Transformation of 15-ene steviol by Aspergillus niger, Cunninghamella bainieri, and Mortierella isabellina.

Transformation of 15-ene steviol (ent-13-hydroxy-kaur-15-en-19-oic acid) by growth cultures of Aspergillus niger BCRC 32720, Cunninghamella bainieri ATCC 9244, and Mortierella isabellina ATCC 38063 was conducted to generate various derivatives for the development of bioactive compounds. Four previously undescribed compounds along with six known compounds were obtained. The newly identified isolates were characterized using 1D and 2D NMR, IR, and HRESIMS, and three compounds were further confirmed by X-ray crystallographic analyses.

Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives.

A series of novel isosteviol derivatives having C4-amide substituents were synthesized in order to test for antiviral effects against the hepatitis B virus (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of its antiviral activity was further analyzed using HBV-transfected Huh7 cells.

Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus.

Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N-methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in HepG2 2.2.15 cells.

Oxygenated compounds from the bioconversion of isostevic acid and their inhibition of TNF-α and COX-2 expressions in LPS-stimulated RAW 264.7 cells.

Fourteen oxygenated compounds were isolated from the preparative-scale biotransformation of isostevic acid (ent-beyeran-19-oic acid). Incubation of it with Aspergillus niger BCRC 32720 produced eight metabolites, four with Bacillus megaterium ATCC 14581, and another four with Mortierella isabellina ATCC 38063. In addition to their structural elucidation by NMR spectroscopy and HRMS, structures of four of these were further confirmed by X-ray diffraction studies.

Transformation of isosteviol lactam by fungi and the suppressive effects of its transformed products on LPS-induced iNOS expression in macrophages.

From the screening of 21 microbial strains, Absidia pseudocylindrospora ATCC 24169 and Aspergillus niger BCRC 32720 were found to reproducibly transform isosteviol lactam (4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam) (3) into various compounds. Preparative-scale transformation of 3 with Abs. pseudocylindrospora yielded two new hydroxylated compounds (4 and 5), with conservation of the lactam ring.

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

Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4alpha-carboxy-13alpha-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1beta,7alpha-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7alpha-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1beta,7alpha-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1beta-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8beta-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8beta-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses.

Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor.

A number of hydroxylated diterpenoids were obtained from the microbial transformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) (2) with Mucorrecurvatus MR 36, Aspergillusniger BCRC 31130, and Absidiapseudocylindrospora ATCC 24169. Incubation of 2 with M. recurvatus and Asp.

Microbial transformation of isosteviol lactone and evaluation of the transformation products on androgen response element.

Two filamentous fungi, Cunninghamella bainieri ATCC 9244 and Aspergillus niger BCRC 32720, were used to investigate the biotransformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16- seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) ( 2), which was derived by reacting isosteviol ( ent-16-oxobeyeran-19-oic acid) ( 1) with m-chloroperbenzoic acid. Incubation of 2 with C. bainieri afforded metabolites 3- 6, which involved isomerization, hydroxylation, and ring cleavage reactions followed by oxidation and selective O-methylation.