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Page 30 of 50 Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02

Figure 50. Microbial transformation of ethisterone (277) Cunninghamella blakesleeana,Cunninghamella elegans and Macrophomina
phaseolina.

niger yielded a new metabolite, 17α-ethynyl-6α, 17β-dihydroxyandrost-4-en-3-one (281) (0.60%), along with
[73]
the known metabolite, 17α-ethynyl-11α, 17β-dihydroxyandrost-4-en-3-one (282) (0.30%) [Figure 50].

Two new derivatives, 17α-ethyl-11α, 17β-dihydroxyandrost-4-en-3-one (284) (0.80%), and 17α-ethyl-6α, 17β
-dihydroxy-5α-androstan-3-one (285) (60.0%) were also synthesized through the biotransformation of 17α-
ethyl-17β-hydroxyandrost-4-en-3-one (283) with C. elegans [Figure 51]. Derivatives 278 (IC = 5.95 ±
[72]
50
0.00078 μM), 284 (IC = 3.46 ± 0.01046 μM), and 285 (IC = 1.72 ± 0.00089 μM) showed remarkable
50
50
tyrosinase inhibitory activity, as compared to the substrates 277 (IC = 2.61 ± 0.037328 μM), 283 (IC = 1.53
50
50
± 0.001088 μM) . Tyrosinase is an enzyme involved in the melanin biosynthesis; therefore, its inhibitors are
[72]
used in the prevention of excessive production dermal melanin.
Biotransformation of mestranol (286)
Biotransformation of an oral steroidal contraceptive drug, mestranol (286), with the fungal culture of
Cunninghamella elegans afforded a new compound, 6β, 12β-dihydroxymestranol (287) (3.6%), and the
known derivative, 6β-hydroxymestranol (288) (2.7%) [Figure 52].
[74]
Biotransformation of methyloestrenolone (289)
Six transformed products, 17α-methyl-6β,17β-dihydroxyestr-4-en-3-one (290) (1.8%), 17α-methyl-11β, 17β,
20-trihydroxyestr-4-en-3-one (291) (0.8%), 17α-methyl-2α, 11β, 17β-trihydroxyestr-4-en-3-one (292) (0.6%),
17α-methyl-1β, 17β-dihydroxyestr-4-en-3-one (293) (4.5%), 17α-methyl-11α, 17β-dihydroxyestr-4-en-3-one
(294) (0.45%), and 17α-methyl-11β, 17β-dihydroxyestr-4-en-3-one (295) (1.4%) were synthesized via
biotransformation of a steroidal contraceptive drug, methyloestrenolone (289) with Macrophomina
[75]
phaseolina. Compounds 290-295 were found to be new compounds [Figure 53]. Two known derivatives,
17α-methyl-10β, 17β-dihydroxyestr-4-en-3-one (296) (0.8%), and 17α-methyl-17β, 20-dihydroxyestr-4-en-3-
[75]
one (297) (1.2%) were obtained through biocatalysis of 289 with Aspergillus niger [Figure 54].

Biotransformation of drospirenone (298)
Drospirenone (298) is an orally active contraceptive drug, marketed under the brands Sylnd and Yasmin.
Cunninghamella elegans-catalyzed transformation of drospirenone (298) afforded four new metabolites, 6β,