Studies in the usnic acid series. II. The condensation of (+)-usnic acid with hydroxylamine

Abstract

The results of the reaction of usnic acid (1) with hydroxylamine are presented. Four products, two isomeric isoxazoles (2 and 4), a novel oxazocine structure (3), and Δ2,11-enaminousnic acid (5) were isolated and characterized. These data clarify the earlier published results in this area.

Studies in the usnic acid series. IV. The base catalyzed usnic acid – isousnic acid rearrangement. Part II. An improved synthesis of (+)-isousnic acid

“…Thus, the alkaline treatment of (+)-2H- [1,2]oxazocinousnic acid (3) (2) follows a very similar course to that previously observed (3) for the isomeric isoxazole 2 (2) producing 5 as the main component, (Fig. 1) the latter belonging to the isousnic acid series (the 'iso' series).…”

“…A solution of (+)-2H- [1,2]oxazocinousnic acid (3) (3.973 g, 11.651 mmol) in freshly prepared 20% aqueous potassium hydroxide (200 ml) was stirred at room temperature under a nitrogen atmosphere for 1.5 h. The dark brown reaction mixture was diluted with cold distilled water (200 ml), acidified with 1 N hydrochloric acid, and extracted with ethyl acetate (3 x 120 ml). The combined extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford a pale yellow foam (4.508 g).…”

“…Dehjldration of ( + )-a-Hj~droxydesacet,vl-2H-,1,2.~oxazo-cinoisorrsnic Acid ( 5 ) A solution of (+)-a-hydroxydesacetyl-2H- [1,2]oxazocinoisousnic acid (5) (970 mg, 3.059 mmol) in 0.5% concentrated sulfuric acid in acetic anhydride (10 ml) was heated at 55'C (oil bath temperature) under a nitrogen atmosphere for 1 h. The reaction mixture was poured onto crushed ice (20 g), extracted with ethyl acetate (3 x 10 ml), and the combined extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to produce a colorless foam (1.174 g), which upon purification by preparative chromatography afforded the following components. A solution of (+)-IV-acetyl-[l ,2]oxazocinoisousnic acid acetate (7) (325 mg, 0.848 mmol) in absolute ethyl alcohol (50 ml) was hydrogenated over platinum oxide (50 mg) at room temperature and atmospheric pressure.…”

“…One of these (67, yield) revealed a molecular formula, C,,H,,O,PJ and was clearly the result of C-acylation of the aromatic ring (8, Fig. 2 (2). Table 1 shows a comparison of the relevant 'Hmr characteristics of these two materials.…”

“…During our continued studies on nitrogen containing usnic acid derivatives (1,2) as useful synthetic intermediates for the preparation of the several biodegradation products isolated in our lab~ratories,~ we have recognized an interesting base-catalyzed usnic acid -isousnic acid rearrangement (3).…”