Chemical Semisynthesis and Biotransformation with Rhizopus nigricans of Several Sesquiterpenes: Obtention of New 1α- and 2α-Hydroxyselinane Derivatives

Chemical-Microbiological Synthesis of Cryptomeridiol Derivatives by Gliocladium roseum: Semisynthesis of 11-Hydroxyeudesmanolides

“…26 The main metabolite isolated (7) had a molecular formula of C 17 H 28 O 5 , which indicated the presence of an additional hydroxyl group in the molecule. The -effects on C-7, C-12, and C-13 detected in its 13 C NMR spectrum indicated that hydroxylation had occurred at C-11, establishing its structure as 6 -acetoxy-4 ,11-dihydroxyeudesman-1-one. This major metabolite (7) was also a 4-epicryptomeridiol 19 derivative, obtained from incubation of substrate 1 with R. nigricans.…”

“…Measurements of NMR spectra (300.13 MHz 1 H and 75.47 MHz 13 C) were made in CDCl3, CD3COCD3, or CD3OD (which also provided the lock signal) with Bruker spectrometers (AM-300, ARX-400, and AMX-500). The assignments of 13 C chemical shifts were made with the aid of distortionless enhancement by polarization transfer (DEPT) using a flip angle of 135°. One-dimensional NOE difference experiments were made by irradiation for 4 s in series of eight scans with alternation between on-and offresonance.…”

“…Biotransformation of 2. Substrate 2 (450 mg) was dissolved in EtOH (7 mL), distributed among seven Erlenmeyer flask cultures of G. roseum and incubated for 15 days, after which the cultures were processed as indicated above for the biotransformation of 1, to give a mixture, which was chromatographed on a silica gel column to obtain 58 mg (13%) of starting material 2, 22 mg (5%) of 6 -acetoxy-4R-hydroxyeudesm-11-en-1-one (9), 43 mg (9%) of 6 -acetoxy-1R,4R-dihydroxyeudesmane (10), 92 mg (19%) of 6 -acetoxy-4R,8R-dihydroxyeudesman-1-one (11), 150 mg (32%) of 6 -acetoxy-4R,11-dihydroxyeudesman-1-one (12), 18 mg (4%) of (11S)-12-acetoxy-4R,6 ,11-trihydroxyeudesman-1-one (13), and a mixture of metabolites, from which, after treatment with LiAlH 4, 1 ,4R,6 ,8R,11-pentahydroxyeudesmane (14, 19 mg, 4% of overall yield) was isolated. -4r-hydroxyeudesm-11-en-1-one (9 …”

“…3 Eudesmane sesquiterpenes are common in nature, 4,5 and in the past decade, several biotransformations of these kinds of compounds have been carried out to acquire products difficult to achieve by chemical means. [6][7][8][9][10][11][12][13][14][15][16] Cryptomeridiol is a natural sesquiterpene diol 17 that exerts a potent antispasmodic effect on the isolated rabbit ileum, 18 and 4-epi-cryptomeridiol is also a natural compound. 19 Sesquiterpene lactones show a wide variety of remarkable biological activities, but many of them present strong cytotoxic properties, apparently due to the R, -unsaturated lactone group.…”

Improved microbiological hydroxylation of sesquiterpenoids: semisynthesis, structural determination and biotransformation studies of cyclic sulfite eudesmane derivatives

“…Therefore, we have previously described several biotransformations of diverse eudesmane substrates by different filamentous fungi, and we have isolated metabolites in which we observed both regio-and stereoselective hydroxylation. [22][23][24][25][26] The main action of these microorganisms was directed to the isopropyl moiety, and some of these isolated metabolites have been used, by combination with chemical methods, to synthesise natural sesquiterpene derivatives such as 6α-and 6β-sesquiterpenolides. 23, 24 These biocatalytic studies have also shown the influence on the bioconversion yields of the configuration of a hydroxy group at C-4 in eudesmane compounds.…”