A Short and Highly Stereoselective Synthesis of Squalamine from Methyl Chenodeoxycholanate

Abstract

A short and highly stereoselective synthesis of squalamine (1) was accomplished in 9 steps from easily available methyl chenodeoxycholanate (2). The advanced intermediate 7α,24R-dihydroxy-cholestan-3-one (9) was synthesized by using improved dehydrogenation of 4 followed by conjugate reduction and efficient asymmetric isopropylation of aldehyde 7 as key reactions. Reagents and conditions: (a) Ag2CO3 on celite, toluene, reflux, 92%; (b) MOMCl, i-Pr2NEt, cat. NaI, CH2Cl2, reflux, 91%; (c) 2.0 equiv. of IBX, 30 mol% of TFA, DMSO, r.t, 24 h, 87%.

The Reaction Kinetics of Aluminum and Isopropanol

“…Wislicenus and Kaufman synthesized aluminum alkoxide from aluminum amalgam in overdosed refluxing alcohol in 1893. Hillyer synthesized aluminum alkoxide from aluminum and alcohol by using SnCl 4 as catalyst in 1897 [1]. Aluminum isopropoxide has already been the important precursor of high-tech materials and functional nanomaterials, and it also has new application in the markets of new luminescent materials and high purity ultrafine Al 2 O 3 powders [2] , etc.…”