Enzymic transformation of an acyclic sesterterpene terminal epoxide into a lanosterol analogue

SUBSEQUENT to the finding that squalene 2,3-oxide is a general intermediate in the enzymic conversion of squalene into lanosterol and other 3-hydroxylated sterols, the transformation of structurally modified squalene oxides into sterol-like products was first reported from these laboratories.' In that preliminary study, the effect on side-chain reduction and shortening was tested and found not to deter seriously the biological cyclization process. In extending this approach, we have now determined that the absence of an entire isoprenoid unit from the non-oxidized terminus of squalene oxide does not prevent normal biochemical cyclization : constant. Another portion of the crude sterol product was silylated with trimethylsilyl chloride in pyridine and subjected to fractionation by preparative g.1.c. (5% diethyleneglycol succinate a t 190"), 47% of the radioactivity appearing in a single peak having the same retention time (Rcholestane 0.71) as the trimethylsilyl ether of authentic (11). The radioactive silyl ether was collected, hydrolysed with ethanolic KOH, and subjected to preparative g.1.c. on an XE-60 column at 180"; 91% of the activity was found in a fraction with the same retention time (Rcholestane 1-90) as authentic (11).