Fucosterol epoxide

Other products were 7(3-hydroxydigitoxin and 7(3-hydroxydigoxin. Microbial transformation of [16oc-3H]-precursors gave [16a-3H]androstenedione and [16a-3H]-oestradiol.244 It was reported that Tenebrio molitor was able to convert the 247 ,285-isofucosterol epoxide into cholesterol more readily than the 245,287 -isomer, whereas no significant difference was observed for the reactivities of the 24,28-fucosterol epoxides.245 Incubation of phytosterol mixtures with a mutant strain of Mycobacterium fortuitum resulted246 in the accumulation of novel 24-oxo-steroids... 

Another series of inhibitors of sterol metaboUsm in insects were synthesized by our group. These are 24,28-iminofucosterol (104) [176], stigmasta-5,24(28),28-trien-3)8-ol (105) [177], and cholesta-5,23,24-trien-3(j8-ol (106) [177] (Fig. 19). When the imine (104) or the allene (105) was administered in the silkworm diet in combination with sitosterol or cholesterol, the growth and development of B. mori were markedly retarded. The imine was expected to inhibit the conversion of fucosterol epoxide to desmosterol, and this was verified by in vitro experiments where the imine, at the same level as the substrate [ H]fucosterol epoxide (92), completely blocked the transformation into desmosterol. However, the imine may not exert its effect solely by limitation of desmosterol or cholesterol formation because cholesterol as the sole dietary sterol was unable to prevent the inhibitory effect. In contrast, the allene (106) seemed to exert little effect on sitosterol dealkylation because the sterols in silkworms fed on the allene (106) in combination with sitosterol were essentially the same as in controls. 

The sterols that were chosen as substrates contained two double bonds, one at various positions in the side chain and A5 in the steroid nucleus. Whereas the latter double bond was never touched in reactions with the Fe(III) porphyrin vesicle system 183 in the presence of PhIO, the side chain double bonds of desmosterol 186 and fucosterol 187 were epoxidized to 188 and 189 in 32% and 22% yield, respectively (Fig. 31). In contrast, stigmasterol 190 was not reactive, since the double bond cannot approach the reactive iron-oxo intermediate. 

The 24,28-epoxide (581) derived from fucosterol (or its acetate) reacts with BF3 to give the 28-oxo-compound (582), by a simple hydride migration and the 24-dehydro-compound (583 desmosterol), resulting from fragmentation of the 24,28-bond. The fragmentation has several precedents. ... 

Figure 2. Pathways of conversion of C-24 alkyl sterols to cholesterol in the tobacco hornworm and other phytophagous insects. Fucosterol 24,28-epoxide has been shown to be an intermediate between fucosterol and desmosterol in Bombyx mori and Tenebrio molitor.

Coleoptera. The confused flour beetle, Tribollum confusum, was the first phytophagous insect we found that produces an appreciable amount of a sterol other than cholesterol from radiolabeled dietary C28 and C29 phytosterols. We found this insect produced large quantities of 7-dehydrocholesterol, equivalent to as much as 70% of the total tissue sterols isolated (12). It was further determined that cholesterol and 7-dehydrocTfolesterol were in equilibrium in this flour beetle. Another new intermediate, 5,7,24-cholestatrien-3B-ol was identified as an intermediate between desmosterol and 7-dehydrocholesterol (Figure 3). We found very similar pathways of sterol metabolism to exist in the closely related flour beetle, Tribolium castaneum (13). However, another flour beetle, Tenebrio moHtor, nad only about one-third or less of the levels of 7-dehydrocholesterol as the two Tribolium species, but still much higher levels of this sterol than has been found in most species. Fucosterol 24,28-epoxide was also implicated as an intermediate in the synthesis of cholesterol from sitosterol in T. mol i tor (14). 

Configurations assigned in 1975 to the 24,28-epoxides (31) of fucosterol and the derived 24,28-diols (32) and (33), by c.d. study of their Pr(dpm)3 complexes, have now been revised on the basis of chemical transformations which included conversion into the known 24-ethyl isomers clionasterol and sitosterol.The earlier error is attributed to mistaken judgement of the most stable conformations of the glycol-Pr(dpm)3 complexes. 

H]Fucosterol-24,28-epoxide (484) was found to be effectively incorporated into cholesterol in the silkworm. This unusual in vivo transformation... 

Fucosterol 24,28-epoxide 24-Methylenecholesterol 24,28-epoxide Stigmasterol-24,28-epoxide... 

As mentioned earlier, much of the information on dealkylation and conversion of C28 and C29 phytosterols to cholesterol in insects (Figure 2) has been acquired through research with two lepidopteran species, the tobacco homworm, Af. sexta (3, and references therein) and the silkworm, B. mori (5, and references therein). Studies with Af. sexta established that desmosterol is the terminal intermediate in the conversion of all phytosterols to cholesterol, and that fucosterol and 24-methylenecholesterol were the first intermediates in the metabolism of sitosterol and campesterol, respectively, to cholesterol (5). In-depth metabolic studies with B. mori first demonstrated the involvement of an epoxidation of the A - -bond of fucosterol or 24-methylenecholesterol in the dealkylation of sitosterol and campesterol (5,45). More recently, the metabolism of stigmasterol was elucidated in detail in another lepidopteran, Spodoptera littoralis, and the side chain was shown to be dealkylated via a A " -bond and a 24,28-epoxide as were sitosterol and campesterol (46). The only significant differences in the metabolism of stigmasterol are the involvement of the additional 5,22,24-triene intermediate preceding desmosterol in the pathway and reduction of the A -bond prior to reduction of the A -bond (Figure 2). 

Since insects do not synthesize sterols, they are dependent upon a dietary supply of these essential compounds. Phytophagous insects transform the dietary C g- and Cj -sterols into C2. -sterols (usually cholesterol) before they are used for various l unctions, including structural components of membranes and moulting-hormone precursors. This dealkylation process has been re-viewed, and it appears that fucosterol (135) is an intermediate in the conversion of sitosterol (134) into cholesterol. Scheme 10 has been proposed as a main dealkylation pathway in Bombyx mori, based on the efficient incorporation of [ H]fucosterol 24,28-epoxide (136) into cholesterol (138) and also trapping of (136) as a probable intermediate in the conversion of fucosterol... 

---