Synthesis and Evaluation of Antimicrobial Properties of Amidinoazaandrostanes and Guanidinoazaandrostanes

• Published in: Journal of pharmaceutical sciences 1974-04, Vol.63 (4), p.620-622
• Main Authors: Doorenbos, Norman J., Kim, Jack C.
• Format: Article
• Language: English
• Subjects: 4-Amidino-17α-methyl-4-aza-5α-androstan-17β-ol and 4-(β-guanidinoethyl)-17α-methyl-4-aza-5α-androstan-17β-ol -synthesis; 4-Amidino-17α-methyl-4-aza-5α-androstan-17β-ol and 4-(β-guanidinoethyl)-17α-methyl-4-aza-5α-androstan-17β-ol —synthesis, antimicrobial activity; 4-Azasteroids-synthesis; 4-Azasteroids—synthesis, antimicrobial activity of amidino- and guanidinoazaandrostanes; Amidines - chemical synthesis; Amidines - pharmacology; Androstanes - chemical synthesis; Androstanes - pharmacology; antimicrobial activity; antimicrobial activity of amidino- and guanidinoazaandrostanes; Antimicrobial activity-4-amidino-17α-methyl-4-aza-5α-an-drostan-17β-ol and 4-(β-guanidinoethyl)-17α-methyl-4-aza-5α-androstan-17β-ol; Aza Compounds - chemical synthesis; Aza Compounds - pharmacology; Bacteria - drug effects; Guanidines - chemical synthesis; Guanidines - pharmacology; Microbial Sensitivity Tests; Saccharomyces cerevisiae - drug effects
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600630430

The intermediate, 17α-methyl-4-aza-5α-androstan-17β-ol (III) required for the synthesis of 4-amidino-17α-methyl-4-aza-5α-androstan-17β-ol (VII) and 4-(β-guanidinoethyl)-17α-methyl-4-aza-5α-androstan-17β-ol (VI) was obtained through a reaction of 17α-methyl-3,5-seco-4-norandrostan-17β-ol-5-on-3-oic acid with ammonium hydroxide followed by two reductions (platinum dioxide and lithium aluminum hydride). Condensation of III with chloroacetonitrile under anhydrous condition, followed by reduction of the nitrile with lithium aluminum hydride, gave 4-(β-aminoethyl)-17α-methyl-4-aza-5α-androstan-17β-ol (V). The reaction of V with 2-methyl-2-thiopseudourea sulfate and of III-hydrochloride with cyanamide provided the title compounds, VI-sulfate and VII-hydrochloride, respectively. A serial dilution assay showed the title compounds to have antimicrobial activity against Saccharomyces cerevisiae. This activity is especially significant since this is the greatest activity thus far obtained in a 4-azaandrostane with a hydroxyl group at the 17β-position.