Total synthesis of rac-longamide B

Sun, Xuetong; Chen, Austin

doi:10.1016/j.tetlet.2007.03.022

Cited by 25 publications

(7 citation statements)

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“…The preliminary structure-activity relationships deduced should encourage further studies aimed at investigating their mechanisms of action as well as at optimizing their antiprotozoal activities. The availability of tens of other natural bromopyrroles and the possibility of obtaining some non-natural derivatives through total synthesis (model total syntheses for dispacamide B [ 30 ] and longamide B [ 31 ] have been reported) could be particularly helpful to this aim.…”

Section: Discussionmentioning

confidence: 99%

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

et al. 2010

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In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.

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Section: Discussionmentioning

confidence: 99%

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

et al. 2010

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“…[36] In their synthesis of (+ +)-agelastatin A( 108), Trost and Dong used an annulative allylic alkylation sequence between mesodicarbonate 49 b and pyrrole 103 to assemble three of the four fused rings present in the target molecule (Scheme 23). [39] The same group later reported that this annulative allylic alkylation approach was also applicable to the synthesis of pyrazino[1,2-a]indoles,w hich are important structuresf rom am e-Scheme23. [37] In at estament to the versatility of annulative allylic alkylation reactions, Trost and Dong later showed that they could access the opposite enantiomer of agelastatin (ent-108)b y simply changing the nucleophile for the allylic substitution sequence.…”

Section: Scheme11 Semi-synthesis Of Glaucasterolmentioning

confidence: 99%

“…From 114,b romination of the pyrrole followed by oxidation of the primary alcoholt oi ts carboxylica cid completed the synthesisofl ongamide B( 115). [39] The same group later reported that this annulative allylic alkylation approach was also applicable to the synthesis of pyrazino[1,2-a]indoles,w hich are important structuresf rom am e-Scheme23. To talsynthesis of (+ +)-agelastatin A.…”

Section: Scheme22 Enantioselectivesynthesis Of Amedicinally Relevantmentioning

confidence: 99%

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Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

Trost

Kalnmals

2019

Chemistry A European J

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Metal-catalyzed allylic alkylation reactions between dual nucleophiles and dual electrophiles represent ap owerful set of methodsf or the synthesis of small-, medium-, and even large-sized rings. Using this strategy,ahandful of simple allylic diol derivatives can be transformed into a broad array of complexc arbo-and heterocycles of varying ring sizes in just as ingle step. Because of their ability to rapidly generate complexity, annulative allylic alkylationr eactions between dual nucleophiles and dual electrophiles have been extensively employed in the total synthesis of both naturalp roducts and pharmaceuticalcompounds.Scheme1.GeneralScheme for metal-catalyzed allylic alkylation.Scheme2.GeneralScheme for annulative allylic alkylation reactionsu sing a dual electrophile.Scheme3.Differenttypesofa nnulativeallylic alkylation reactions.Scheme4.GeneralScheme for allylic alkylation reactionsi nvolving 1,1-substitutions.

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“…The susccess of producing oroidin derivatives by several approach (Fresneda et al, 2001;Lindel and Hoffmann, 1997;Olofson et al, 1998;Sun and Chen, 2007;Ando et al, 2006) have offer more possibility of producing antiprotozoal compounds which are closely related to this compounds as described by Scala et al (2010) by a synthetic route. The synthesis of the oroidin itself has been reported in many literatures (as reviewed in Forte et al, 2009).…”

Section: Synthesis Approach: An Alternative For Continuous Supplymentioning

confidence: 99%

New Hope on Drug Leads Development From Deep Ocean: Halogenated Alkaloids of Agelas Sponges

Hertiani

2014

Indonesian J. Pharm.

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Agelas sponge is found in abundancy from Indonesia's ocean. This sponge produces an important chemotaxonomic group of compounds, derived from pyrrole-imidazole alkaloids. This group of compounds is one of those exclusively found from marine environment. Marine sponges are reported to be promising drug lead producers having unique chemical structures of which many have no terrestrial counterparts. The objective of this report is to give an overview of the reported attempts from up to down stream to develop pyrrole-imidazole alkaloids as new drug lead. Literatures up to 2013 reporting this group of compounds from Agelas sponges were studied. Discussion on the halogenated alkaloids covers the producers, description of high chemical diversity, identification, biosynthesis and ecological relevance as well as their role as a promising drug candidate. Alternatives to provide continous supplies for drug development are also discussed considering that wild harvesting of the sponge producers can lead to ecological damage in the future. Broad range of interesting pharmacological importance as well as several success in developing synthetic route for production supports its development as drug candidate.

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Total synthesis of rac-longamide B

Cited by 25 publications

References 10 publications

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

New Hope on Drug Leads Development From Deep Ocean: Halogenated Alkaloids of Agelas Sponges

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