STEROIDS AND RELATED PRODUCTS: XVII. THE SYNTHESIS OF 3,9,12,20-TETRAOXYGENATED 9,12-seco-STEROIDS. PART II

Abstract

I t is shown that the ozonolysis of A"c1)-12-l<eto steroids with a trans fusion of rings A and B proceeds in better yields than the corresponding opening of ring C in the sterically more hindered A/B-cis series. The syntheses of 23~-bromo-3~-11ydroxy-9-oso-9,12-seco-25-iso-5a,22p-spirostan-12-oic acid and some of its derivatives as well as of 3P,20a-dihydrox)~-9-oxo-9,12-seco-12-pregnanoic acid and some of its ester derivatives are reported. I t is de~nonstrated that the reduction with l i t h i~~~n a l u m i n~~n~ hydride in tetrahydrofuran of a 12,30-diketone leads to a 12p,2On-dihydrosy derivative, in contradistinction to the reduction of a 12~-acetosy-20-l~etone, 1%-hich affords mostly the 208-alcohol.I n Part I of this study ( I ) , we described an opening of ring C of the steroid nucleus, in the presence of protected alcohol functions in positions 3 a i d 20, leading to a 9-0x0-9,12-seco-12-acid derivative of type 11. The fission of ring C was effected by ozonolysis of a A"11'-12-ketone (compare I), a reaction which gave o~ily a low yield of the desired seco product.An inspection of models (compare Fig. 1) suggests that this reaction should proceed in better yields in the case of steroids with a t r a m fusioil of rings A and B. I t can be 'Part of the results reported i?t this paper. were the sz~bject of a conimzlnzcatzon presented before tlte

The Conformation of 20-Oxopregnane Hormone from Molecular Orbital Calculations and a Consideration of the Cortisol Receptor

“…We therefore considered only the cyclopentane 1) ring of the three molecules studied with three variations at C-17, namely, as in I la for progesterone, in lit) for corticosterone, and in lie for cortisol. These simplifications are justifiable from the basic nature of conformational preference.16 17 The theoretical basis for the validity of our neglect of distant atoms is found in the appendix.…”

The Purification of Solvents for Ultraviolet Absorption Spectroscopy

“…distillatioil o r passage t h r o u g h a c o l u m n of s u i t a b l e a d s o r b e n t s u c h as alulllilla o r silica gel (1)(2)(3)(4). In t h e c o u r s e of the purification of a l a r g e n u m b e r of h y d r o c a r b o n s r a n g i n g from p e n t a n e to tetradecane a n d c y c l o p e n t a n e to c y c l o o c t a n e , for u s e i n 5 to 10 cm thicltnesses in t h e 2500-2600 A r e g i o n , t h e following p r o c e d u r e was f o u n d to be not o n l y t h o r o u g h b u t also quiclc a n d c o n v e n i e n t .…”

Aza Steroids: Iii. Synthesis of 11-Aza Steroids—a Novel Class of Steroidal Sapogenin Analogues

“…I t was therefore necessary t o prepare the appropriate 9,12-seco steroidal intermediates which, in turn, could be cyclized in the presence of an amine t o provide the 11-aza steroid. The most direct approach to the desired 9,12-seco steroids involved ozonolysis of a 9,ll-unsaturated 12-keto steroid since this type of reaction had been successfully employed by the present authors (1,2) and by Jacobs and Brownfield (5) in the synthesis of ring B seco derivatives and by Engel and co-workers (4,6,13) in the synthesis of sorne9,12-seco steroids. An attractive starting material for the ring-opening reaction was 9,11-dehydrohecogenin acetate, whieh was readily available from hecogenin acetate (7).…”

“…In addition t o the improved yield, it was also more convenient t o utilize this reagent in large-scale preparations of I and we have used this procedure in all our subsequent preparations. After this phase of the work was completed, a detailed study of the ozonolysis of A9.11-12-keto steroids was reported by Engel (4,13).…”