Cyclization of (5R)-5-hydroxy-L-lysine (VIII) by means of EDC and HOBt afforded the caprolactam (IX). The amino group of (IX) was then protected as the N-Boc derivative (X) by treatment with Boc2O. Hydroxyl group acylation in (X) with cyclohexanecarbonyl chloride (XI) produced ester (XII). The Boc protecting group of (XII) was then removed by treatment with trifluoroacetic acid, yielding the aminocaprolactam (XIII). Coupling of amine (XIII) with lactone (VII) in refluxing isopropanol produced amide (XIV). The title compound was then obtained by acidic hydrolysis of the remaining acetonide function of (XIV).
The cyclization of 4-methyl-4-(N-methylaminoethyl)-6-methoxy-3,4-dihydronaphthalene-1(2H)-one (I) with formaldehyde in hot methanol gives 1,4-dimethyl-10-methoxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine-7(6H)-one (II), which is reduced with LiAlH4 in refluxing methanol yielding 1,4-dimethyl-10-methoxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine-7-ol (III). Finally, this compound is reduced further with HI and P in refluxing acetic acid - water.
alpha-D-Glucoheptonic acid gamma-lactone (I) was protected as the bis(acetonide) (II) upon treatment with a catalytic amount of I2 in acetone. The free hydroxyl group of (II) was then alkylated with iodomethane in the presence of silver oxide, yielding the methyl ether (III). Selective hydrolysis of the 1,2-acetonide of (III) was accomplished by treatment of the bis(acetonide) (III) with aqueous acetic acid. Oxidative cleavage of the resultant vicinal diol (IV) using NaIO4 gave aldehyde (V). Then, olefination of aldehyde (V) with the low-valent organochromium species generated in situ from 1,1-diiodoneopentane (VI) and CrCl2 produced the target E-olefin (VII) as the major isomer.