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OJBTm
Online Journal of Bioinformatics©
Established 1995
ISSN 1443-2250
Volume 20(3): 233-244, 2019.
Alternate
synthesis of Finasteride and derivatives to inhibit 5α-reductase.
Divya Sanganabhatla and R Shyam Sunder.
Department
of Pharmacy, University College of Technology, Osmania University,
Hyderabad-500007, India
ABSTRACT
Sanganabhatla D, Sunder RS., Alternate synthesis of Finasteride and derivatives
to inhibit 5α-reductase,
20(3):
233-244, 2019. Finasteride is used to manage benign prostatic hyperplasia and
androgenic alopecia but currently its synthesis is a costly process. We synthesized
finasteride (3-oxo-4-aza-5α-androst-1-ene-17β-(N-tert-butylcarboxamide)
and its derivatives from 4-androsten-3,17-dione via 7
steps with an overall yield of 20%. Conditions of processing were optimized and
scaled by purification of each step by crystallization and recrystallization. At
1st step we obtained ~95% acid 3 compared with previously reported 88.8%
by using ~10% less sodium periodate. Hydrogenation
was optimized by using 0.2 weight equivalent of palladium carbon atmospheric
pressure at 25oC for 4 h to yield 78.2%. We used 2,3-dichloro-5,6-dicyanobenzoquinone
to synthesize large amounts of finasteride by re-crystallization of crude
product from ethanol to yield 71.1% powder meeting British Pharmacopeia 2007
standards. The products and all intermediates were fully characterized by
physical and spectroscopic methods. The overall yield was 20.01%, higher than
those reported (16-18%). In synthesis of finasteride, derivatives 3 and 4
showed optimal GOLD In silico docking
and inhibition of α-reductase.
KEYWORDS: Finasteride, benign
prostatic hyperplasia, androst-4-en-3,17-dione,
synthesis, Docking.