Rapid Construction of a Squalamine Mimic

摘要

Squalamine is a novel sterol—spermidine conjugate that has recently been isolated from tissues of the dogfish shark, Squalus acanthias. This unusual natural product has attracted considerable interest because of its potent antimicrobial activity against a broad spectrum of microorganisms. At present, the feasibility of obtaining large quantities of this steroidal antibiotic from natural sources appears questionable; only trace amounts are present in the liver and gallbladder of the shark. While a recent synthesis has confirmed the structure of squalamine, the 17 steps that are needed, together with a low overall yield (0.36%) and expensive starting material (3β-acetoxy-5-cholenic acid), make such a route impractical for large-scale preparations.