Lophenol

Tanaka and his group evaluated antihyperglycemic effects of five phytosterols named as lophenol (68), 24-methyllophenol (69), 24-ethyl-lophenol (70), cycloartanol (71) and 24-methylene-cycloartanol (72), isolated from Aloe barbadensis Miller, in type 2 diabetic db/db mice. In... 

Lophenol, trans-23-dehydro, 24-methyl Fixed q OE084... 

Azido-2,6-dinitro-4>acetami[Pg.21]

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

The presence of only 4 deuteriums in poriferasterol (4-B) formed from [C HjJmethionine in Ochromonas implies the formation of an intermediate ethyl-idene compound. Feeding experiments showed that the 28-Z isomers ethylidene lophenol (5-C) and isofucosterol (4-C) are both effectively incorporated into... 

Fig. 8. Formation of 24-methylene lophenol and 24-ethylidene lophenol from 24-methylene cycloartanol [9].

The next question is when in the biosynthetic pathway do the two methylations take place. As already indicated, experiments with enzyme preparations demonstrate that cycloartenol is the best substrate for the first methylation. However 24-methylene lophenol (5-F) and not 24-methylene cycloartanol (2-F), is the preferred substrate for the second methylation. This is formed by the pathway indicated in Fig. 8. 24-Methylene cycloartanol (2-F) is demethylated to cycloeucalenol (8-F) which is the substrate for cycloeucalenol obtusifoliol isomerase which opens the 9,19-cyclopropane ring to form obtusifoliol (13-F) demethylation at C-14 and isomerization... 

A - A ) (details of these reactions are still obscure) yields 24-methylene lophenol which is then methylated to 24-ethylidene lophenol. 

The second methylation step has recently been demonstrated in vitro in preparations from bramble cell cultures (Fonteneau et al., 1977). The enzyme, which is microsomal, is specific for 24-methylene lophenol (5-F) and will not act on substrates with an intact cyclopropane ring such as 24-methylene cycloartanol (2-F) the product of the reaction is 24-ethylidene lophenol (2-C). A similar enzyme which uses lanosterol (1-A) as substrate was reported in the uredospores of Uromyces phaseoli (Liu and Knoche, 1974), which is one of the few fungi which synthesize C29 sterols (Liu and Knoche, 1976). 

When methylene lophenol and ethylidene lophenol are converted to sterols, the following major changes have to occur in the molecule in addition to those already indicated in Section III (1) removal of the remaining 4a-methyl group, (2) conversion of a A derivative into a A derivative, and (3) insertion of a double bond into the side chain at C-22. 

VI. TRANSFORMATIONS INVOLVING 24-METHYLENE LOPHENOL AND 24-ETHYLIDENE LOPHENOL... 

Lophenol 4a-methyl-Sa-cholest-7-en-3p-ol, a zoo-and/or phytosterol (see Sterols), M, 400.69, m.p. 151 °C, [a]i, + 5° (CHCI3). L. has been isolated from rat tissues and feces, and from the cactus Lophocer-eus schotdL It has the structure of a tetracyclic triter-pene with a 3132-6frdemethyl-lanostane skeleton. Its structure is therefore intermediate between lanoster-ol and the sterols derived from lanosterol. 

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