Stereoselective synthesis of 24-hydroxylated compounds useful for the preparation of aminosterols, vitamin D analogs, and other compounds

• Main Authors: Kinney, William A, Jones, Steven, Zhang, Xuehai, Rao, Meena N, Bulliard, Michel, Meckler, Harold, Lee, Nancy
• Format: Patent
• Language: English
• Published: 26.08.2003

Several aminosterol compositions have been isolated from the liver of the dogfish shark, . One important aminosterol is squalamine (3 -(N-[3-aminopropyl]-1,4-butanediamine)-7 ,24 -dihydroxy-5 -cholestane 24-sulfate), the chemical structure of which is shown in FIG. . This aminosterol, which includes a sulfate group at the C-24 position, is the subject of U.S. Pat. No. 5,192,756 to Zasloff, et al., which patent is entirely incorporated herein by reference. This patent describes antibiotic properties of squalamine. A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.