Characterization and Biological Activities of Four Biotransformation Products of Diosgenin from Rhodococcus erythropolis.

Diosgenin (DSG), a steroidal sapogenin derived from the tuberous roots of yam, possesses multiple biological properties. DSG has been widely used as a starting material for the industrial production of steroid drugs. Despite its significant pharmacological activities, moderate potency and low solubility hinder the medicinal application of DSG. Biotransformation is an efficient method to produce valuable derivatives of natural products. In this work, we performed the biotransformation of DSG using five Rhodococcus strains. Compounds 1-4 were isolated and identified from Rhodococcus erythropolis. Compounds 1 and 2 showed potent cytotoxicity against the A549, MCF-7, and HepG2 cell lines. Compounds 3 and 4 are novel entities, and each possesses a terminal carboxyl group attached to the spiroacetal ring. Remarkably, 4 exhibited significant cell protective effects for kidney, liver, and vascular endothelial cells, suggesting the therapeutic potential of this compound in chronic renal diseases, atherosclerosis, and hypertension. We further optimized the fermentation conditions aiming to increase the titer of compound 4. Finally, the yield of compound 4 was improved by 2.9-fold and reached 32.4 mg/L in the optimized conditions. Our study lays the foundation for further developing compound 4 as a cell protective agent.

Pd(II)-Catalyzed Tandem Enantioselective Methylene C(sp3 )-H Alkenylation-Aza-Wacker Cyclization to Access ß-Stereogenic γ-Lactams.

Herein, we describe an unprecedented cascade reaction to ß-stereogenic γ-lactams involving Pd(II)-catalyzed enantioselective aliphatic methylene C(sp3 )-H alkenylation-aza-Wacker cyclization through syn-aminopalladation. Readily available 3,3'-substituted BINOLs are used as chiral ligands, providing the corresponding γ-lactams with broad scope and high enantioselectivities (up to 98 % ee).

Synthesis of Acyclic Aliphatic Amides with Contiguous Stereogenic Centers via Palladium-Catalyzed Enantio-, Chemo- and Diastereoselective Methylene C(sp3)-H arylation.

The enantioselective desymmetrizing C-H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp3)-H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,ß-contiguous stereogenic centers via PdII-catalyzed asymmetric arylation of unbiased methylene C(sp3)-H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of ß-Ar1-ß'-Ar2-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.