Scaffold hopping of sampangine: Discovery of potent antifungal lead compound against Aspergillus fumigatus and Cryptococcus neoformans

One‐Pot Generation of Benzynes from Phenols: Formation of Primary Anilines by the Deoxyamination of Phenols

“…Anhydrous 1,4-dioxane, 1,2-dimethoxyethane, and toluene were purchased from FUJIFILM Wako Pure Chemical. 2-(Phenylethynyl)phenol (2q), [19] N-(2-hydroxyphenyl)phthalimide (2u), [20] 2-(trimethylsilyl)phenol (2v), [6g] 7-hydroxybenzofuran (2w), [21] 7-hydroxy-1-methylindole (2x), [11] 4-cyanophenyl nonaflate (4i), [22] 3,5-dimethoxyphenyl triflate (4a'), [23] 3,5-dimethoxyphenyl tosylate (4a''), [24] and 3,5-dimethoxyphenyl mesylate (4a''') [24] were prepared according to the reported procedures. All other reagents were purchased from FUJIFILM Wako Pure Chemical, To kyo Chemical Industry, Sigma-Aldrich, Nacalai tesque, Kishida Chemical, Matrix Scientific or Combi-Blocks and used without further purification.…”

“…The crude product, in which 2-(3-amino-2-(trimethylsilyl)phenyl)phthalimide, 2-(2-amino-3-(trimethylsilyl)phenyl)phthalimide, and 2-(2-aminophenyl)phthalimide were not detected by 400 MHz 1 HNMR analysis, was purified by column chromatography on silica gel (hexane/ EtOAc = 2:1) to provide the title compound Table 3, entry 12): [41] By following the General Procedure, am ixture of KHMDS (0.60 mL, 0.60 mmol), NfF (43 mL, 0.24 mmol), tris(trimethylsilyl)amine (93 mg, 0.40 mmol) and 2-(trimethylsilyl)phenol (2v) 6f (28 mg, 0.20 mmol) was stirred in THF (2.0 mL) for 5h at 60 8C. The crude product, in which 2,3bis(trimethysilyl)aniline, 2,6-bis(trimethysilyl)aniline, and 2-(trimethysilyl)aniline were not detected by 400 MHz 1 HNMR analysis, was purified by column chromatography on silica gel (hexane/ EtOAc = 2:1) to provide the title compound Table 3, entry 13): [42] By following the General Procedure, am ixture of KHMDS (0.60 mL, 0.60 mmol), NfF (43 mL, 0.24 mmol), tris(trimethylsilyl)amine (93 mg, 0.40 mmol) and 7-hydroxybenzofuran (2w) [21] (27 mg, 0.20 mmol) was stirred in THF (2.0 mL) for 5hat 60 8C. The crude product, in which 7-aminobenzofuran, 6-amino-7-(trimethylsilyl)benzofuran, and 7-amino-6-(trimethylsilyl)benzofuran were not detected by 300 MHz 1 HNMR analysis, was purified by column chromatography on silica gel (hexane/EtOAc = 2:1) to provide the title compound 3p 6-Amino-1-methylindole (3 q) ( Table 3, entry 14): [43] By following the General Procedure, am ixture of KHMDS (0.60 mL, 0.60 mmol), NfF (43 mL, 0.24 mmol), tris(trimethylsilyl)amine (93 mg, 0.40 mmol) and 7-hydroxy-1-methylindol (2x) [11] (29 mg, 0.20 mmol) was stirred in THF (2.0 mL) for 5hat 60 8C.…”

“…1 HNMR (300 MHz, CDCl 3 ): d = 0.28 (s, 9H), 6.68 (dd, J = 8.0, 1.0 Hz, 1H), 6.93 (ddd, J = 7.5, 7.5, 1.0 Hz, 1H), 7.27 (ddd, J = 8.0, 7.5, 2.0 Hz, 1H), 7.37 ppm (dd, J = 7.5, 2.0 Hz, 1H). 7-Hydroxybenzofuran (2 w) ( Table 3, entry 13): [21] An oven-dried round-bottom flask was charged with 7-methoxybenzofuran (0.20 g, 1.4 mmol) and as tir-bar.T he flask was equipped with a three-way stopcock, and evacuated and back-filled with nitrogen (this process was repeated three times). CH 2 Cl 2 (14 mL) was added into the flask by using asyringe.…”

Oxoisoaporphines and Aporphines: Versatile Molecules with Anticancer Effects

“…We review some of the several studies on the structure of the units for Tetrahymena thermophila (tt), Tribolium castaneum (tc), or Oryzias latipes (ol) [25,26,116,117]. In the case of human telomerase, crystal structures of hTERT and hTR have not yet been reported; consequently, the molecular docking studies are based in non-humans [118,119]. The electron microscopy (EM) structure shows that the TERT unit allows an open and closed configuration for human telomerase, which in Tribolium castaneum is mediated by interactions between the RNA-binding domain (TRBD) and the thumb (two terminal domains of tcTERT), and is possibly required for telomerase ribonucleoprotein (RNP) assembly [25].…”

A complex game of hide and seek: the search for new antifungals

“…114, 115 Sheng and co-workers utilized scaffold hopping and structural simplification strategies to generate analogues of sampangine with improved antifungal activity as well as drug-like properties. 116, 117 The aqueous, methanolic, and acetone extracts of three plants ( Combretum caffrum (bushwillow tree), Salix capensis Thunb (cape silver willow), and Schotia latifolia Jacq. (a legume)) used for the treatment of livestock disease in South Africa were examined for antimycotic activity.…”