title: Biotransformations of the cardiovascular drugs mexrenone and canrenone.
abstract: Microbial transformation studies of the cardiovascular drugs mexrenone (1) and canrenone (2) were conducted. Thirty-nine biotransformations of mexrenone and 84 biotransformations of canrenone were analyzed. Metabolism of the substrate was observed in the majority of these cases. Several monohydroxylated derivatives were detected by HPLC-MS-UV and subsequently identified. Two new mexrenone derivatives, 11alpha- (3) and 12beta-hydroxymexrenone (4), and the known metabolite 6beta-hydroxymexrenone (5) were isolated as major products produced by the Beauveria bassiana ATCC 13144 bioconversion (3) and the Mortierella isabellina bioconversion (4 and 5), respectively. Single-elimination products were also sought; however, only the production of the known metabolite Delta(1,2)-mexrenone (6) by several bacteria was confirmed. One new monohydroxylated derivative of canrenone, 9alpha-hydroxycanrenone (7), was isolated as a major product from the Corynespora cassiicola bioconversion. Structure elucidation of all metabolites was based on NMR and HRMS analyses.
authors.affiliation: MDS Pharma Services, 11804 North Creek Parkway South, Bothell, Washington 98011, USA. cpreisig@diversa.com
authors.forename: Carol L
authors.initials: CL
authors.lastname: Preisig
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Laakso
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Mocek
authors.forename: Ping T
authors.initials: PT
authors.lastname: Wang
authors.forename: Julio
authors.initials: J
authors.lastname: Baez
authors.forename: Graham
authors.initials: G
authors.lastname: Byng
mesh_terms: D001711:Biotransformation; D002192:Canrenone / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D005658:Fungi / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D020094:Mortierella / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D002317:Cardiovascular Agents; D013148:Spironolactone; C019225:SC 25152; D002192:Canrenone