Totally Synthetic Steroid Hormones. XIII.¹ The Chemical Resolution of Some Racemic Estrane, 13β-Ethylgonane, and 13β-n-Propylgonane Derivatives and the Preparation of Some Estrane and 13β-Ethylgonane Derivatives of Unnatural Configuration

Abstract

SYKTHETIC STEIWID H o i t m m s . XI11 199 the extent of binding to protein of the four adenosine atianiant'oat'es have been initiated in our l a b o r a t o r i e~.~~ In conclusion, the nucleoside adamant'oates as well m the adamantane-cont'aining agents earlier described may derive their high efficacy, a t least in part, through : L process of precise and specific binding of the adamant m e moiety to complement'ary, lipoid regions of the protein receptor site molecule.Saturally, binding t o protein of adamant'ane-contaiiiing agents acting in vivo may also affect their absorption arid their distribution (transport) in the animal host. The effect' of protein binding on these processes may be responsible for the quantitat'ive differences seen between the in ciuo activities, on the one hand, of the monomethylated analogs relat'ive to the adamantane a,geiit in the sulfonylurea series7 (about 25y0) and the nortestosterone esters2 (about 15-20%), and on the (-18) Preliminary results indicate the possibility t h a t the effect of methyl 3ubatitution on partition values parallel the test results obtained in the platelet ayeregation studies (Table Xj. T h e help of Rlr. 11. 11. Marsh and aswciatps, .\naIytical Research and Development Division, T h e Lilly riesearcli Laboratories, in obtaining tliese results is gratefully acknowledged.other hand, the activity of adenosine moiiomethyladamantoate relative to the adamantoate (about 130%) in inhibiting platelet aggregation in viti3o (Table The study of a different class of adamantane-containing agents which display a structure-activity relationship opposite to that reported in this paper and which presumably do not benefit from binding to protein will be the subject of a forthcoming publication.Acknowledgments.-The authors are grateful to 11r. W. L. Brown and asqociates for microanalyses; to

Enantiomeric Steroids: Synthesis, Physical, and Biological Properties

“…ent-Estradiol 135 showed activity comparable to that of estradiol in antilipemic tests in rats without feminizing activity. 70 ent-Estradiol methyl ether is more selective in the inhibition of rat liver micorsomal P-450 than estradiol methyl ether. 71 Clearly, these are areas for further research on ent-steroids.…”

A facile total synthesis of ent-17β-estradiol and structurally related analogues

“…The combined extracts were washed with brine and dried. Solvent removal, chromatography (20% EtOAc in hexanes) and recrystallization from acetone/hexanes gave product 17a (30 70 (s, 3H, C 18 -CH 3 ), 2.77-2.78 (m, 2H, C 6 -CH 2 ), 3.75 (q, J = 6 Hz, 1H, C 17 -H), 6.54 (d, 1H, J = 2.4 Hz, C 4 -H), 6.59 (dd, 1H, J = 8.4 Hz, 2.4 Hz, C 2 -H), 7.10 (d, 1H, J = 8.4 Hz, C 1 -H); 13 24. (8α,13α,14β,17β)-Estra-1,3,5(10),9(11)-tetraene-3,17-diol (17b)-A solution of compound 16b (60 mg, 0.21 mmol) in anhydrous toluene (3 ml) under N 2 was added to DIBALH (1.5 M in toluene, 1.5 ml, 2.25 mmol).…”

Designing Total Syntheses

“…For example, after 149 and 150 were separated by fractional crystallization of their hemisuccinates, 149 was resolved as the Z-menthoxyacetate and 150 as the brucine salt of the hemisuccinate [53]. Conversion to the hemisuccinate permitted resolution of 151 with dehydroabietylamine or with ephedrine [121]. The 3-methyl ether of estradiol was resolved via ester formation at C-17 with ( + )-diacetyltartaric acid methyl ester [121,122].…”

“…Conversion to the hemisuccinate permitted resolution of 151 with dehydroabietylamine or with ephedrine [121]. The 3-methyl ether of estradiol was resolved via ester formation at C-17 with ( + )-diacetyltartaric acid methyl ester [121,122]. 5-Hydroxy-10-methyl-A 1(9) -2-octalone (dihydro-119, Scheme 1-11), and the 10-ethyl and 10-isopropyl homologs, were converted to their corresponding phthalate half esters and resolved by means of their brucine salts [123].…”