The development and use of a general route to brassinolide, its biosynthetic precursors, metabolites and analogues

Abstract

A new method for the construction of steroid side chains through the addition of lithium salts of dithianes to a C-22 aldehyde was developed. An efficient one-pot procedure for the preparation of a suitable C-22 aldehyde from commercial epibrassinolide in three steps in 86% isolated yield was described. Enantioselective hydroxymethylation of isovaleraldehyde and Kulinkovich cyclopropanation of silylated Roche esters were used as key steps for the dithiane syntheses. The method was applied for the preparation of brassinolide, its biosynthetic precursors and metabolites. In addition, a number of brassinosteroids with a double bond in the side chain were prepared as precursors for tritiated derivatives for biosynthetic studies.

Synthesis of brassinosteroids with a keto group in the side chain

“…A potentially useful reaction for the differentiation between 2a,3a-and 22,23-diol groups in BS is the formation of cyclic boronic or boric esters [13,[15][16][17]. The reaction proceeds regioselectively at the side chain diol group in a high yield, but the removal of such protecting groups is not an easy task.…”

“…(22R,24R)-2a,3a,22-Trihydroxy-B-homo-7-oxa-24-methyl-5a-cholestan-6,23-dione(16) A mixture of acetonide 14 (80 mg), AcOH (8 mL) and water (2 mL) was stirred at 60°C for 1 h, then the solvents were evaporated in vacuo and the residue was purified by flash chromatography on silica gel (CHCl3 -EtOAc = 95:5 ? 85:15) to give compound 16 (72 mg, 97%) as white crystalls.…”

Brassinosteroid-BODIPY conjugates: Design, synthesis, and properties

“…The title compound (270 mg) was prepared as a colorless oil in 53% yield starting from (20S)-2α,3α-isopropylidenedioxy-20-formyl-B-homo-7-oxa-5α-pregnan-6-one (4b) (available from epibrassinolide (3b) according to [25]) as described above for the preparation of 6a. 1 13 at 65°C for 7 h under argon, then acetic acid (1.6 mL) and water (0.4 mL) were added and the resulting solution was left stirring at 70°C for 4h.…”

“…Carboxymethoxylamine hemihydrochloride (7.1 mg, 32.5 µmol) was added to the solution of castasterone 11 (10.0 mg, 21.5 µmol, prepared according to [25]) in pyridine (0.5 mL). The 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 11 resulting mixture was stirred at 60°C for 24 h and evaporated to dryness.…”

An improved synthesis of [26‐2H3]castasterone

“…The latter task can be greatly simplified by choosing steroids as a starting point that already are bearing the necessary functional groups. Such an approach has proved to be effective in terms of time and effort for the synthesis of many BS starting from epibrassinolide (an active ingredient in BS‐based preparations for agriculture) and epicastasterone (synthetic intermediate of epibrassinolide).…”