Biotransformations of the cardiovascular drugs mexrenone and canrenone.
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.
Preisig
Carol L
CL
MDS Pharma Services, 11804 North Creek Parkway South, Bothell, Washington 98011, USA. cpreisig@diversa.com
Laakso
Jodi A
JA
Mocek
Ursula M
UM
Wang
Ping T
PT
Baez
Julio
J
Byng
Graham
G
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
D002317:Cardiovascular Agents; D013148:Spironolactone; C019225:SC 25152; D002192:Canrenone