c
J. Chem. Sci. Vol. 127, No. 10, October 2015, pp. 1827–1830. ꢀ Indian Academy of Sciences.
DOI 10.1007/s12039-015-0950-7
Chemical methods for the conversion of Prednisolone
to 11-β-hydroxy-1,4-androstadiene-3,17-dione
PINNAMA REDDY SURYA PRATAPa, SYED SHAFIb,∗, FATIMA NAAZc
and NAYAKANTI DEVANNAa
aDepartment of Industrial Chemistry, Jawaharlal Nehru Technological University, Anantapur, India
bDepartment of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India
cDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New
Delhi 110 062, India
e-mail: syedshafi@jamiahamdard.ac.in; shafirrl@gmail.com
MS received 21 May 2015; revised 14 July 2015; accepted 22 July 2015
Abstract. Several microbial transformations of steroids to 17-keto cortisones through side chain cleavage
have been presented in the literature; however, yields and product selectivity in these methods were low. In
the present study, some new methods have been identified for the side chain cleavage of prednisolone (1) to
form 11-β-hydroxy-1,4-androstadiene-3,17-dione (11-β-hydroxy ADD). Prednisolone upon reaction with zinc
chloride in dry THF results in the formation of cleavage product in good yield (76%). 11-β-hydroxy ADD (2)
has been formed in moderate yield (60%) under the Reformatsky reaction conditions by reacting with zincate.
While performing the Wittig reaction using stable ylides, again results in the formation of compound 2 in good
yield (56%). Side chain cleavage of prednisolone was confirmed from the physical and analytical data and
similar when compared with the literature reports.
Keywords. Prednisolone; 11-β-hydroxy-1,4-androstadiene-3,17-dione; Chemical methods; ZnCl2; Stable
Wittig ylide; Reformatsky reaction
1. Introduction
of bioactive molecules. Androstadienedione (ADD)
is one of that important 17-keto cortisones that has
served as a key synthon for the development of several
bioactive molecules. ADD is an important precursor for
the production of sex hormones such as testosterone,
estrogen, estrone and ethinyl estradiol.3,5,6
Androstadienedione (1,4-androstadiene-3,17-dione)
is a next generation orally active prohormone. It is
a direct precursor to the anabolic steroid boldenone.
Boldenone is an anabolic steroid most often found in
injectable form as a veterinary medicine (boldenone
undecylenate). It is chemically a derivative of testoster-
one. Androstadienedione is used as a pharmaceutical
intermediate for further synthesis of female sex hor-
mones, in hormone replacement therapies and oral con-
traceptives.
Steroids like progesterone, testosteronedianabol, preg-
nenolone, cholesterol, sitosterol, stigmasterol, ergos-
terol, etc. have been reported to produce ADD through
bio-transformations.5–7 Progesterone is widely used as
an important precursor of androstadienedione (ADD).
Progesterone was biotransformed to ADD by Bacillus
sphaericus with the maximum yield of 22%.8 A major
problem in the biotransformation of steroid is the poor
solubility of substrates in aqueous solutions, which
Steroids play an important role in the hormonal balances.
Steroids are widely used as therapeutic agents and since
their inception in the market and research efforts have
been made to improve production processes as well
as to develop novel synthetic molecules with enhanced
efficiency and reduced side effects.
Microorganisms have been widely applied for the
biotransformation of steroids to generate functionalized
steroids over the years.1 These biotransformations lead
to the production of steroidal contraceptive hormones
and anti-inflammatory drugs from various precursors
such as steroids, phytosterols, sapogenins, etc.2 Bio-
transformations of steroids result in the formation of
variety of synthons which can be readily used for fur-
ther drug development.3 A number of microorganisms
have been utilized for steroid transformation including
varieties of bacteria, fungi, yeast and algae.4
Amongthese biotransformations and microbial trans-
formation, enzyme catalysed side chain cleavage of
steroids result in the formation of 17-keto cortisones.5,6
17-keto cortisones have a wide range of applications
including the semi-synthetic modifications for the synthesis
∗For correspondence
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