Preparation and crystal structures of two 3‐anthracenyl isoxazolyl sulfonamides

Abstract

1. base/THF, -78 o C 2. oxaziridine 6 or 7, -78 o C Lateral metalation and oxidation of 3-(9'-anthryl)-isoxazoles (1), using Davis' oxaziridine (6), produced the desired hydroxylation (2), along with sulfonamide adduct (3), and in the case of the use of butyl lithium as base, butyl addition products (4) and (5). Structures of isoxazole sulfonamides (3a) and (5a), were obtained as the SR/RS-diastereomer, however, studies indicate that this is a consequence of the crystallization process. Metalation studies with isoxazole (8) demonstrate that hydroxylation (9), can be carried out cleanly, minimizing formation of (10), using camphorsulfonyloxaziridine (7) as an electrophile.

Ethyl 3-(10-bromoanthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxylate

“…To more accurately inform our G-4 -small molecule docking studies, we rely on crystallographic determinations of AIMs. In previous studies we have determined that the dihedral angle between the isoxazole and the C-3 aryl is approximately orthogonal (Mosher et al, 1996;Li et al, 2008), and we have postulated that this is a critical feature in the biological activity of the AIMs. The anthracenyl group is almost perpendicular to the isoxazole plane in ethyl 3-(10′-chloroanthracenyl)-5-(1′′-phenyl-2′′-hydroxylethylenyl)isoxazole-4carboxylate [85.51 (4)°] (Li et al, 2006), which is similar to analogous anthracenyl isoxazole structures in the Cambridge Structural Database, i.e.…”

“…For the synthesis of anthryl isoxazoles, see: Mosher & Natale (1995); Zhou et al (1997); Han & Natale (2001); Rider et al (2010); Mirzaei et al (2012). For related structures, see: Mosher et al (1996); Han et al (2002Han et al ( , 2003; Li et al (2006Li et al ( , 2008. For the antitumor activity of aryl isoxazole amides (AIMs), see: Han et al (2009); Gajewski et al (2009); Balasubramanian et al (2011); Neidle (2012); Kohn et al (2012); Shoemaker (2006).…”

Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

“…The dihedral angle between the tricyclic planar aromatic moiety and the isoxazole from our crystallographic studies of intermediates and analogs, is in the range of 74 – 80° 22, 26–8,44,45. The idealized helical pitch angle for B-DNA was estimated to be ca .…”

Ethyl 3-(9-chloro-10-oxo-9,10-dihydroanthracen-9-yl)-5-methylisoxazole-4-carboxylate

“…For the synthesis of anthryl isoxazoles, see: Mosher & Natale (1995); Zhou et al (1997); Han & Natale, (2001); Rider et al (2010); Mirzaei et al (2012). For previous studies on anthryl isoxazole crystallography, see: Mosher et al (1996); Han et al (2002Han et al ( , 2003; Li et al (2006Li et al ( , 2008. For the antitumor activity of aryl isoxazole amides (AIMs), see: Han et al (2009); Gajewski et al (2009).…”