Development of Steroid Chemistry in Pakistan Because of Its Pharaceutial as Well as Socio-Economic Impact

Abstract

Pakistan is importing a large number of expensive steroidal life-saving drugs and steroidal hormones at an estimated cost of Rs. 50 million per annum. These drugs and hormones such as cortisone, hydrocortisone, dexamethasone, prednisolone, progesterone, testosterone, methyl testosterone, and contraceptive steroids are mainly produced from diosgenin, hecogenin and tigonenin which are naturally occurring steroidal sapogenins of vegetable origin. The promising plant source in Pakistan are Dioscorea and ticodenin etc. Dioscorea deltoides grows wild in the northern region of Pakistan, while fenugreek is cultivated in the plains. The present work describe the physico-chemical studies on the roots of Dioscorea deltoides and Fenugreek for diosgenin content and the production of diosgenin on a pilot plant scale. This work also describe chemical conversion of Diosgenin to 16-dehydro-pregnenolone Acetate (16-DPA) and dehydro apiandrosterone which important key steroidal intermediates. These key intermediates were also converted to progesterone and 17α-methyl-androst-5en-3β, 17β-idol. Preliminary laboratory studies showed that the old roots of Dioscorea deltoides from kaghan and Indus vallies contained about 4 to 8 percent of diosgenin on a dry basis. Optimum conditions were standardized for the recovery of diosgenin from the tubers on laboratory and pilot plant scale. Three pilot plant units such as slicing machine, hydrolysis vessel and solid -liquid solvent extractor were designed and fabricated for the extraction of diosgenin from the roots (Figures 1,2 & 3).

(II) Psycho-chemical studies of local Fenugreek (Metha-seeds) showed that the seeds contain 0.73 percent of a mixture of diosgenin and yamogenin, 6.4 percent of semi-drying oil and the residue meal containing 26 percent protein. The technical know-how has been developed for the production diosgenin from the roots of deltiodes and conversion of diosgenin to 16-dehy-deopregnenolone acetate. The local production these steroids will not only earn foreign exchange but also form a basis for more detailed studies for the production of steroidal drugs and intermediates. During the research and development work on the production of diosgenin and steroidal intermediates, we have given technical assistance to Kurram chemicals, Rawalpindi, by providing design of slicing machine, recommended the use of heptane instead of hexane and demonstrated the method for production of 16-hydropregnenolone acetate. We have also provided 1 kg each of pure diosgenin and 16-hydropregnenolone acetate as sample to Kurram Chemicals, to get evaluation of the products from the foreign pharmaceutical companies for marketing. During the research and development work on the production of steroidal intermediates, we have collected sufficient starting material and prepared 16-DPA. These can be utilized for more detailed studies for other steroidal intermediates and steroidal drugs.