Flavonoids. I. Synthesis of 2,2-Dialkyl-Δ<sup>3</sup>-isoflavenes from Coumarins<sup>1</sup>

Cook, Clarence; Corley, Robert C.; Wall, Monroe E.

doi:10.1021/jo01023a032

Cited by 26 publications

(10 citation statements)

References 1 publication

(1 reference statement)

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“…R f : 0.68 (UV visible and fluorescent) (ethyl acetate/hexane, 1:1); mp 230–232 °C (Lit. 74 mp 233–234 °C); 1 H NMR (400 MHz; DMSO- d 6 ) δ H : 2.60 (s, 3H, CH 3 ), 3.81 (s, 3H, OCH 3 ), 6.63 (dd, 1H, C 6 –H, J = 2.3, 8.9 Hz), 6.71 (d, 1H, C 8 –H, J = 2.3 Hz), 6.90 (d, 2H, Ph-2,6-H 2 , J = 8.6 Hz), 7.29 (d, 2H, Ph-3,5-H 2 , J = 8.6 Hz), 7.72 (d, 1H, C 5 –H, J = 8.9 Hz) and 12.42 (s, 1H, OH); MS (FAB + ) m / z : 283.2 [100, (M + H) + ]; MS (FAB – ) m / z : 281.2 [100, (M – H) − ]; Acc. MS (FAB + ): 283.0898, C 17 H 15 O 4 requires 283.0892; found C, 71.98; H, 5.36; C 17 H 14 O 4 requires C, 72.33; H, 5.00%.…”

Section: Methodsmentioning

confidence: 99%

C-3- and C-4-Substituted Bicyclic Coumarin Sulfamates as Potent Steroid Sulfatase Inhibitors

et al. 2018

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Synthetic routes to potent bicyclic nonsteroidal sulfamate-based active-site-directed inhibitors of the enzyme steroid sulfatase (STS), an emerging target in the treatment of postmenopausal hormone-dependent diseases, including breast cancer, are described. Sulfamate analogs 9–27 and 28–46 of the core in vivo active two-ring coumarin template, modified at the 4- and 3-positions, respectively, were synthesized to expand structure–activity relationships. α-Alkylacetoacetates were used to synthesize coumarin sulfamate derivatives with 3-position modifications, and the bicyclic ring of other parent coumarins was primarily constructed via the Pechmann synthesis of hydroxyl coumarins. Compounds were examined for STS inhibition in intact MCF-7 breast cancer cells and in placental microsomes. Low nanomolar potency STS inhibitors were achieved, and some were found to inhibit the enzyme in MCF-7 cells ca. 100–500 more potently than the parent 4-methylcoumarin-7-O-sulfamate 3, with the best compounds close in potency to the tricyclic clinical drug Irosustat. 3-Hexyl-4-methylcoumarin-7-O-sulfamate 29 and 3-benzyl-4-methylcoumarin-7-O-sulfamate 41 were particularly effective inhibitors with IC50 values of 0.68 and 1 nM in intact MCF-7 cells and 8 and 32 nM for placental microsomal STS, respectively. They were docked into the STS active site for comparison with estrone 3-O-sulfamate and Irosustat, showing their sulfamate group close to the catalytic hydrated formylglycine residue and their pendant group lying between the hydrophobic sidechains of L103, F178, and F488. Such highly potent STS inhibitors expand the structure–activity relationship for these coumarin sulfamate-based agents that possess therapeutic potential and may be worthy of further development.

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Section: Methodsmentioning

confidence: 99%

C-3- and C-4-Substituted Bicyclic Coumarin Sulfamates as Potent Steroid Sulfatase Inhibitors

et al. 2018

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“…a mixture of ester (10)(11)(12) and KOH (1.5 g) in pyridine (15 ml) was kept for (2 h) at room temperature. The resulting white solid was filtered and washed with water and crystallized from ethanol, Table (1,2).…”

Section: -Hydroxy Coumarins (13-15)mentioning

confidence: 99%

“…Esters (4-6) were cyclized in pyridine / potassium hydroxide to the (7-9) (Scheme 1), compound (7) show absorption at  max cm -1 3015 (Ar-H), 1708 (C=O). 3-Phenyl-4-hydroxy coumarins (13)(14)(15), were synthesized from substituted methyl salicylate which was treated with phenyl acetic acid in pyridine and phosphorous oxychloride to give the esters (10)(11)(12), compound (10) show absorption at  cm -1 at 3032 (Ar-H) and 1710 (C=O), the resultant compounds were cyclized to the final products (13)(14)(15) by their reaction with potassium hydroxide in pyridine, compound (13) show absorption  cm -1 at 3300 (OH), 3020 (Ar-H), 1690 (C=O) and 1632 (C=C) (Scheme 2). Physical and spectral data listed in Tables (1,2).…”

Section: -Hydroxy Coumarins (13-15)mentioning

confidence: 99%

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Synthesis of 3-phenyl-4-styryl and 3-phenyl-4-hydroxy coumarins

Ismmaeel¹

2008

J.Edu.Sci.

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“…As is known, anhydrous hydrogen fluoride is capable of regenerating carbocations from unsaturated compounds [4]. The rather low boiling temperature of hydrogen fluoride (19.5~ allows it to be readily removed from the mixture upon reaction.…”

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confidence: 99%