Synthesis of 24ξ-squalamine, an anti-infective steroidal polyamine

Article abstract of DOI:10.1021/jo00121a033

Squalamine (1) is a novel steroidal polyamine which exhibits broad spectrum anti-infective activity. It inhibits the growth of bacteria, both Gram positive and Gram negative, and fungi. The synthesis of 24ξ-squalamine was accomplished in 17 steps from 3β-hydroxy-5-cholenic acid. The stereospecific introduction of the 7α-hydroxyl group was achieved by allylic oxidation followed by hydrogenation of the Δ⁵ olefin and reduction of the 7-keto group with K-selectride. The polyamine side chain was introduced via reductive amination of an appropriately functionalized 3-keto steroid with a suitably protected spermidine utilizing sodium cyanoborohydride as the reducing agent. The required 24-sulfate was introduced by selective sulfation of the 7α,24ξ-diol with sulfur trioxide-pyridine complex.