Reagent‐Controlled Cyclization–Deprotection Reaction to Yield either Fluorenes or Benzochromenes

Killander, Dan; Sterner, Olov

doi:10.1002/ejoc.201402722

Cited by 11 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 However, instead of benzochromenes-triazoles 14a-14c, new 9H-fluorenes-1,2,3-triazoles 10a-10c were obtained with yields ranging from 25 to 40%, by Friedel-Crafts alkylation (Scheme 3). Similar results have been reported in the literature 26,27 using Lewis acid. The characterization of the 9H-fluorenes-1,2,3-triazoles was performed by IR, 1 H and 13 C NMR.…”

Section: Synthesis Of α-Hidroxy-123 Triazolessupporting

confidence: 92%

New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: Synthesis and Evaluation as Glycine Transporter 1 Inhibitors

Silva¹,

Silva²,

Neto³

et al. 2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Section: Synthesis Of α-Hidroxy-123 Triazolessupporting

confidence: 92%

New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: Synthesis and Evaluation as Glycine Transporter 1 Inhibitors

Silva¹,

Silva²,

Neto³

et al. 2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

“…Several synthetic strategies to prepare benzo[ c ]chromenes have been reported in the literature [ 18 , 19 ]. However, as the focus in this study is on the benzyl alcohol functionality of 1 , we essentially relied on the synthetic manipulation of pulchrol ( 1 ) itself.…”

Section: Resultsmentioning

confidence: 99%

SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality

et al. 2020

Self Cite

View full text Add to dashboard Cite

Pulchrol (1) is a natural benzochromene isolated from the roots of Bourreria pulchra, shown to possess potent antiparasitic activity towards both Leishmania and Trypanozoma species. As it is not understood which molecular features of 1 are important for the antiparasitic activity, several analogues were synthesized and assayed. The ultimate goal is to understand the structure–activity relationships (SAR:s) and create a QSAR model that can be used for the development of clinically useful antiparasitic agents. In this study, we have synthesized 25 2-methoxy-6,6-dimethyl-6H-benzo[c]chromen analogues of 1 and its co-metabolite pulchral (5a), by semi-synthetic procedures starting from the natural product pulchrol (1) itself. All 27 compounds, including the two natural products 1 and 5a, were subsequently assayed in vitro for antiparasitic activity against Trypanozoma cruzi, Leishmania brasiliensis and Leishmania amazoniensis. In addition, the cytotoxicity in RAW cells was assayed, and a selectivity index (SI) for each compound and each parasite was calculated. Several compounds are more potent or equi-potent compared with the positive controls Benznidazole (Trypanozoma) and Miltefosine (Leishmania). The compounds with the highest potencies as well as SI-values are esters of 1 with various carboxylic acids.

show abstract

“…Pulchrol ( 1 ) was found to possess antiparasitic activity against Leishmania braziliensis , L. amazonensis , L. mexicana and Trypanosoma cruzi [ 22 , 25 ]. A synthetic route was developed in 2014 [ 26 , 27 ], and recently we reported the effects that transformations of its A-ring benzyl alcohol functionality have against T. cruzi epimastigotes, L. amazonensis promastigotes and L. braziliensis promastigotes, as well as their cytotoxicity towards mammalian cells (assayed in RAW cells) [ 28 ]. We are now interested to expand the previous study [ 28 ] with compounds having various substituents in the B- and C-rings.…”

Section: Introductionmentioning

confidence: 99%

SARs for the Antiparasitic Plant Metabolite Pulchrol. Part 2: B- and C-Ring Substituents

et al. 2020

Self Cite

View full text Add to dashboard Cite

Neglected tropical diseases affect most of the underprivileged populations in tropical countries. Among these are chagas and leishmaniasis, present mainly in South and Central America, Africa and East Asia. Current treatments are long and have severe adverse effects, therefore there is a strong need to develop alternatives. In this study, we base our research on the plant metabolite pulchrol, a natural benzochromene which has been shown to possess antiparasitic activity against Trypanosoma and Leishmania species. In a recent study, we investigated how changes in the benzyl alcohol functionality affected the antiparasitic activity, but the importance of B- and C-ring substituents is not understood. Fifteen derivatives of pulchrol with different substituents in positions 1, 2, 3, and 6 while leaving the A-ring intact, were therefore prepared by total synthesis, assayed, and compared with pulchrol and positive controls. The generated series and parental molecule were tested in vitro for antiparasitic activity against Trypanosoma cruzi, Leishmania braziliensis, and L. amazonensis, and cytotoxicity using RAW cells. Substantial differences in the activity of the compounds synthesized were observed, of which some were more potent towards Trypanosoma cruzi than the positive control benznidazole. A general tendency is that alkyl substituents improve the potency, especially when positioned on C-2.

show abstract

Reagent‐Controlled Cyclization–Deprotection Reaction to Yield either Fluorenes or Benzochromenes

Cited by 11 publications

References 25 publications

New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: Synthesis and Evaluation as Glycine Transporter 1 Inhibitors

New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: Synthesis and Evaluation as Glycine Transporter 1 Inhibitors

SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality

SARs for the Antiparasitic Plant Metabolite Pulchrol. Part 2: B- and C-Ring Substituents

Contact Info

Product

Resources

About