Total Synthesis of the Antitumor Antibiotic Basidalin

Acosta, Jaime A. M.; Muddala, Ramesh; Barbosa, Luiz C. A.; Boukouvalas, John

doi:10.1021/acs.joc.6b01255

Cited by 21 publications

(8 citation statements)

References 39 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to generate tetronamide analogues of rubrolides, we explored the dehydration of aldol adducts 9 to the corresponding γ‐benzylidenetetronamides 10 . For this purpose, compound 9a was initially treated with pyridine as base and MsCl as a pro‐leaving group, following a procedure recently reported for the synthesis of the natural antitumor‐antibiotic basidalin . Under these conditions the starting material was totally consumed, but the desired product could not be isolated (Table , entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…) is a key structural feature of an increasing number of bioactive molecules, nearly all of them being of synthetic origin. In fact, the only tetronamide known to occur in nature is basidalin ( 2 ), an antitumor antibiotic isolated from terrestrial fungi . Synthetic tetronamides are frequently used as building blocks for the construction of complex molecules, as well as in chemical, medicinal and agrochemical research .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Acosta

Karak

Barbosa

et al. 2019

Pest Management Science

Self Cite

View full text Add to dashboard Cite

BACKGROUND: The increasing frequency and intensity of cyanobacterial blooms pose a serious threat to aquatic ecosystems. These blooms produce potent toxins that can contaminate drinking water and endanger the life of wild and domestic animals as well as humans. Consequently, the development of effective methods for their control is a matter of high priority. We have previously shown that some -benzylidenebutenolides, related to the rubrolide family of natural products, are capable of inhibiting the photosynthetic electron transport chain (Hill reaction), a target of commercial herbicides. Here we report the synthesis and biological properties of a new class of rubrolide-inspired molecules featuring a tetronamide motif.RESULTS: A total of 47 N-aryl tetronamides, including 38 aldol adducts, were prepared bearing phenyl, biphenyl, naphthyl, aliphatic and heteroaromatic groups. Some of the aldol adducts were dehydrated to the corresponding -benzylidenetetronamides, although satisfactory yields were obtained in only three cases (52-97%). None of the synthesized compounds were capable of blocking the Hill reaction. This notwithstanding, several aldol adducts equipped with a biphenyl substituent displayed excellent inhibitory activity against Synechococcus elongatus and other cyanobacterial strains (IC 50 = 1-5 M). Further, these tetronamides were found to be essentially inactive against eukaryotic microorganisms. CONCLUSION: Several newly synthesized biphenyl-containing tetronamides were shown to display potent and selective inhibitory activity against cyanobacteria. These compounds appear to exert their biological effects without interfering with the Hill reaction. As such, they represent novel leads in the search of environmentally benign agents for controlling cyanobacterial blooms.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Acosta

Karak

Barbosa

et al. 2019

Pest Management Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Five or six‐membered lactones (butenolides, pyrones) bearing a nitrogen‐containing unit are important heterocyclic ring systems, which can be present in several natural products and have a diverse range of biological properties. As shown in Figure , the natural compound Basidalin A is a novel butenolide bearing an amino group at position 4, which seems to have good antitumor activity against leukemia The Uncinine B , which is based on a combination of the pyrrolidinone and γ‐alkylidenebutenolide fragments, exhibits cytotoxicity against the Hep G2 cell line (IC50 6.1 µg/mL) . The synthetic γ‐alkylidenebutenolide C displays an antibacterial activity with a minimum inhibitory concentration (MIC) value of 20 µ g/mL against Escherichia coli while γ‐alkylidenebutenolide D exhibits cytotoxic activity against Ec9706 cells .…”

Section: Introductionmentioning

confidence: 99%

Tandem One‐Pot Approach to N‐Substituted Lactones by Carbon–Carbon Coupling Followed by 5‐exo‐dig or 6‐endo‐dig Cyclization: DFT Studies and Cyclization Mode

et al. 2019

View full text Add to dashboard Cite

A one‐pot approach has been developed for the preparation of a five or six‐membered ring of unsaturated lactones bearing an amino group through a tandem coupling oxacyclization reaction. This tandem process involves Sonogashira‐like cross‐coupling followed by 5‐exo‐dig or 6‐endo‐dig intramolecular oxacyclization, according to the nature of the alkynes substituent. Furthermore, DFT calculations were performed to analyze the origin of this regioselectivity of cyclization.

show abstract

“…Compounds containing the 4-aminofuran-2(5 H )-one scaffold, commonly known as tetronamides (Figure , I ), include the natural product basidalin ( III ) − and various synthetic molecules − (e.g., II and IV ), which are considered important templates for the development of agrochemicals , and pharmaceuticals − Because of the diverse biological properties of tetronamides, extensive studies of the synthesis of both chiral and achiral derivatives of such compounds have been conducted in recent years. − …”

Section: Introductionmentioning

confidence: 99%

Substituent-Modulated Conformation and Supramolecular Assembly of Tetronamides

Karak

Acosta

Barbosa

et al. 2016

Crystal Growth & Design

Self Cite

View full text Add to dashboard Cite

The crystal structures of nine compounds (1−9) bearing the 4-aminofuran-2(5H)-one scaffold (commonly known as tetronamide, C 4 H 5 NO 2) and two decorating aromatic/ heteroaromatic moieties with two stereocenters have been determined. Tetronamides bearing at the 5-position a phenyl moiety (1 and 2, 3-chloro derivatives with either a 4-p-tolylamino or 4-p-bromophenylamino substituent), an o-bromopyridyl moiety (3, a 3-bromo-4-p-tolylamino derivative), or an o-tolyl moiety (4, a 3-bromo-4-p-tolylamino derivative) adopt a U-shaped conformation. This conformation is stabilized by an intramolecular contact involving either the phenyl o-CH moiety (1 and 2) or the substituent at the ortho position (3 and 4) and the π system of the N-phenyl ring. The other five tetronamides (5−9) are not present with such an intramolecular contact. In fact, these last five compounds are not U-shaped and feature the presence at the 5-position of a p-biphenyl moiety (5 and 7, 3-bromo-4-p-tolylamino diastereomers differing as 5R and 5S), a p-methoxyphenyl moiety (6, a 3-chloro-4-pbromophenylamino derivative), or a 5-chlorofuran-2-yl moiety (8 and 9, 3-chloro-4-p-tolylamino diastereomers differing as 5R and 5S). Crystal structures of a 5,5-disubstituted tetronamide bearing m-nitrophenyl moieties (10) and a parent tetronamide without a substituent at the 5-position (11d) reinforce the conformational trend found in 1−9. Furthermore, OH•••O centrosymmetric dimers are formed only in the crystal structures of the U-shaped tetronamides. Chain motifs assembled through OH•••O and NH•••O hydrogen bonds are preferred in the line-shaped tetronamides. Furthermore, the conformer energies were calculated in both the gas and solution phases (B3LYP/6-31G*). The lowest-energy conformations feature an intramolecular N−H•••O hydrogen bond as in the crystal structure of 7. In the U-shaped tetronamides, the crystal structure conformations are similar to the third or fourth energetically ranked stable calculated conformer. Therefore, it is concluded that the substitution pattern in the U-shaped tetronamides allows for accessible secondary minimum-energy conformations that are easily adopted in the crystal structure as a result of their compatibility with the robust centrosymmetric O−H•••O dimer formation.

show abstract

Total Synthesis of the Antitumor Antibiotic Basidalin

Cited by 21 publications

References 39 publications

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Tandem One‐Pot Approach to N‐Substituted Lactones by Carbon–Carbon Coupling Followed by 5‐exo‐dig or 6‐endo‐dig Cyclization: DFT Studies and Cyclization Mode

Substituent-Modulated Conformation and Supramolecular Assembly of Tetronamides

Contact Info

Product

Resources

About