Transformation of isosteviol oxime to a lactone under Beckmann reaction conditions

Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages☆

“…On the other hand, the results also suggested that substrate 2 might be hydrolyzed to isosteviol (1) first, and then converted to the 6 and 7 by hydroxylation and Baeyer-Villiger reaction, respectively. Although substrate 2 can be transformed into lactone and lactam derivatives under concentrated hydrochloric acid in an ampoule at 180°C, 21 this is the first report to yield these two products by microbes. Asp.…”

“…Among these, [3][4][5]8, and 9 are new compounds, whereas 6, 7, and 10 have previously been reported. 13,20,21 The structures of these isolated compounds were elucidated through analysis of 1D and 2D NMR spectroscopic data, with 3-5 being further confirmed by X-ray crystallographic studies.…”

“…According to the literature, 21 the formation of lactone 7 might be from the introduction an OH group into nitrile carbocation and subsequently cyclization to yield imidate, which was hydrolyzed to 7. On the other hand, the results also suggested that substrate 2 might be hydrolyzed to isosteviol (1) first, and then converted to the 6 and 7 by hydroxylation and Baeyer-Villiger reaction, respectively.…”

Synthesis of Skeletally Diverse and Stereochemically Complex Library Templates Derived from Isosteviol and Steviol

“…The ketone function of 7 was converted to the corresponding oxime 8 in 93% yield on treatment with hydroxylamine and potassium acetate. Reaction with thionyl chloride as reported 17 then delivered nitrile 9 , the corresponding Beckmann fragmentation product, in 65% yield and lactam 10 in 27% yield. The Beckmann fragmentation is well precedented 18 in systems with a quaternary α-carbon.…”

“…Although the Beckmann rearrangement has previously been reported 17 regarding an analogous substrate (the N -methyloxime), the lactam was sufficiently attractive to warrant further investigation. Methylation of the carboxylic acid moiety of isosteviol ( 6 ) under standard conditions delivered methyl ester 7 .…”