Catalytic Synthesis of Secospirostanes A and B from (25R)-Spirost-5-en-3β-ol, a natural sapogenin

Diosgenin is a steroidal sapogenin abundant in Dioscorea spp. and a natural substrate of great importance for the semisynthetic production of bioactive compounds. Modification of the spirostane skeleton through oxidative ring opening (A or B) yields secosteroids, conformationally flexible analogs of brassinosteroids and ecdysteroids, with potential as synthetic phytohormones, therapeutic agents, and ecdysis modulators for insect control. We present the synthesis and characterization of a family of secospirostanes (types A and B) derived from diosgenin, using two complementary methodological approaches: (i) phase-transfer catalysis (PTC) with KMnO₄/TEBA/CH₂Cl₂ to obtain A-secoacids and cis diols, and (ii) oxidative ring-opening mediated by natural bentonite and m-chloroperbenzoic acid for the synthesis of B-secospirostanes with an unusual C3=C4-C5=O conjugated system. All compounds were characterized by FTIR, ¹H NMR, and ¹³C NMR, and preliminarily evaluated in vitro as plant growth promoters in radish (Raphanus sativus) hypocotyls and cotyledons. The preliminary results reveal that (25R)-5,6-seco-3-en-5-oxo-spirostan-6-oic acid (B-seco) acts as a selective auxin inhibitor, while methyl (25R)-2,3-seco-6-oxo-5α-spirostan-2,3-dioate (A-seco diester) exhibits dual-promoting activity (cytokinin and auxin) at nanomolar concentrations.

In terms of eco-sustainable green chemistry, the A-seco synthesis successfully replaces highly toxic, costly OsO₄ and N-methylmorpholine N-oxide with a low ecological impact PTC system utilizing aqueous solutions. Concurrently, the B-seco pathway substitutes aggressive reagents with a naturally occurring, reusable mineral clay under mild thermal conditions (50°C), offering clean, alternative processes for producing bioactive agrochemicals.