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The methods of synthesis as well as physical, spectroscopic (1H-NMR, 13C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological properties (PASS). Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

The title compound was synthesized from 3β-acetoxy-5-cholenic acid ( 2 ) in 17 steps.

Squalamine dessulfate (24 R ) and the unnatural product squalamine dessulfate (24 S ) have been synthesized from stigmasterol. The key step in establishing the C24 stereochemistry is attachment of the sidechain at C22 using either (2 R )- or (2 S )-1,2-epoxy-3-methylbutane to yield the cholesteryl precursors of the epimeric squalamine dessulfates.

The synthesis and conversion of a new spermidine equivalent ( 2 ) to squalamine is reported. It is prepared in a practical manner, is stable to sodium borohydride reduction, is converted to spermidine under mild conditions, and is not prone to internal cyclization reactions.

A new highly stereoselective construction of the sidechain of squalamine has been achieved by using methyl-3-keto-5α-chenodeoxycholanate ( 2 ) as the starting material and an improved Sharpless catalytic asymmetric dihydroxylation as the key step.

A series of 3-amino and polyaminosterol analogues of squalamine and trodusquemine were synthesized involving a new stereoselective titanium reductive amination reaction in high chemical yields of up to 95% in numerous cases. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. Activity was highly dependent on the different compounds' structures involved and best results have been obtained with aminosterol derivatives 4b , 4e and 6i exhibiting activities against yeasts, Gram positive and Gram negative bacteria at average concentrations of 6.25–12.5 μg/mL.

The discovery of two new components of the migratory pheromone used by sea lamprey to guide adults to spawning grounds was recently reported. These hold promise for use in a pheromone-based control program for this species, an invasive pest in the Great Lakes. Details of the structure determination of these steroidal bis-sulfates [petromyzosterol disulfate (PSDS, 2) and petromyzonamine disulfate (PADS, 3)] are described here. Pattern matching of 1H NMR data was particularly valuable. This involved comparison of spectra of the natural samples of 2 and 3 with those of appropriate steroidal analogues [e.g., petromyzonol sulfate (PS, 1, a previously known sea lamprey bile acid derivative that is a third component of the migratory pheromone), cholesterol sulfate (6), and squalamine (8)] and model compounds containing the unprecedented aminolactam substructure present in 3. The logic underlying the iterative analyses used is presented.

[reaction: see text] A short and highly stereoselective synthesis of the novel steroid squalamine (1) was accomplished in nine steps from easily available methyl chenodeoxylcholanate 2. Our synthesis featured improved dehydrogenation of 4 followed by conjugate reduction to construct the trans AB-ring system and efficient asymmetric isopropylation of aldehyde 6 to introduce the C-24R-hydroxyl group.

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.

This paper concerns the synthesis of various simplified analogues of the novel anti-microbial agent, squalamine. The compounds were then investigated for activity against Trypanosoma brucei, the causative agent of African trypanosomiasis, Trypanosoma cruzi, the causative agent of Chagas disease and Leishmania donovani, the causative agent of visceral leishmaniasis. Several compounds showed in vitro activity, especially against T. brucei and L. donovani. However, one compound showed poor in vivo activity.