Synthesis of brassinosteroids

Chemical synthesis of brassinosteroids, phytohormones with a seven-membered O-heterocycle in some of them 02KPS99. 

Synthesis of Brassinosteroids. USDA scientists were the first to report the synthesis of various brassinolide analogs, some of which were later found to be present in plants. This work led to, in addition to identifying new brassinosteroids from plants, establishing the structure—activity relationship of brassinosteroids. The reasons for undertaking the synthesis were (a) to ascertain that brassinolide was indeed the active ingredient of the pollen, (b) to determine structure—activity relationships, and (c) to provide quantities of the active ingredient(s) sufficient for biological studies and field work. 

Abscisic acid (ABA) levels in rice plants, 308,31Or levels in squash hypocotyls, 315/.316 Active component of brassins identification, 9,lQf pilot plant extraction, 6,7/,8 solvent partition and column chromatography, 8 Adventitious root(s) development, 233,234r,235 formation, 247 Agriculture, application of 24-epibrassinolide, 280-290 22-Aldehydes, synthesis of brassinosteroids, 47-50f a hormone function, description for brassins, 4... 

In our synthesis of brassinosteroids, organoaluminum chemistry was proved to be useful in constructing the side-chain double bond with the desired geometry, and the stereoselective cleavage of epoxides was shown to be an excellent method to generate the correct configuration of the side-chain. 

From 1980 to 1988, we worked on the synthesis of brassinosteroids, another important group of phytohormones. Brassinolide was isolated in 1979 from Brassica napus in a small amoimt (4 mg from 40 kg of pollen) as a plant-growth promotor. We synthesized brassinolide [5], and also prepared non-natural 25-methylbrassinolide [6]. The latter was more bioactive than the former. These brassinosteroids were very easily metabolized by plants, and could not be used practically. Thus, natural products often remain only as prototypes of practically useful man-made products. 

Be this as it may, the CH oxidation has become an attractive and promising preparative method in natural-product synthesis. For example, dioxiranes have been used to introduce selectively a hydroxy group at the C-25 position of steroids, a challenging task not readily achieved with other oxidants. A specific case is the TFD oxidation of brassinosteroid (equation 33) . 

This ene reaction can be used to effect synthesis of the side chain present in the plant growth brassinosteroids (equation I). 

During the decade since publication in 1979 of the structure of brassinolide (I), and the synthesis of the first brassinosteroid (2), also in 1979, events related to the "brassins project have taken some interesting turns. At this point (October 1990), there seems to be little interest in developing brassinosteroids for agricultural... 

This brief review covers the period of the last ten years in the development of brassinosteroid chemistry in our laboratory. Our interest has been focused on the synthesis of natural brassinosteroids (brassinolide, homobrassinoli-de, epibrassinolide, norbrassinolide, etc.), their analogues and intermediates starting from stigmasterol, ergosterol, or pregnenolone. Some aspects of biological activity are discussed. 

Some structure-activity relationships, synthesis of new brassinosteroids, and new sensitive bioassays for brassinosteroids are presented. 

It has been assumed (21) that the fresh-weight gain of radish cotyledons by kinetin is due to the activation of de novo synthesis of the hydrolytic enzyme invertase. Seeking a similar influence of brassinosteroids on this enzyme we also found, that brassinolide 1 and (22S,23S)-homobrassinolide 3 treatment resulted in an increased activity of the soluble invertase even to a remarkably higher extent than kinetin in the case of brassinolide 1 (Figure 2). This increase... 

Effect of Brassinosteroids on Protein Synthesis and Plant-Cell Ultrastructure under Stress... 

Scheme 2 A working hypothesis of how brassinosteroids might interfere with the cell cycle of tobacco tumor cells (see ref. 17 for a discussion of the effects of compounds other than brassinosteroid). Putative control points, where synthesis of mevalonate appears to be mandatory, are indicated.

The first chemical synthesis of brassinolide was achieved by us in 1980 (5), but its multi-step synthesis process indicated costly preparation for agricultural use. The situation did not change, even after the discovery of many different synthetic routes were discovered. Thus, only a few brassinosteroids candidates have been tested in the field during the past several years. 

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