The Preparation of 4,5-Dihydro-3-Aryl-Naphth-[1,2-c]- Isoxazoles From Dilithiated 1-Tetralone Oxime and Aromatic Esters

(20S,2′′S)-20-[4′-(3′′-Hydroxy-2′′-methylpropyl)-3′-methylisoxazol-5-yl]-5β-pregnan-3β,16β-diol

“…The title compound was synthesized readily starting from 23-acetylsarsasapogenin (Meza-Reyes et al, 2005) in a one-pot reaction carried out in dry media (see Experimental). This new route improves known procedures, which make necessary the isolation of an oxime intermediate, prior to the heterocyclization in acid conditions (Beam et al, 2000). Full details about the involved chemistry and mechanistic aspects of this unprecedented reaction will be reported elsewhere.…”

“…For a general introduction to steroids functionalized with heterocycles, see: Banday et al (2008); Pathak & Jindal (1998); Litvinovskaya et al (1998); Beam et al (2000). For the biological activity of danazol, a steroid sharing structural features with the title compound, see: Gupta et al (1999).…”

Identification of Tricyclic Agonists of Sphingosine-1-phosphate Receptor 1 (S1P1) Employing Ligand-Based Drug Design

“…Schemes – outline the synthesis of representative examples of compounds with variations to the phenyl ring, central ring, heterocyclic ring, the lipophilic tail piece, and the polar head piece . The key step in the synthesis of the bis-isoxazole 10 (Scheme ) is the condensation of dilithiated 1-tetralone oxime with methyl 3-phenyl-4-(trifluoromethyl)­isoxazole-5-carboxylate . For optimal yields, LiTMP was the base of choice to affect this condensation; LDA or n -BuLi gave poor yields.…”

“…7-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-3a,4-dihydro-3H-chromeno-[4,3-c]isoxazol-3-ol (19). To a homogeneous solution of 4-(7-(2,2dimethyl-1,3-dioxolan-4-yl)-2H-chromen-4-yl)morpholine (0.266 g, 0.838 mmol) and triethylamine (0.232 mL, 1.68 mmol) in anhydrous acetonitrile (3.0 mL) at 0 °C was added a solution of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride 16 (0.217 g, 0.838 mmol) in acetonitrile (1.0 mL).…”

“…18 The key step in the synthesis of the bis-isoxazole 10 (Scheme 1) is the condensation of dilithiated 1-tetralone oxime with methyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate. 19 For optimal yields, LiTMP was the base of choice to affect this condensation; LDA or n-BuLi gave poor yields. In the case of the tricyclic chroman (24), the tetralone oxime route led to intractable mixtures of products during the condensation step.…”