.,Kanazawa, Alice
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p. 5059 - 5061
(2007/10/03)
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- 2-Pyridones from cyanoacetamides and enecarbonyl compounds: Application to the synthesis of nothapodytine B
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The condensation of an enone or enal with cyanoacetamide derivatives and t-BuOK furnishes either 3-cyano-2-pyridones or 3-unsubstituted-2-pyridones, depending on whether the reaction is carried out in the presence or in the absence of O2. In the first case, in situ oxidation of Michael-type intermediates takes place; in the second case, the products result from "decyanidative aromatization" of such intermediates. A one-step synthesis of 3-alkyl-2-pyridones has been devised on the basis of decyanative union of an enone/enal and a 2-alkylcyanoacetamide. The new reaction forms the centerpiece of an unusually concise synthesis of nothapodytine B (mappicine ketone).
- Carles, Lionel,Narkunan, Kesavaram,Penlou, Sebastien,Rousset, Laurence,Bouchu, Denis,Ciufolini, Marco A.
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p. 4304 - 4308
(2007/10/03)
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- Preparation of camptothecin and nothapodytine derivatives
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The invention concerns the preparation of nothapodytine or camptothecin derivatives which consists in causing 4-ethyl 2methyl hepta-2,4-dienoic acid act on a 3-aminomethyl 2-bromo quinoline derivative (III) wherein R1and R2are H or R1is a halogen atom or alkyl, R2is a O—CO—X radical as defined for the camptothecin derivatives; or R1and R2are defined for the known camptothecin derivatives or represent protected radicals or radicals easily convertible into the radicals R1and R2, to obtain the quinoline derivative (IV); adding to the resulting quinoline derivative (2-methoxy carbonyl vinyl) tributyltin in the presence of a complex of palladium and triphenylarsin to obtain the quinoline derivative (V); cyclizing the resulting quinoline derivative to obtain the tetracyclic derivative (VI); then in subjecting said derivative to an ozonolysis followed by treatment with dimethyl sulphide to obtain the tetracyclic derivative (VII); saponification followed by decarboxylation in oxidising conditions of the resulting tetracyclic derivative to obtain the nothopodytine derivative (VIII); then optionally transforming the resulting derivative into a camptothecin derivative or into a mappicine derivative.
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- New Pyridone Approach: Total Synthesis of Mappicine Ketone (Nothapodytine B)
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A novel synthesis of mappicine ketone, which possesses strong selective activity against the herpes viruses HSV-1 and HSV-2, including those Acyclovir-resistant, and human cytomegalovirus (HCMV) has been efficiently accomplished. The synthesis highlights a new pyridone approach that effectively combines a double, intramolecular Michael addition in a conjugated ester-conjugated amide with oxidation-decarboxylation of the resulting piperidone.
- Mekouar, Khalid,Genisson, Yves,Leue, Stefanie,Greene, Andrew E.
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p. 5212 - 5215
(2007/10/03)
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- Unprecedented adducts formed by camptothecin and mappicine ketone with maleic anhydride under microwave irradiation
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The Diels-Alder reaction of the naturally occurring alkaloids, camptothecin and mappicine ketone with maleic anhydride under microwave irradiation affords two unprecedented adducts.
- Das,Madhusudhan,Kashinatham
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p. 326 - 328
(2007/10/03)
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- A convergent total synthesis of mappicine ketone: A leading antiviral compound
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An efficient total synthesis of the naturally occuring mappicine ketone 1 and mappicine 2 are described. The approach is based on the assembly of tricyclic amine 5 with pseudo acid chloride 20. A Friedlander condensation is utilized for the construction o
- Yadav,Sarkar, Sanjita,Chandrasekhar
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p. 5449 - 5456
(2007/10/03)
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- Enantioselective synthesis of (S)- and (R)-mappicines and their analogues
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The naturally occurring alkaloids, camptothecin and mappicine ketone were converted to racemic mappicine acetate which was enantioselectively hydrolyzed to (S)- and (R)-mappicines in high optical purity using baker's yeast and a lipase, Amano PS. Treatment of the racemic acetate with baker's yeast afforded (S)-mappicine while with Amano PS yielded (R)-mappicine. 9- Methoxycamptothecin and 9-methoxymappicine ketone underwent similar conversion to (S)- and (R)-9-methxymappicines.
- Das, Biswanath,Madhusudhan
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p. 7875 - 7880
(2007/10/03)
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- Total synthesis of nothapodytine b and (-)-mappicine
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Concise total syntheses of naturally occurring nothapodytine B (1, mappicine ketone) and ( - )-mappicine (3) are detailed. The approach is based on the implememation of a room-temperature, inverse electron demand Diels-Alder reaction of the N-sulfonyl-1-aza-1.3-butadiene 11 for assemblage of a pyridone 1) ring precursor central to the structure. A Friedlander condensation is utilized for constructing the AB ring system of 1 and 3. An acid-catalyzed reaction sequence is used to accomplish a deprotection with subsequent ring-closure for introduction of the C ring in a single step.
- Boger, Dale L.,Hong, Jiyong
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p. 1218 - 1222
(2007/10/03)
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- Chemoenzymatic Transformation of the Natural Antitumour Alkaloid 20-O-Acetylcamptothecin to Mappicine Ketone and (S)-Mappicine
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Microwave irradiation of the naturally occurring antitumour alkaloid 20-O-acetylcamptothecin affords trans- and cis-Δ19,20-20-O-acetylmappicine and 17-acetylmappicine ketone. The first two products when treated with dilute alkali yield mappicine ketone, an antiviral lead compound, which is reduced with baker's yeast to form another natural alkaloid, (S)-mappicine. Baker's yeast treatment of the major product, trans-Δ19,20-20-O-acetylmappicine produces both mappicine ketone as well as (S)-mappicine. The last compound is converted to mappicine ketone by oxidation with pyridinium chlorochromate.
- Das, Biswanath,Madhusudhan,Venkataiah
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p. 662 - 665
(2007/10/03)
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- The first conversion of camptothecin to (S)-mappicine by an efficient chemoenzymatic method
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Camptothecin has been converted for the first time to (S)-mappicine via mappicine ketone, which is the sole product of the microwave irradiation of camptothecin. Baker's yeast reduction of mappicine ketone yielded (S)- mappicine in high optical purity.
- Das, Biswanath,Madhusudhan,Kashinatham
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p. 1403 - 1406
(2007/10/03)
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- Synthesis of (S)-Mappicine and mappicine ketone via radical cascade reaction of isonitriles
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(S)-Mappicine (2) and mappicine ketone (1) have been prepared from methylacetoacetate (4) by a strategy featuring a radical cascade reaction of an isonitrile as the key step. The introduction of the hydroxy group of (S)- mappicine occurred with moderate selectivity through asymmetric hydroxylation.
- Josien, Hubert,Curran, Dennis P.
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p. 8881 - 8886
(2007/10/03)
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- Method for making certain pyrano[3',4':6,7]indolizino-[1,2-B]quinolinones
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A method for making 8-methyl-7-(1-oxopropyl)indolizino[1,2-b]quinolin-9(11H)-ones from 4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-3,14(4H,12H)-diones, said method being graphically illustrated as follows: STR1
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- Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity
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Several camptothecin derivatives containing a modified hydroxy lactone ring have been synthesized and evaluated for inhibition of topoisomerase I and cytotoxicity to mammalian cells. Each of the groups of the hydroxy lactone moiety, the carbonyl oxygen, the ring lactone oxygen, and the 20-hydroxy group, were shown to be critical for enzyme inhibition. For example the lactol, lactam, thiolactone, and 20-deoxy derivatives did not stabilize the covalent DNA-topoisomerase I complex. With a few exceptions, those compounds that did not inhibit topoisomerase I were not cytotoxic to mammalian cells. Two cytotoxic derivatives that did not inhibit topoisomerase I were shown to produce non-protein-associated DNA single-strand breaks and are likely to have a different mechanism of action. One of these compounds was tested for antitumor activity and was found to be inactive. The present findings, as well as other reports that the hydroxy lactone ring of camptothecin is critical for antitumor activity in vivo, correlate with the structure-activity relationships at the level of topoisomerase I and support the hypothesis that antitumor activiy is related to inhibition of this target enzyme.
- Hertzberg,Caranfa,Holden,Jakas,Gallagher,Mattern,Mong,Bartus,Johnson,Kingsbury
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p. 715 - 720
(2007/10/02)
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