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Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02 Page 11 of 50

Figure 16. Microbial transformation of (-)-ambrox (64) with Actinidia deliciosa, and Macrophomina phaseolina.

Moreover, biotransformation of (-)-ambrox (64) with Macrophomina phaseolina afforded a new compound,
1α-hydroxy-3-oxoambrox (75) (3.5%), along with four known compounds 70, and 72-74 [Figure 16].
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Three more derivatives, 69, ambrox-2α-ol (76) (2.5%), and ambrox-2α,3β-diol (77) (3%), were also
synthesized through biotransformation of (-)-ambrox (64) by using cell suspension culture of plant
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Peganum harmala [Figure 17]. Some of the resulting metabolites exhibited exotic aroma, different from
the substrate 64.

Biotransformation of artemether (78)
Biotransformation of an anti-malarial sesquiterpenoid drug artemether (78) with plant cell suspension
culture of Azadirachta indica afforded two derivatives, 9α-acetoxy, 10β-methoxyartemethin (79) (1.2%), and
3α-hydroxy, 12β-methoxyartemethin (80) (2.5%) [Figure 18]. Three derivatives 79, 80, and 3α-12β-
dihydroxyartemethin (81) (3.5%) were obtained from Macrophomina-phaseolina-mediated transformation
of 78 [Figure 18] [Supplementary Figure 4]. In addition, two new derivatives, peroxy-linkage, 9α-
hydroxyartemethin (82) (2.8%), and 10β-hydroxyartemethin (83) (4.6%), were obtained via the
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biotransformation of artemether (78) with Fusarium lini [Figure 18] [Supplementary Figure 4].
Compounds 79-83 showed no anti-malarial activity (Plasmodium falciparum, 3D7 strain) in vitro.

Biotransformation of sclareolide (84)
Curvularia lunata-catalyzed transformation of a sesquiterpene lactone sclareolide (84) afforded a new
derivative, 1α, 3β-dihydroxysclareolide (85) (16%), along with four derivatives, 3-ketosclareolide (86) (8.7%),
1β-hydroxysclareolide (87) (9.3%), 3β-hydroxysclareolide (88) (12.2%), and 1β,3β-dihydroxysclareolide (89)
(7%). Biotransformation of 84 with Aspergillus niger also yielded metabolites 85-89. Transformed products
85-88 were also obtained by the transformation of 84 with Gibberella fujikuroii, while fermentation of 84
with Fusarium lini produced metabolites 87 and 88 [Figure 19]. Similarly, biotransformation of
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sclareolide (84) with Cunninghamella elegans afforded six derivatives 86, 88, 89, 2α-hydroxysclareolide (90)
(5.3%), 2α, 3β-dihydroxysclareolide (91) (23.6%), 1α, 3β-dihydroxysclareolide (92) (2.7%), and 3β-hydroxy-8-
episclareolide (93) (1.3%) [Figure 20]. Structural transformations in derivatives 86 (100%), 88 (87.5%), 89
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(72.3%), 90 (82.7%), and 92 (75%) have increased their phytotoxicity against Lemna minor L., in comparison
to the substrate 84 (62.5%), while derivative 91 (50%) showed weak phytotoxicity at 100 μg/mL.

Biotransformation of (-)-guaiol (94)
Biotransformation of a sesquiterpene (-)-guaiol (94) with Rhizopus stolonifer afforded a new compound, 1-
guaiene-9α,11-diol (95) (1.6%) [Figure 21]. Similarly, Cunninghamella elegans-assisted transformation of 94
yielded compounds, 1-guaiene-3α,11-diol (96) (1.8%), and 1(5)-guaiene-3α,9,11-triol (97) (1.8%)