A Short Formal Synthesis of Squalamine from a Microbial Metabolite

Abstract

A short formal synthesis of squalamine is described, utilizing the biotransformation product 2, which is available in one step from commercially available 3-keto-23,24-bisnorchol-4-en-22-ol (1). Regioselective C-22 oxidation and C-24 sulfation of the corresponding alcohols in the presence of a free C-7 alcohol make for an efficient preparation of squalamine intermediate 11.

Formal Synthesis of Squalamine from Desmosterol

“…[8][9][10] Very recently, a dramatically shortened synthetic route (10 steps) via microbial 7a-hydroxylation of 22-hydroxy-23,24-bisnorchol-4-en-3-one was reported. 11) Other groups also developed their own synthetic route of squalamine. Kim and coworkers prepared it from 22-hydroxy-23,24-bisnorchol-4-en-3-one, via 12 steps.…”

Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies

“…The conjugate (17), which is similar to (24)(25)(26) with the exception of the functional group at position C(7), has comparable antimicrobial activity to (25). Both compounds were much more active than the compounds (24) and (26). All synthesized conjugates (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) (Figure 2) [33].…”

“…Both compounds were much more active than the compounds (24) and (26). All synthesized conjugates (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) (Figure 2) [33]. The multistep reactions gave final products with very good yields.…”

“…However 3β-spermine-23,24-bisnor-5β-cholane (23) exhibits the highest biological activity among all the compounds (16)(17)(18)(19)(20)(21)(22)(23). The conjugate (17), which is similar to (24)(25)(26) with the exception of the functional group at position C(7), has comparable antimicrobial activity to (25). Both compounds were much more active than the compounds (24) and (26).…”

“…This aminosterol is a novel broad-spectrum antibiotic and exhibits a biocidal activity against Gram-positive and Gram-negative bacteria, fungi, protozoa, and viruses [15][16][17][18][19][20][21][22][23]. The antimicrobial activity of the squalamine has inspired work to design and synthesize new derivatives of steroidal-polyamine conjugates [24][25][26][27][28][29][30][31][32]. …”