Brassinolides structures

Inspection of the brassinolide structure revealed that the molecule is unique, because it contains 13 asymmetric centers, not found in any other steroid. With these many asymmetric centers, theoretically 213 (= 8192) stereoisomers can be derived when one undertakes the total synthesis of brassinolide, but nature produces only one isomer. Chemists in recent years, however, have designed synthetic schemes in such a way that the desired isomer can be obtained very selectively or specifically. Because... 

It is of interest that the structure of brassinolide resembles that of the insect molting hormone, ecdysone, which also is of plant origin. The structure of ecdysone is shown in Figure 1 and differs from the structure of brassinolide in that the orientation of the vicinal hydroxyl group at C-2 and C-3 is beta, the A/B junction is cis rather than trans as in the brassinolide structure and that ecdysone lacks the lactone oxygen in the B-ring. 

The trivial and lUPAC equivalent names of brassinosteroids and related compounds are given in Table 1. It should be noted, with the exception of typhasterol and teasterone, that the sterochemistry of the 2,3- and 22,23- diol groupings are alpha oriented, as in the brassinolide structure, and that they differ from the brassinolide structure only by the alkyl substituent at C-24 and the degree of oxidation of the B-ring (Figure 2). All of the brassinosteroids listed are biologically less active than brassinolide. 

Dolichosterone. Dolichosterone is the methane derivative of caststerone and differs from the brassinolide structure by the absence of the lactone function in the B-ring and by having a methylene rather than a methyl function at C-24. The brassinosteroid was isolated from immature seeds of Dolichos lablab (hyacinth-bean)... 

FIGURE 12-28 Structural similarities between plant and animal signals. The plant signals jasmonate, indole-3-acetate, and brassinolide resemble the mammalian signals prostaglandin E1 serotonin, and estradiol. 

Among the compounds that have been isolated from the brassins were a new group of glucosyl esters of fatty acids, the structures of which were established by spectral methods (254, 255) as well as by chemical and biochemical synthesis (256, 257, 258). Although these esters were much less active than brassinolide in the bean second internode bioassay, their presence may be essential for seed germination since the enzymatic synthesis of these esters was correlated to germination (257, 258). 

Structure-activity relationship Biosynthesis and Metabolism Biosynthesis of castasterone Biosynthesis of brassinolide from castasterone Regulation of biosynthesis Metabolism and its regulation Physiology and Signal Transduction Physiology Signal transduction Jasmonates and Oxylipins Introduction Chemistry Chemical structure Chemical stability... 

T. Yokota K. Mori, Molecular Structure and Biological Activity of Brassinolide and Related Brassinosteroids. In Molecular Structure and Biological Activity of Steroids M. Bohl, W. L. Duax, Eds. CRC Press Boca Raton, FL, 1992 pp 317-340. 

The use of Z-ray diffraction to assign structures to unusual steroid derivatives has been briefly reviewed.3 It includes reference to brassinolide (3), a steroidal plant growth hormone. Another unusual product assigned its structure by the X-ray method is the spiro-lactone (4), derived by thallium triacetate oxidation of 5a-cholestane-3,4-dione.4... 

The structure of the unique biologically active plant growth promoter, brassinolide, from pollen of the rape plant (Brassica napus L.) was published in 1979 (1). That... 

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... 

The isolation and structural determination of brassinolide [BR] was reported in Nature by Dr. N. B. Mandava and co-workers at the USDA in 1979(5), and was subsequently announced in Chem, Eng, News 6). The steroidal skeleton of the chemical structure of BR prompted us to examine the effect on the LJT. (225,235)-homobrassinolide was synthesized by Mori in 1980( 7) at our request just after the structural determination of BR. BR itself was also produced by Ikekawa and his co-workers the same year(3). Wada, a co-worker in our group, tested the activity of BR and homobrassinolide on rice lamina inclination and found that both compounds dramatically induced the inclination of laminae (see Table I) as expected(5). These findings strongly suggested... 

From 40 kg of rape pollen, 4 mg of an active compound was eventually isolated and shown to be the novel plant growth substance brassinolide (1) (3). The structure, as determined by X-ray crystallography, was [ (2a, 3a, 22R, 23R)-tetrahydroxy- 24 a-methyl-B-homo-7-oxa-5a-cholestane-6-one]. This structure was unique in possessing a 24a-methyl, a 7-oxalactonic B ring, and vicinal hydroxyls on the A ring (C2a and C3a) plus a side chain (C22R and C23R ). 

Figure 1. Structures of free hrassinosteroids from plants. 1 brassinolide, 2 dolicholide, 3 castasterone, 4 dolichosterone, 5 6-deoxodihydrocastasterone, 6 6-deoxodihydrodolichosterone, 7 typhasterol, 8 teasterone, 9 24-epicastasterone, 10 homodolicholide 11 homodolichosterone, 12 24-ethylbrassinone, 13 6-deoxodihydrohomodolichosterone, 14 28-norbrassinolide, 15 brassinone, 16 2-epiacstasterone, 17 3-epicastasterone, 18 2,3-diepicastasterone, 19 3,24-diepicasta-sterone, 20 3-epi-6-deoxodihydrocastasterone, 21 ip-hydroxycastasterone, 22 3-epi-l-a-hydroxycastasterone, 23 25-methyldolichosterone, 24 2-epi-25-methyldoli-chosterone, 25 2,3-diepi-25-methyldolichosterone, 26 2-deoxy-25-methyldolicho-sterone, 27 3-epi-2-deoxy-25-methyldolichosterone, 28 6-deoxodihydro-25-methyldolichosterone, 29 24-epibrassinolide.

Brassinosteroids are grouped into C, Cg, and steroids like the typical phytosterols. These classifications result basically from different alkyl substitutions in the side chain, that is no substituent in steroids (14, 15 ), a methyl (1, 3,5, 7-9, 16-22,29) or an exomethylene ( 2,4, 6) at C24 in steroids, and an ethyl at C24 (12 )or an ethylidene at C24 ( 10,11, 13) or an exomethylene at C24 with a methyl at C25 ( 23-28 ) in steroids. The structure-activity relationship reveals that alkylation in the side chain is necessary for biological activity. More especially, the presence of a saturated alkyl ( a methyl or an ethyl ) at C24 and a methyl at C25 makes brassinosteroids biologically more active. Thus, 25-methylbrassinolide bearing both 24-methyl and 25-methyl functions has been chemically synthesized and it is more potent than brassinolide which, until now, had been considered to be the most potent brassinosteroid (44). 

The identification of brassinolide (1) by workers at the USDA laboratories in Beltsville, Maryland in 1979 (1) was a most significant event because it established steroids as a new class of plant hormones. We were particularly interested in the structure of brassinolide as a result of our studies with somewhat... 

We have developed a synthesis of antheridiol in which the key step is an aldol condensation of a C-22 aldehyde with the anion derived from 3-isopropyl-but-2-enolide (4) which gives directly the sidechain of antheridiol as illustrated by structures 2 and 3. In this reaction, chiral centers are created at C-22 and C-23. The stereochemistry at C-22 in the major product is that predicted by the Cram rule (i.e. R) and careful study of the reaction showed that the stereochemistry at C-23 is determined by the temperature at which the aldol reaction is carried out. If the temperature is maintained below -70 °C, the major product has the R configuration at C-23. Thus, this method could be used to construct the sidechain of brassinolide with correct stereochemistry at C-22 and C-23. 

However, some side chain epimers like 24-epibrassinolide 2, trisepi-brassinolide and (22S,23S)-homobrassinolide 3 show remarkable activity and are therefore used widely for biological experiments. Furthermore several structural analogs with a shortened side chain moiety are active in specific test systems (7). Thus, structure-activity relationships of brassinosteroids are a field of continual development and require further examination. 

In 1970, Mitchell et al. (1) isolated from pollen of rape a lipoidal complex termed "brassins" that has growth-promoting effects on plants. The active compound was eventually identified as a steroid derivative, which was given the name brassinolide (2). In the same year, two highly physiologically active brassinosteroids (a generic term for all compounds structurally related to brassinolide), 225,235,245 (tri-epi)-brassinolide (further referred to as BR-1) and 22/ ,231 ,245 (epi)-brassinohde (BR-2) were synthesized (3, 4). Ever since various synthetic routes have been developed to synthesize BR and its isomers (see elsewhere in this volume). 

Scheme 1 Structures of steroids used in this study. The stereochemistry of natural brassinolide compared to the synthetic analogs (BR-1 and BR-2) is indicated.

---