Recent Advances in the Synthesis of Spermine and Spermidine Analogs of the Shark Aminosterol Squalamine

Abstract

Great attention has recently been focused on the shark aminosterol squalamine (1) because of its important antimicrobial and antiangiogenic activities. Herein, we present the different series of spermine and spermidine analogs that have been synthesized. Many of the squalamine mimics demonstrate a broad spectrum activity against microorganisms. Squalamine is currently undergoing Phase II clinical trials in cancer patients. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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

“…The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI). The antimicrobial activity of aminosterols (43)(44)(45)(46)(47)(48) and squalamine (1) Great efforts have also been made to synthesize squalamine. Okumura et al synthesized squalamine from a derivative of desmosterol via 12 steps with 7.4% of the total yield [38].…”

“…Jones et al described a practical synthesis of squalamine from stigmasterol in 15 steps [41,42]. An excellent review of methods for the synthesis of spermine and spermidine analogues of squalamine is made by Brunel and Letourneux [43]. They reviewed the synthesis of squalamine from cholestane and dinorcholenic acid and described its biological activity and clinical perspectives.…”

“…In turn, Rao and co-workers isolated six other aminosterols (43)(44)(45)(46)(47)(48) from the liver of the dogfish shark ( Figure 4) [15]. The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI).…”

“…The authors presented a very accurate spectral analysis based on 2D NMR (COSY, HETCOR, HMBC) as well as low-and high-resolution mass spectra (FAB, ESI, MALDI). The antimicrobial activity of aminosterols (43)(44)(45)(46)(47)(48) and squalamine (1) is summarized in Synthesis of 6β-hydroxy-3-α-(or β-)aminosterols (53-58) from hyodeoxycholic acid (49) has been presented by Jones et al (Scheme 3) [44]. The modification of hyodeoxycholic acid was carried out by the esterification of the carboxyl group and oxidation of both hydroxyl groups to ketones, followed by a conversion of the A/B ring system from cis to trans by acid-catalyzed isomerization.…”

Enantioselective Hydrogenation of C=N Functions and Enamines

“…and enamines to obtain the corresponding chiral amines still represents a major challenge. Whereas many highly enantioselective chiral catalysts have been developed for the asymmetric hydrogenation of alkenes and ketones bearing various functional groups, much fewer catalysts are effective for the hydrogenation of substrates with a C = N function (for pertinent recent reviews, see [12][13][14][15][16][17]). There are several reasons that might explain this situation.…”