Page 95 - Read Online

Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02 Page 41 of 50

[88]
3,17-dione (386) (2.04%), and 11α, 15β-dihydroxypreg-4-ene-3, 20-dione (387) (2.30%) [Figure 71].

Biotransformation 6-dehydroprogesterone (388)
6-Dehydroprogesterone (388) is a synthetic derivative of progesterone hormone. Biotransformation of 6-
dehydroprogesterone (388) with the fungal cell culture of Aspergillus niger afforded three new metabolites, 6
β-chloro-7α, 11α-dihydroxypregna-4-ene-3, 20-dione (389) (1.0%), 7α-chloro-6β, 11α-dihydroxypregna-4-
ene-3,20-dione (390) (1.33%), and 6α, 7α-epoxy-11α-hydroxypregna-4-ene-3,20-dione (391) (1.33%), along
with the two known metabolites, 6α, 7α-epoxypregna-4-ene-3,20-dione (392) (2.0%), and 11α-
[89]
hydroxypregna-4, 6-diene-3,20-dione (393) (2.33%) [Figure 72]. Whereas, Gibberella fujikuroi-catalyzed
transformation of substrate 388 yielded the known compound, 11α, 17β-dihydroxyandrosta-4, 6-dien-3-one
[89]
(394) (15.4%) [Figure 73].
Biotransformation 20-hydroxymethylpregna-1,4-dien-3-one (395)
(20S)-20-Hydroxymethylpregna-1, 4-dien-3-one (395) is another neurochemical, which is obtained by
microbial-catalyzed degradation of sterols. Compound 395 is also used as an intermediate in the synthesis of
many steroid-based drugs. Six new metabolites, 11α-hydroxy-20- acetoxymethylpregna-1,4-dien-3-one (
396) (0.40%), 17α-hydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (397) (0.46%), 6β, 11α-dihydroxy-20-
hydroxymethyl pregna-1, 4-dien-3-one (398) (0.60%), 11α, 15β-dihydroxy-20-hydroxymethylpregna-1, 4-
dien-3-one (399) (2.0%), 11α, 17α-dihydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (400) (0.40%), 14α,
15β, 17α-trihydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (401) (0.40%), along with the known
metabolite, 11α-hydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (402) (8.66%), were synthesized through
the biotransformation of 20-hydroxymethylpregna-1, 4-dien-3-one (395) with Cunninghamella elegans
[90]
[Figure 74]. Three new derivatives, 15β-hydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (403) (1.12%), 7β
-hydroxy-20-hydroxymethylpregna-1, 4-dien-3-one (404) (0.62%), and 7β, 15β-dihydroxy-20-
hydroxymethylpregna-1, 4-dien-3-one (405) (8.70%), were also synthesized by Macrophomina phaseolina-
[90]
catalyzed transformation of compound 395 [Figure 75].
Biotransformation ganaxolone (407)
Ganaxolone (407) is a synthetic steroidal-based anti-epileptic drug (CCD-1042) under development by
Marinus Pharmaceuticals. Compound 407 is a 3β-methylated derivative of allopregnanolone (neurosteroid).
The new metabolite, 14α-hydroxy-5α-pregnan-1-ene-3, 20-dione (408) (1.30%), along with the four known
metabolites, 11α-hydroxy-pregn-1, 4-diene-3,20-dione (409) (2.87%), 6β, 11α-dihydroxy-pregn-4-ene-3, 20-
dione (410) (4.66%), 5α-pregnan-3, 20-dione (411) (4.56%), and 5α-pregnan-4-ene-3, 20-dione (412) (5.46%)
[60] [Figure 76]. Ganaxolone (407) showed good aromatase inhibitory activity (IC = 13.76 ± 2.00 µM), while
50
its derivatives were found to be inactive.

BIOTRANSFORMATION OF STEROIDAL ALKALOID
Biotransformation of dictyophlebine (413)
The new compound, 3β-(propyloxycarbonylamino)-dictyophlebin-16-ene (414) (0.55%), along with the two
known derivatives, 5, 6-dihydrosarconidine (415) (0.52%) and iso-N-formylchonemorphine (416) (0.54%),
were synthesized through the biotransformation of the steroidal alkaloid, dictyophlebine (413)
[91]
[Figure 77]. The new derivative 414 was found to be the potent inhibitor of acetyl-, and
butyrylcholinesterase enzymes with the IC values of 2.2 and 1.2 μM, respectively, as compared to the
50
standard drug, galanthamine (IC 0.5 and 8.2 μM for AChE and BChE, respectively).
50

BIOLOGICAL ACTIVITY EVALUATION OF TRANSFORMED PRODUCTS
Fully characterized derivatives were evaluated through various cell-based and biochemical assays. Bio-
catalytic structural changes in natural/synthetic compounds of various classes have affected their biological