Abstract
The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum—a fungal species not used in biotransformations so far—were described. All the substrates were converted in high yield (70%–99%) into d ring δ-lactones. The oxidation of 1 produced 3α-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (5). The oxidation of 2 led to 3β-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (6). The biotransformation of 3 resulted in the formation of 3α-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (5) and 17a-oxa-d-homo-5α-androstan-3,17-dione (7). An analysis of the transformation progress of the studied substrates as a function of time indicates that the Baeyer-Villiger monooxygenase of this fungus does not accept the 3β-hydroxy-5-ene functionality of steroids. In this microorganism steroidal 3β-hydroxy-dehydrogenase (3β-HSD) was active, and as a result DHEA (4) was transformed exclusively to testololactone (8). Apart from the observed oxidative transformations, a reductive pathway was revealed with the C-3 ketone being reduced to a C-3α-alcohol. It is demonstrated for the first time that the reduction of the 3-keto group of the steroid nucleus can occur in the presence of a ring-D lactone functionality.
Highlights
IntroductionSteroids represent an important class of natural products with varying pharmacological properties
Steroids represent an important class of natural products with varying pharmacological properties.Minor modifications in their structure may affect their bioactivity, research on the preparation of potentially useful steroid analogues is being continued for development of processes exploitable by the pharmaceutical industry
The P. lanosocoeruleum KCH 3012 strain produces a Baeyer-Villiger monooxygenase which is able to carry out the regioselective ring-D lactonization of 5α-dihydro-steroids (1–3) as well as unsaturated steroid 4 (Scheme 1, Table 1)
Summary
Steroids represent an important class of natural products with varying pharmacological properties. Cyclopentadecanone monooxygenase (CPDMO) isolated from Pseudomonas sp., involved in the catabolism of cyclopentadecanone in Nature, was found to accept steroids as substrates [3] It has been screened for the Baeyer-Villiger oxidation of a large number of steroids but the products were formed in low yields. Penicillium citreo-viride oxidized androstenedione, progesterone and DHEA (dehydroepiandrosterone) to testololactone, while pregnenolone was not transformed; conversion of DHEA to testololactone occurred through the 3β-hydroxysteroid dehydrogenase/5-ene-4ene isomerase pathway resulting in the generation of a 4-en-3-oxo system in the steroid ring-A [7]. This same pathway was observed during the transformation of DHEA by P. griseopurpureum and. To the best of the author’s knowledge, this is the first report of the use of P. lanosocoeruleum in biotransformations
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