合成路线1

Diketopiperazine (I) is protected with benzylating reagents to give N,N'-dibenzyldiketopiperazine (II), which is brominated with Br2 to the dibromo derivative (III). The treatment of (III) with benzyl alcohol affords the dibenzyl ether (IV), which is condensed with the silylated methyl 4-hydroxycrotonate (V) by means of butyllithium, yielding the coupled product (VI). The reduction of the ester group of (VI) first with LiAlH4 and then with NaBH4 yields the primary alcohol (VII), which is protected with dimethyl tert-butylsilyl chloride giving the fully protected compound (VIII). Partial deprotection of (VIII) with H2 over Pd/C in ethanol pyridine eliminates the less shielded benzyl group, affording the secondary alcohol (IX), which is acetylated with acetic anhydride to the acetate (X). Selective deprotection of (X) with acetic acid-water THR at 80 C eliminates the dimethyl tert-butylsilyl group, yielding the alcohol (XI), which is cyclized by heating at 80 C in the presence of pyridinium p-toluenesulfonate, affording the bicyclo compound (XII). The aldol condensation of (XII) with the aldehyde (XIII) by mean of butyllithium yields the alcohol (XIV), which is desilylated with tetrabutylammonium fluoride to the primary alcohol (XV).