Synthesis and C-25 Chirality of 26-Hydroxycholesterols

Samples of cholest-5-ene-3β,26-diol 3-tetrahydropyranyl ether were prepared via hydroboration of cholest-5,25-dien-3β-ol tetrahydropyranyl ether with (a) disiamylborane, (b) (+)-diisopinocampheylboranes (DIPCB), and (c) (-)-(DIPCB). The 26-hydroxy compounds were converted first to cholest-4-en-3-on-26-ol p-bromobenzoates and then to cholest-4-ene-3β,26-diol 26-p-bromobenzoates. Authentic (25R)- and (25S)-cholest-4-ene-3β,26-diol p-bromobenzoates were prepared from kryptogenin and from (25S)-cholest-4-en-3-on-26-ol p-bromobenzoate, respectively. The magnitudes of the Cotton effects of the 25R and 25S samples were the same but of the opposite sign. The 25R compound had a negative Cotton effect while the 25S compound had a positive Cotton effect. Both compounds were assumed to be optically pure (100%). The CD spectra of the corresponding analogs derived from the hydroboration of the C-25 olefin were recorded. Based on the sign and amplitude of their Cotton effects, their stereochemistry and optical purity at C-25 was defined.