Studies in the synthesis of cortisone. Part XII. Improvements in the conversion of sapogenins into pregnan-20-ones

Abstract

The conversion of steroidal sapogenins (I) into pregnan-20-ones (VI) by way of the 4-sapogenins (11) is improved, particularly for 1 l-oxotigogenin and its esters (Ic). In the first step furost-22-ens are evidently formed as well as the desired 4-sapogenins, but this difficulty and others are avoided by methods described.THE development of practicable means of making ll-oxotigogenin and its esters (Ic) from hecogenin (Ib; R = H) (Schmidlin and Wettstein, Helv. Chim. Acta, 1953Acta, , 36, 1241 Cornforth, Osbond, and Phillipps, J., 1954, 907) has prompted us to try to improve the published methods for converting 11-oxosapogenins into 3P-acetoxy-5a-pregnane-11 : 20dione (VIc; R = Ac), from which cortisone can be derived (Part VII,

A Simple Efficient Process for the Synthesis of 16-Dehydropregnenolone Acetate(16-Dpa)–A Key Steroid Drug Intermediate from Diosgenin

“…Gould et al [9] observed that the conversion could be achieved at the boiling point of acetic anhydride in the presence of acetyl chloride or anhydrous AlCl 3. Similar conditions using acetyl chloride also have been used for the transformation of ∆ 4,6 -22-isospirostadiene-3-one to the corresponding 3b-acetoxy-3,5,7-triene [11].…”

“…Afterwards several modifications have been made including catalytic conversion to effect this isomerization process [9][10][11][12][13]. Gould et al [9] observed that the conversion could be achieved at the boiling point of acetic anhydride in the presence of acetyl chloride or anhydrous AlCl 3.…”

“…Synthesis of 16-dehydropregnenolone acetate (16-DPA) 1 from solasodine 2 and diosgenin 3 has been reported by several workers in various literatures [4][5][6][7][8][9][10][11][12][13][14][15]. For the conversion of this spirostanic compound, diosgenin (22-iso-5-spirostane-3β-ol) into 16-DPA (3β-acetoxy-pregn-5,16-diene-20-one) 1, it must be isomerized first to furostenol derivative pseudodiosgenin diacetate (3β,26-diacetoxyfurosta-5,20(22)-diene) 4, through acetolysis (Figure 2), which on subsequent oxidation of the 20(22) enolic double bond followed by hydrolytic degradation furnishes 16-DPA [4][5][6][7][8][9][10][11][12][13][14][15].…”

“…are synthesized from 16-dehydropregnenolone acetate (16-DPA) 1, barring a few which are obtained by total synthesis. The plant origin compounds solasodine 2 and its oxygen analogue diosgenin 3 ( Figure 1) are the two main ingredients from which 16-DPA is generally synthesized [4][5][6][7][8][9][10][11][12][13][14][15]. Due to the favorable climatic condition of North East region of India, diosgenin yielding dioscorea species of plants, viz., D. compositae and D. floribunda grow abundantly in the region which led us to investigate commercial exploitation of these plants through large scale production of 16-DPA starting from diosgenin.…”

“…For the conversion of this spirostanic compound, diosgenin (22-iso-5-spirostane-3β-ol) into 16-DPA (3β-acetoxy-pregn-5,16-diene-20-one) 1, it must be isomerized first to furostenol derivative pseudodiosgenin diacetate (3β,26-diacetoxyfurosta-5,20(22)-diene) 4, through acetolysis (Figure 2), which on subsequent oxidation of the 20(22) enolic double bond followed by hydrolytic degradation furnishes 16-DPA [4][5][6][7][8][9][10][11][12][13][14][15]. Chemical transformations of spirostanic compounds also find importance towards the synthesis of plant growth promoting substances including ecdysteroids and some furostenols having significant phytotoxicity [18].…”