A facile and general synthesis of 2b-aminosteroids in high yields from 2,3a-epoxy-5a-androstan-17-one by regioselective aminolysis is developed using a zinc chloride/water catalytic system. The reaction is successful with both aliphatic and aromatic amines as well as with azoles.Aminosteroids are pharmaceutically important compounds that display a broad spectrum of biological activity. A series of 2b-morpholinyl steroids has been shown to possess anesthetic activity and several examples have been selected for development as potential water-soluble steroidal intravenous anesthetics. 1 A steroid possessing a 2b-methylpiperazine moiety was reported to inhibit the proliferation of HL-60 or WEHI-3B cell lines and is a promising potential new drug for treatment of leukemia. 2 The rigid steroid skeleton, substituted with amino groups at different positions, provides an excellent means of studying structure-activity relationships within a series of neuromuscular blocking (NMB) agents. 3 These studies, carried out over the last forty years, have been very successful in producing highly active and selective drugs such as pancuronium, pipecuronium, vecuronium and rocuronium which are widely used in clinical practice. Another example, SZ-1677, which is related to rocuronium, is in the preclinical phase. These NMB agents have two acetylcholine-like (ACh-like) structural units located at the C-2 position of the A-ring and the C-16 position of the D-ring of the steroid. From many examples, it is clear that the D-ring ACh mimic is the NMB pharmacophore whereas the A-ring ACh moiety has muscarinic effects. 3c The muscarinic action generally results in undesirable side-effects. Bronchospasm side-effects forced the withdrawal of rapacuronium shortly after its clinical introduction in the United States despite its rapid onset and short duration of action. 4 As demonstrated with rapacuronium, the important biological effects of the 2b-amino moiety on the steroid A-ring have encouraged medicinal chemists to synthesize and test a large number of novel molecules. Considering that the inclusion of different amino groups at the 2b-position of the steroid skeleton is an important synthetic strategy in drug discovery, we have prepared a number of 2b-aminosteroid derivatives.An attractive route for the synthesis of 2b-aminosteroids involves direct aminolysis of an epoxide. Ring-opening of epoxides is a practical and widely used method for the synthesis of b-amino alcohols. 5 The synthesis of optically pure epoxides from the corresponding alkenes is easy to accomplish. 6 We were therefore interested in the ringopening of steroidal epoxide 1 with various amines in order to prepare axial 2b-aminosteroids of type 2 (Scheme 1). The most common method for the synthesis of compounds 2 involves treatment of steroidal epoxides with amines while heating in the presence of a catalytic amount of water. 2c,3a,7 1,2-Ethanediol has been used as the solvent for the synthesis of 2-alkylamino-3-ol derivatives. 1d,8 Ionic liquids have been used both as sol...
A new acylated flavone glycoside, skullcapflavone I 2′-O-β-D-(6′′-E-cinnamoyl) glucopyranoside (1), together with two known flavones, 5,2′-dihydroxy-7-methoxyflavone (2) and 5,2′,6′-trihydroxy-7-methoxyflavone-2′-O-β-D-glucopyranoside (3), and two known labdane diterpenoids, 14-deoxy-11,12-didehydroandrographolide (4) and andrographolide (5) were isolated from the whole plant of Andrographis nallamalayana. Structural elucidation of the new compound, as well as of the known compounds was achieved by various NMR techniques including 1 H-1 H COSY, HSQC, HMBC and ROESY experiments, ESITOF mass spectrometry, acid hydrolysis and saponification studies.
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