title: Effect of chain length and ring size of alkyl and cycloalkyl side-chain substituents upon the biological activity of brassinosteroids. Preparation of novel analogues with activity exceeding that of brassinolide.
abstract: A series of brassinosteroids with different alkyl or cycloalkyl substituents in place of the isopropyl group at C-24 of brassinolide (1) were prepared by the CuCN-catalyzed addition of Grignard reagents to (threo-2R,3S,5alpha,22R,23R,24S)-23,24-epoxy-6, 6-(ethylenedioxy)-2,3-(isopropylidenedioxy)-26, 27-dinorcholestan-22-ol (9), followed by deketalization and Baeyer-Villiger oxidation. Compound 9 was employed as part of a 70:30 threo/erythro mixture of epoxides 9 and 10, from which the erythro-epoxide 10 was recovered intact after the Grignard additions. Thus, the corresponding n-dodecyl, n-hexyl, n-propyl, tert-butyl, cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl analogues of brassinolide were obtained. A rearrangement byproduct was observed during the preparation of the cyclopropyl-substituted brassinosteroid when ether was used as the solvent in the Grignard reaction, but could be avoided by the use of THF. A method for recycling the undesired erythro-epoxide 10 was developed on the basis of deoxygenation with tellurium and lithium triethylborohydride. The rice leaf lamina inclination assay was then used to measure the bioactivity of the products. In general, increasing activity was observed as the length or ring size of the C-24 hydrocarbon substituent decreased. The novel cyclobutyl- and cyclopropyl-substituted analogues of brassinolide (1) were ca. 5-7 times as active as 1 and thus appear to be the most potent brassinosteroids reported to date. Further enhancement of the bioactivity of all of the above brassinosteroids, except that of the inactive n-dodecyl derivative, was observed when the brassinosteroid was applied together with an auxin, indole-3-acetic acid (IAA). The synergy between the brassinosteroids and IAA thus increased the bioactivity of the brassinosteroids, including the cyclopropyl and cyclobutyl derivatives, by ca. 1-2 orders of magnitude.
authors.affiliation: Departments of Chemistry and Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4. tgback@ucalgary.ca
authors.forename: T G
authors.initials: TG
authors.lastname: Back
authors.forename: L
authors.initials: L
authors.lastname: Janzen
authors.forename: S K
authors.initials: SK
authors.lastname: Nakajima
authors.forename: R P
authors.initials: RP
authors.lastname: Pharis
mesh_terms: D000478:Alkylation; D001937:Brassica / Q000737:chemistry*; D060406:Brassinosteroids; D002777:Cholestanols / Q000494:pharmacology*; D007202:Indicators and Reagents; D007210:Indoleacetic Acids / Q000494:pharmacology; D012275:Oryza / Q000187:drug effects; D010937:Plant Growth Regulators / Q000138:chemical synthesis* / Q000494:pharmacology; D018515:Plant Leaves / Q000187:drug effects; D013260:Steroids, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D060406:Brassinosteroids; D002777:Cholestanols; D007202:Indicators and Reagents; D007210:Indoleacetic Acids; D010937:Plant Growth Regulators; D013260:Steroids, Heterocyclic; C030737:indoleacetic acid; C023623:brassinolide