Formal Synthesis of Squalamine from Desmosterol

Abstract

The key intermediate to squalamine, (5a a,7a a,24R)-7,24-dihydroxy-cholestan-3-one, was synthesized from the 3-O-acetyl-24R,25-dihydroxy derivative of desmosterol via 10 steps in 16% overall yield and squalamine was also prepared via two further steps in 7.4% total yield from the desmosterol derivative.

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

“…All synthesized conjugates (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) exhibited very good activity against Gram-positive bacteria. The synthesis of a series of 7-fluoro-3-aminosteroids (36)(37)(38)(39)(40)(41)(42) is shown in Scheme 2 [37]. These compounds demonstrate a high antimicrobial activity, especially against Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Escherichia coli ( Table 1).…”

“…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]. Moriarty and co-workers synthesized (1) from 3β-acetoxy-5-cholenic acid by 17 steps [39,40].…”

Steroidal Conjugates and Their Pharmacological Applications

“…A short review on synthesis of spermine and spermidine analogs of shark aminosterol squalamine has been reported [15]. Formal synthesis of squalamine has been achieved in twelve steps from desmosterol with 7.4 % overall yield by Takeuchi and co-workers [16]. Recently Zhou et al have accomplished a concise and stereoselective synthesis of squalamine from easily available chenodeoxycholate [17].…”

A Short and Highly Stereoselective Synthesis of Squalamine from Methyl Chenodeoxycholanate

“…9 Very recently, a new formal synthesis of squalamine from desmosterol was also reported. 10 In our previous communication, 11 we described a short (9 steps) and highly stereoselective synthesis of squalamine via improved IBX-mediated dehydrogenation and asymmetric isopropylation from easily available methyl chenodeoxycholanate. Herein, we wish to describe the details and some new improvements regarding the synthesis of the target compound.…”