Bioactive Furanonaphthoquinones from Crescentia cujete

Heltzel, Carl E.; Gunatilaka, A. A. Leslie; Glass, Thomas E.; Kingston, David G. I.; Hoffmann, Glenn; Johnson, Randall K.

doi:10.1021/np50099a008

Cited by 56 publications

(34 citation statements)

References 6 publications

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“…Especially 1 H-NMR and 13 C-NMR assingnments of rac-1 were established by heteronuclear multiple bond connectivity (HMBC) correlations and were listed in Experimental.…”

Section: Resultsmentioning

confidence: 99%

“…12,13) Perusal of these reports prompted us to carry out the epoxidation of 3 with the Shi catalyst and Oxone in buffered media. 1,14) We obtained (R)-2 in good chemical yield with modest enantioselectivity (40% ee) (Chart 2).…”

Section: Resultsmentioning

confidence: 99%

“…Chemical shifts are recorded in parts per million (ppm) relative to TMS. 13 C-NMR spectra were proton decoupled and recorded on a JEOL JNM-ECP400 or JNM-ECP500 spectrometers using the carbon signal of the deuterated solvent as the internal standard. IR spectra were recorded in KBr using a PERKIN ELMER SPECTRUM 2000FT-IR spectrometer.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of Biologically Active (-)-Dehydroiso-.BETA.-lapachone and the Determination of Its Absolute Configuration

Kimachi

Torii

Kobayashi

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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NoteWe recently reported the total synthesis of two biologically active natural products, Rhinacanthin A and Rhinacanthin C. 1,2) In the synthesis of both compounds, we accomplished highly regioselective and stereoselective construction of alapachone or 1,4-naphthoquinone structures using 2-alkoxy-1,4-dimethoxynapthalenes, which we refer to as reduced naphthoquinone equivalents.1) In the continuous study on the synthesis and evaluation of novel biologically active natural products, we describe herein the convenient and selective synthesis of racemic dehydroiso-b-lapachone and the asymmetric synthesis of (Ϫ)-dehydroiso-b-lapachone (1), which we also establishes the absolute configuration as (R).(Ϫ)-Dehydroiso-b-lapachone (1), which racemic structure has been constructed and confirmed by the chemical modification of naturally occurring Lomatiol isolated from Lomatia ilicifolia and Lomatia longifolia in 18953) and has been reinvestigated by Hooker in 1936, 4) recently isolated from extracts of the rainforest plants, Lantana involucrata, shows significant in vitro cytotoxic activity against various human tumor cell lines. (Fig. 1) 5) The non-selective synthesis of racemic dehydroiso-b-lapachone (rac-1) 6) has been reported but its absolute configuration has not been established to date. Regarding the recent studies on the synthesis of 1,2-furanonaphthoquinones, Kongkathip et al. showed the acid catalyzed cyclization of 2-substituted-1,4-naphthoquinones affords various furano-or pyranonaphthoquinones in moderate to good yield. 7) Most recently, Singh et al. reported the chemical transformation of lapachol to its related derivatives including dehydroiso-b-lapachone. 8) In this study, Singh reported that the treatment of lapachol with nitrous acid afforded rac-1 with equal amounts of three other isomers.Inspired by these results, we first undertook the selective synthesis of racemic dehydroiso-b-lapachone (rac-1), which gave us knowledge to undertake the asymmetric synthesis of this natural product. As for the synthetic strategy, we envisaged a 1,2-furanonaphthoquinone formation by the ringopening reaction of the epoxynaphthlene (2) and the subsequent oxidative ring closure to obtain rac-1. (Fig. 2). Key words synthesis; naphthoquinone; dehydroiso-b-lapachone; anti tumor activity; 2-alkoxy-1,4-dimethoxynaphthalene Chem. Pharm. Bull. 59(6) 753-756 (2011) © 2011 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: tkimachi@mukogawa-u.ac.jp Synthesis of Biologically

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“…Especially 1 H-NMR and 13 C-NMR assingnments of rac-1 were established by heteronuclear multiple bond connectivity (HMBC) correlations and were listed in Experimental.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Synthesis of Biologically Active (-)-Dehydroiso-.BETA.-lapachone and the Determination of Its Absolute Configuration

Kimachi

Torii

Kobayashi

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…In addition, scopoletin 15 and esculatin 16 were found in nature and they have antiproliferative, antioxidant, and anti-inflammatory activities ( Figure 1). Dihydrofurocoumarins such as fercoprolone, 17 mutisicoumarin, 18 cyclobrachycoumarin, 19 and isoerlengefusciol 20 have been found in nature and they have similar activities to coumarin derivatives. We have also recently reported that some 3-cyano-4,5-dihydrofurans show antifungal and antibacterial activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antifungal activity of new dihydrofurocoumarins and dihydrofuroquinolines

Ustalar¹,

Yılmaz²,

Osmani³

et al. 2017

Turk J Chem

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“…Some dehydroiso-α-lapachones 1a,b,b',f, having a 2-isopropenyl-2,3-dihydronaphtho- [2,3-b]furan-4,9-dione structure, were isolated from Cresentia cujete, and showed interesting mutagenic activities [2]. In this paper, one-step preparation of 2-isopropenyl-2,3-dihydronaphtho [2,3-b]furan-4,9-diones 1 are described.…”

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confidence: 99%

One‐step preparation of some 2‐isopropenyl‐2,3‐dihydronaphtho‐[2,3‐b]furan‐4,9‐diones

Yamaguchi

Katsuki

Yokoyama

et al. 2001

Journal of Heterocyclic Chem

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Some 2-isopropenyl-2,3-dihydronaphtho [2,3-b]furan-4,9-diones 1a-f,b',f' were prepared by one-step cyclizations of 2-hydroxy-1,4-naphthoquinones 2a-f with 1,4-dibromo-2-methyl-2-butene (3).J. Heterocyclic Chem., 38, 511 (2001).Our recent interests were focused on the effective preparation of natural 2-isopropenyl-2,3-dihydrobenzofuran derivatives [1]. Some dehydroiso-α-lapachones 1a,b,b',f, having a 2-isopropenyl-2,3-dihydronaphtho- [2,3-b]furan-4,9-dione structure, were isolated from Cresentia cujete, and showed interesting mutagenic activities [2]. In this paper, one-step preparation of 2-isopropenyl-2,3-dihydronaphtho [2,3-b]furan-4,9-diones 1 are described.Nickl reported the first one-step preparation of 2-isopropenyl-2,3-dihydrobenzofuran derivatives; cyclization of 2',4',6'-trihydroxyacetophenone with 1,4-dibromo-2-methyl-2-butene 3 effectively gave 7-acetyl-2-isopropenyl-2,3-dihydrobenzofuran-4,6-diol in ethanol/sodium ethoxide solution [3]. But, the similar cyclization of general phenols with 3 generates only O-alkylation products in ethanol/sodium ethoxide solution. We found that the cyclization of general phenols with 3 was effective in non-polar solvents, such as ether or toluene with sodium metal or sodium hydride [1], and the cyclization of 1,3-diketones with 3 was effective in acetone with potassium carbonate [4].For the preparation of 1, a one-step cyclization of 2-hydroxy-1,4-naphthoquinones 2 with 3 was planned. The one-step cyclization was studied under several conditions using commercially available 2-hydroxy-1,4-naphthoquinone (2a), and the results are summarized in table 1. Cyclization of 2a with 3 gives none of the cyclized product in polar conditions, such as ethanol/sodium ethoxide or acetone/potassium carbonate, but gives the desired cyclized product 1a under non-polar conditions. Cyclizations using sodium hydride (2 equivalents) in refluxing ether or tetrahydrofuran, calcium hydride (2 equivalents) in refluxing toluene, and n-butyl lithium (1 equivalent) in refluxing toluene, show low yields (<4%). But, cyclization using sodium hydride (2 equivalents) in refluxing toluene shows the best yield of 16% after 24 hours. Use of equal (1 equivalent) or excess ( 3 equivalents) amounts of sodium hydride decreases the yields (1 equivalent gives 0%, 3 equivalents give 1%), and longer reaction time also decreases the yield (48 hours gives < 1%).For a preparation of the corresponding 2-hydroxy-1,4-naphthoquinones 1b-f, five methoxy-substituted 2-hydroxy-1,4-naphthoquinones 2b-f were prepared according to reported procedures [5a-e]. Four methoxysubstituted 2-hydroxy-1,4-naphthoquinones (2b-e) and

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Bioactive Furanonaphthoquinones from Crescentia cujete

Cited by 56 publications

References 6 publications

Synthesis of Biologically Active (-)-Dehydroiso-.BETA.-lapachone and the Determination of Its Absolute Configuration

Synthesis of Biologically Active (-)-Dehydroiso-.BETA.-lapachone and the Determination of Its Absolute Configuration

Synthesis and antifungal activity of new dihydrofurocoumarins and dihydrofuroquinolines

One‐step preparation of some 2‐isopropenyl‐2,3‐dihydronaphtho‐[2,3‐b]furan‐4,9‐diones

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