5a-Spirostan

The successful preparation of Il,ll-d2-5l5-androstan-3o -oh and 11,11-d2-(25R)-5a-spirostane in 83% and 91% isotopic purity by Raney nickel treatment of the 11,1 l-d2-12-ethylene thioketal derivatives further confirms the low degree of isotope scrambling with C-12 keto steroids. 

Homogeneous catalytic deuteration of various unsaturated 5a-spirostane derivatives is an excellent method for the preparation of side chain labeled analogs. Thus, saturation of the double bonds at positions 20(21), 23 and 24 provided the corresponding deuterated compounds (144), (145) and (146) in high isotopic purity. The preparation of (146) is a rare example of the saturation of an isolated trisubstituted double bond in the steroid field. 

Bromine can also be displaced with powdered zinc in ethanol-OD but this reaction is much slower and usually takes several days of heating under reflux. Nevertheless, this method is very useful in certain cases where neutral conditions are required as shown by the preparation of 23 -di-(25R)-5a-spirostan (222). Due to the sensitivity of the spirostan system to acid (see section II-F), removal of the 23-equatorial bromide in (221) was carried out with zinc in ethanol-OD yielding the deuterated product (222) in 93%... 

A mixture of lithium aluminum deuteride and aluminum chloride is a more powerful reducing agent than lithium aluminum deuteride itself. This is well illustrated by the opening of ring F in 5a-spirostan [(230) (231)] which otherwise is quite stable to lithium aluminum deuteride. The resulting 22-di-26-hydroxy-5a-furostan (231) exhibits better than 97% isotopic purity. 

Of the two competing pathways (44 -+ 45) and (44 -> 46) the one leading to C-23 deuteration (44-+45) is favored. Thus, when 5a-spirostan (44) is heated under reflux for 1 hour in acetic acid-OD or in ethanol-OD solution containing deuteriochloric acid, the 23,23-d2-analog (47, R = D) is obtained containing 90% of d2-species.78 Prolonged heating leads to the trideuterated... 

Agapanthussaponin D (= (25/ )-5a-Spirostane-2a,3(3,5a,9a-tetrol 3-0-Rha-[Gal]-Glc) (triterpene glycoside) Agapanthus inapertus (Liliaceae) [bulb, root] cAMP PDE (20)... 

Brisbagenin 1-0-Rha-acetylAra (= (257 )-5a-Spirostane-l(3,3(3-diol 1-0-Rha-acetylAra) (disaccharide steroidal saponin) Dichelostemma multiflorum (Liliaceae) [tuber] cAMP PDE (206)... 

Laxogenin 3-0-Glc-[Ara]-Glc (= (257 )-5a-Spirostan-3(3-ol-6-one 3-0-Glc-[Ara]-Glc) (trisaccharide steroidal saponin) Smilax sieboldii (Liliaceae) [rhizome] cAMP PDE (83)... 

Acetoxy-5a-spirostane series. Analysed by gas-liqnid chromatography (Ref. 113, unless otherwise indicated). <= "Digol = diethylene glycol [ HO(CH2)20(CH2)20H] "Diglyme = diethyleneglycol dimethyl ether [Me0(CH2)20(CH2)20Me], Ref. 1x2. 

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