Biotransformation into 11α-hydroxyprogesterone glucosides by glucosyltransferase

Abstract

ABSTRACT Recently, studies on the steroidal hormone activity in the brain have attracted attention, and the influences of the varied glucosides and their artificial derivatives have been discussed; additionally, it has been suggested that glucosides are the synthetic precursors of glucuronide as a label molecule. However, glucosides are formed with 11&agr;‐hydroxyprogesterone (1), which is important as a blood pressure regulator, but anti‐androgen activity remains unknown. Using UDP‐glucosyltransferase, glucoside synthesis was successful in linking &bgr;‐d‐glucopyranose and &bgr;‐d‐laminaribiose to 11&agr; oxygen of 1 at a high conversion ratio, and full assignment structure was analyzed for the two glucosides by high‐resolution quadrupole‐time flight electrospray ionization‐mass spectrometry, 1D (1H and 13C) NMR and 2D (COSY, ROESY, HSQC‐DEPT and HMQC) NMR. Furthermore, the bioactivity of 1 and two 11&agr;‐hydroxyprogesterone glucosides [11&agr;‐(&bgr;‐d‐glucopyranosyl)oxyprogesterone, 2, and 11&agr;‐(&bgr;‐d‐laminaribiosyl)oxyprogesterone, 3] was tested in vitro. On rotenone‐induced PC12 cells, the two 11&agr;‐hydroxyprogesterone glucosides (2 and 3) showed superior neuroprotective effects and increased cellular ATP levels compared with those of 1.