Synthesis and Biological Activity of New Brassinosteroid Analogs of Type 24-Nor-5ß-Cholane and 23-Benzoate Function in the Side Chain.

Brassinosteroids are polyhydroxysteroids that are involved in different plants' biological functions, such as growth, development and resistance to biotic and external stresses. Because of its low abundance in plants, much effort has been dedicated to the synthesis and characterization of brassinosteroids analogs. Herein, we report the synthesis of brassinosteroid 24-nor-5ß-cholane type analogs with 23-benzoate function and 22,23-benzoate groups. The synthesis was accomplished with high reaction yields in a four-step synthesis route and using hyodeoxycholic acid as starting material. All synthesized analogs were tested using the rice lamina inclination test to assess their growth-promoting activity and compare it with those obtained for brassinolide, which was used as a positive control. The results indicate that the diasteroisomeric mixture of monobenzoylated derivatives exhibit the highest activity at the lowest tested concentrations (1 × 10-8 and 1 × 10-7 M), being even more active than brassinolide. Therefore, a simple synthetic procedure with high reaction yields that use a very accessible starting material provides brassinosteroid synthetic analogs with promising effects on plant growth. This exploratory study suggests that brassinosteroid analogs with similar chemical structures could be a good alternative to natural brassinosteroids.

Synthesis of New Steroidal Carbamates with Plant-Growth-Promoting Activity: Theoretical and Experimental Evidence.

A priority of modern agriculture is to use novel and environmentally friendly plant-growth promoter compounds to increase crop yields and avoid the indiscriminate use of synthetic fertilizers. Brassinosteroids are directly involved in the growth and development of plants and are considered attractive candidates to solve this problem. Obtaining these metabolites from their natural sources is expensive and cumbersome since they occur in extremely low concentrations in plants. For this reason, much effort has been dedicated in the last decades to synthesize brassinosteroids analogs. In this manuscript, we present the synthesis and characterization of seven steroidal carbamates starting from stigmasterol, ß-sitosterol, diosgenin and several oxygenated derivatives of it. The synthesis route for functionalization of diosgenin included epoxidation and epoxy opening reactions, reduction of carbonyl groups, selective oxidation of hydroxyl groups, among others. All the obtained compounds were characterized by 1H and 13C NMR, HRMS, and their melting points are also reported. Rice lamina inclination test performed at different concentrations established that all reported steroidal carbamates show plant-growth-promoting activity. A molecular docking study evaluated the affinity of the synthesized compounds towards the BRI1-BAK1 receptor from Arabidopsis thaliana and three of the docked compounds displayed a binding energy lower than brassinolide.

Synthesis and biological activity of ring-A difluorinated brassinosteroids.

In this paper we report the synthesis of four ring-A difluorinated analogs of brassinosteroids. The bioactivity of these new compounds was evaluated using the rice lamina inclination test. The results show that one of these analogs elicits a bioactivity comparable to that of 28-homocastasterone, a highly active natural brassinosteroid. This finding suggests that both hydroxyls at C-2 and C-3 in active brassinosteroids are involved as hydrogen bond acceptors in their interactions with the cellular receptor.

Interaction of brassinolide with essential amino acid residues: a theoretical approach.

The interaction of the most active natural brassinosteroid, brassinolide, with the twenty natural amino acids is studied applying the multiple minima hypersurface method to model the molecular interactions explicitly. The resulting thermodynamic data gives useful information about the amino acids with the greatest association for brassinolide and the stabilities of such complexes. Density functional theory (DFT) optimizations were further carried out to test the performance of semiempirical calculations. Additional calculations with a more accurate DFT method were performed to explore the formation of this type of molecular complexes. The semiempirical geometries and stability order of these complexes are in good agreement with the DFT calculations. Each group of amino acids possesses a preferential zone of interaction with brassinolide, forming the polar-charged amino acids the most stable complexes. This study could contribute to future investigations of the interaction of brassinosteroids with the receptor protein in plants.

Synthesis and biological activity of brassinosteroids fluorinated at C-2.

In this paper we report the synthesis of four fluorinated analogues of brassinosteroids in which fluorine was introduced stereoselectively at C-2. The bioactivity of these new compounds was evaluated using the rice lamina inclination test. The results show that two of these analogues elicit high bioactivity, suggesting the involvement of hydrogen bond interactions between the active brassinosteroids and their cellular receptor.

A theoretical approach to the solvation of brassinosteroids.

The interaction of three different brassinosteroids with water was studied by the Multiple Minima Hypersurface (MMH) procedure to model molecular interactions explicitly. The resulting thermodynamic data give useful information on properties of molecular association with water. This application can serve as a tool for future investigations and modelling concerning interactions of brassinosteroids with receptor proteins in plants. DFT/B3LYP calculations were also made in order to correlate and test the performance of the current AM1 Hamiltonian calculations of these complexes, which are inherent to MMH routine. Diol functionalities located in ring A and lateral chain appears as the sites that show the highest affinity to water. The oxalactone group does not appear to be a key structural requirement in the association with water. Parallel calculations with a "polarizable continuum method" (PCM) agreed with the reported experimental order of biological activities, where Brassinolide exhibited the best solubility features.

Synthesis and biological activity of furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety.

Two furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety were synthesized and their biological activity studied using the bean second internode elongation test. One of the compounds produced significant stimulation at doses of 2.5 and 5ng/plant.