Synthesis of aminosterols structurally related to squalamine

Squalamine is a naturally occurring broad-spectrum antimicrobial agent isolated from the dogfish shark Squalus acanthias. It has been shown to have biological activity against both Gram-negative and Gram-positive bacteria, fungi, sexually transmitted diseases (STDs) and cancer. A flexible synthetic route to polyamine-steroid conjugates structurally related to squalamine has been developed.;Five different steroids and have been prepared, three of which have been combined with the protected polyamines shown below to give a large combinatorial library of aminosterols. (Fig. 8782A).;Reductive amination was used to combine the steroids with the protected polyamines, and putrescine. (Fig. 8782B).;Forty-four aminosterols were synthesised and are currently being tested for antimicrobial and anticancer activity.