Biocatalysis: fungi mediated novel and selective 12β- or 17β-hydroxylation on the basic limonoid skeleton

Abstract

Basic limonoids carrying a 4,4,8-trimethyl-17-furanylsteroid skeleton are a class of triterpenoids and wellknown for their insecticidal as well as a vast array of pharmacological activities. Rare and synthetically challenging 12β-and 17β-hydroxylation was achieved on the basic limonoid skeleton to produce a novel series of hydroxylated limonoids using fungi-mediated biocatalysis. The fungal system belonging to the genera of Mucor efficiently converted azadiradione, epoxyazadiradione, gedunin and their derivatives into corresponding 12β-and/or 17β-hydroxy derivatives. The position and stereochemistry of hydroxylation was determined by rigorous spectroscopic and crystallographic studies. This fungi-mediated stereoand regio-selective hydroxylation process was highly efficient and mild enough to sustain chemically sensitive functional groups around the basic limonoid skeleton. Modifications of specific functional groups and variation in biocatalyst were shown to bring selectivity among 12β-or 17β-hydroxylation.

Fungal mediated kinetic resolution of racemic acetates to ( R )-alcohols using Fusarium proliferatum

“…Fermentation procedures were carried out as reported earlier. 31,34 Among various fungal systems screened for hydrolytic kinetic resolution of (1), Fusarium proliferatum was able to convert it to (R)-(À)-lavandulol (1a) in an efficient manner with very high ee. Biocatalytic resolution was validated with two independent control experiments; substrate control (with substrate and without organism), and organism control (with organism and without substrate).…”

“…On the other hand, whole cell biocatalysis offers an inexpensive choice in which enzymes are stable within cellular environment and the microbial cells themselves act as the source of cofactors for the biocatalyst mediated conversion. [31][32][33] The present study describes one-pot two-step de-esterification followed by selective (S)-enantiomer oxidation of seven acyclic and aromatic acetates using Fusarium proliferatum (National Collection of Industrial Microorganisms/NCIM, catalog no. 1105).…”

Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents

“…Limonoids possess 4,4,8-trimethyl-17-furanylsteroidal skeleton which is further substituted with other functional groups ( Fig 1 ). Neem limonoids can be classified skeletally into two groups; basic limonoids (4,4,8-trimethyl-17-furanylsteroidal skeleton such as azadirone, azadiradione, gedunin) and C-seco limonoids (with modified and rearranged C-ring such as azadirachtin, salannin, nimbin) [ 22 , 24 ].Very few studies on the tertranortriterpenoids effect on α-amylase are available. Recently, the tetranortriterpenoid meliacinolin and azadirachtolide isolated from A .…”

“…indica leaves, and swietenine from Swietenia macrophylla have been reported to exhibit α-amylase inhibitory activity in streptozotocin induced diabetes in mice [ 25 – 27 ]. On this basis, the current study involves nine neem limonoids four of C-seco type [azadirachtin A, azadirachtin B, salannin and nimbin] and five containing basic limonoid skeleton [azadirone, azadiradione, epoxyazadiradione, gedunin and 17β-hydroxyazadiradione] isolated and characterized in our previous study [ 24 , 28 , 29 ]. The goals of this study were (1) screening and identification of Neem limonoids as potent inhibitors of HPA on the basis of their inhibition potency and in vitro cytotoxicity on AR42J cell line (2) to reveal their mode of action and underlying molecular interactions with respect to molecular docking, inhibition kinetics and ligand binding.…”

Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients

“…In Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8 and Figure 9, we can see a variation in biocatalytic system introduce regio-selectivity among 12β- or 17β-hydroxylation in limonoids skeletons [23]. Cunninghamella elegans AS 3.1207 also transforms steroidal saponins into pregnenolones, S. racemosum AS 3.264 converts paeoniflorin into albiflorin [26].…”