Transformation of Progesterone and Related Steroids by Aspergillus tamarii

Abstract

Vol. 30 acid (XIV). The analytical sample was purified by four recrystallizations from acetone: m.p. 192-194°14; t.l.c., ethyl acetate-acetone-methanol (3:3:1). Mixture melting point and infrared (KBr) were coincident with an authentic specimen.

Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus tamarii KITA: transformation of a series of cortical steroid analogues

“…Frequently [2] it has not been possible to isolate testosterone acetate (2); this has been explained by the presence of high levels of the esterase enzyme [2] resulting in rapid hydrolysis of the acetate. A minor hydroxylation pathway is also present in this organism, here testosterone is hydroxylated at the 11␤-position [1] with no further metabolism observed [9].…”

“…The 1 H NMR spectrum of the next metabolite isolated was devoid of the 21-methyl signal (δ H 2.28 ppm) present in the starting material suggesting loss of the cortical side chain. This was fully supported by loss of signals at δ C 211.6 and 27.8 ppm in the 13 C NMR spectrum of the starting material assigned to C-20 and C-21 and a downfield shift of the C-13 resonance signal of δ C 35.4 ppm consistent with insertion of oxygen adjacent to this position on ring D. This coupled with the upfield shift in the 18-methyl resonance signal of δ H 0.61 ppm and a new quaternary resonance signal at δ C 171.9 ppm were consistent with lactone formation [14] all other spectral data were consistent with the structure of testololactone (5) as was the melting point 208 • C following crystallisation from ethyl acetate in light petroleum as needles lit., 208 • C [1,9] (found: 302.187 C 19 H 26 O 3 requires 302.188). The final transformation product was identified as 17␣-oxa-d-homo-androst-1,4-diene-3,17-dione (12).…”

“…A variety of fungi [1][2][3][4][5][6][7] have been identified which can stereospecifically degrade the 17␤-acetyl side chain of progesterone in high yield to give the ring D steroidal lactone testololactone (5). Of these fungi Aspergillus tamarii KITA is the most efficient, with yields from transformation reported at 70% [1].…”

“…Of these fungi Aspergillus tamarii KITA is the most efficient, with yields from transformation reported at 70% [1].…”

“…The pathway initiates with a selective Baeyer-Villiger oxidation of the cortical side-chain producing testosterone acetate (2), this is then hydrolysed to form testosterone (3) oxidation of which follows giving androst-4-en-3,17-dione (4) this then undergoes a ring D Baeyer-Villiger oxidation yielding testololactone (5). In a number of reports the (20(R)) analogue of progesterone (6) has been isolated [8] and it has been suggested that a competitive equilibrium exists between the reductase forming the alcohol (6) and the oxidase that regenerates (1). Frequently [2] it has not been possible to isolate testosterone acetate (2); this has been explained by the presence of high levels of the esterase enzyme [2] resulting in rapid hydrolysis of the acetate.…”