Optically active cis- and trans-3-(1-hydroxyethyl)-1,5-benzothiazepin-4-ones 4 and 5 have been synthesised by ring transformation of (E)- and (Z)-5-ylidene-1,3-dioxan-4-ones 1 with 2-aminothiophenol. Stereoselective conjugate addition of the –SH group of 2-aminothiophenol to the Michael system of the chiral 5-ylidene-1,3-dioxan-4-one 1, catalysed by BuLi, gave adducts 2 and 3. The stereochemical mode of attack can be rationalised by hydrogen bonding of the attacking 2-aminothiophenolate with the oxygen atoms of the dioxanone ring. Treatment of the adducts 2 and 3 with ethylmagnesium bromide afforded ring transformation by attack of the amino group at the carbonyl carbon atom cleaving the dioxanone ring. The resulting 3-(1-hydroxyethyl)-1,5-benzothiazepin-4-ones 4 and 5 represent structural analogues of Diltiazem®, a widely used drug in the treatment of hypertension.
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