Physical Properties of Conjugates by Seymour Bernstein, J ohn P. Dusza, and J oseph P. J oseph Lederle Laboratories A Division of American Cyanamid Company Pearl River, New York

Springer-Verlag • Berlin • BeideZberg • N~w York • 1968 Contents

Acknowledgment v lntroduction and Scope lX

Catalog of Conjugates 1 A. Empirical formula index of parent 3 B. Catalog 12

References 199 A. Empirical formula index of parent steroids

3-Hydroxyestra-1 ,3,5(10) ,6,8-pentaen-17 -one (Equilenin) ...... 12

Estra-1,3 ,5(10) ,6,8-pentaene-3 ,17ß-diol (Dihydroequilenin) ...... 13 3-Hydroxyestra-1 ,3 ,5(10) ,7-tetraen-17 -one (E quilin) ...... 14

Estra-1,3,5(10) ,6-tetraene-3 ,17ß-diol (6-Dehydro-17ß-) ...... 15 Estra-1,3 ,5(10), 7-tetraene-3 ,17ß-diol (Dihydroequilin) ...... 16 3-Hydroxyestra-1 ,3 ,5(10)-trien-17 -one () ...... •...... ,.· .. ~ • . . 17

2,3-Dihydroxyestra-1,3 ,5(10)-trien-17-one (2-Hydroxyestrone) ...... 20 3 ,16a-Dihydroxyestra-1,3 ,5 ,(10)-trien-17 -one (16a-Hydroxyestrone) ...... r • • • • • • • 21 3 ,16ß-Dihydroxyestra-1 ,3,5(10)-trien-17-one (16ß-Hydroxyestrone) . . • . . . . • ...... 23 3 ,17ß-Dihydroxyestra-1,3,5(10)-trien-16-one (16-Keto-17ß-estradiol) ...... 24

Estra-1,3,5(10)-trien-3-ol ...... •... 25

Estra-1,3 ,5(10)-triene-3 ,17a-diol (17a-Estradiol). . . • • ...... 26 Estra-1,3,5(10)-triene-3 ,17ß-diol (17 ß-Estradiol, estradiol) • . . . . . • . . • . . 27 f':"c

3 4 c1aH24o3 Estra-1 ,3 ,5(10)-triene-2,3 ,17ß-triol (2-Hydroxy-17ß-estradiol, 2-hydroxyestradiol) .•...... 33 Estra-1 ,3 ,5(1 0)-triene-3 ,15a,l7ß-triol (15a-Hydroxy-17ß-estradiol, 15a-hydroxy- estradiol) ...... •.. 34 Estra-1,3 ,5(10)-triene-3 ,16a,17a-triol (17 -) ...... 35 Estra-1,3 ,5(10)-triene-3 ,16a,l7ß-triol () ...... 36 Estra-1 ,3 ,5(10)-triene-3 ,16ß,l7ß-triol (16-Epiestriol)...... 44 claHzaOz 17ß-Hydroxyestra-4-en-3-one (19-Nortestosterone)...... 46 cl9H24o3 Androst-4-ene-3 ,11,17-trione () .....•.....••..... 47

ClgHzaÜz Androst-4-ene-3 ,17-dione ()...... •....• 48 17ß-Hydroxyandrosta-4,9(11)-dien"-3-one (9-Dehydrotestosterone) ...... 49

~gHza03 llß-Hydroxyandrost-4-ene-3 ,17 -dione ..•... 50 17ß-Hydroxyandrost-4-ene-3,11-dione (11-Ketotestosterone) ...••...•....• 51 3ß-Hydroxyandrost-5-ene-7,17-dione (7-Ketodehydroisoandrosterone, 7-keto­ ) ...... 52

5a-Androstane-3,17 -dione (Androstanedione). . • • . . • . • • . . . . • . • 53 5ß-Androstane-3 ,17-dione (Etiocholanedione) ...... • • . . • . . . . 54 17a-Hydroxyandrost-4-en-3-one () • • • . . . . • . . . . • . . . . 55 17ß-Hydroxyandrost-4-en::3-one () ...•. : . . . . • ...... 56 ~ 'II" 5

3ß-Hydroxyandrost-5-en-17-one {Dehydroisoandrosterone,dehydroepiandro- sterone, androstenolone) ...... 59

3a-Hydroxy-5a-androstane-11,17 -dione (11-Ketoandrosterone) ...... 63 3a-Hydroxy-5ß-androstane-11 ,17-dione (11-Ketoetiocholanolone) ...... 64 6ß,l7ß-Dihydroxyandrost-4-en-3-one (6ß-Hydroxytestosterone) ...... 65 lla,l7ß-Dihydroxyandrost-4-en-3-one {11a-Hydroxytestosterone) ...... 66 llß,l7ß-Dihydroxyandrost-4-en-3-one {11ß-Hydroxytestosterone) ...... 67 14a,l7ß-Dihydroxyandrost-4-en-3-one (14a-Hydroxytestosterone) ...... • 68 3ß,7a-Dihydroxyandrost-5-en-17-one {7a-Hydroxydehydroisoandrosterone, 7 a-hydroxydehydroepiandrosterone). . . . . 69 3ß,l6a-Dihydroxyandrost-5-en-17-one {16 a-Hydroxydehydroisoandrosterone,'" 16a-hydroxydehydroepiandrosterone) .... 70

5a-Androst-16-en-3a-ol...... • 71

Androst-5-ene-3ß,l7a-diol ...... ••. 72 Androst-5-ene-3ß,l7ß-diol

{) •...... 1 • • • • • • • • • • 73 3a-Hydroxy-5a-androstan-17-one {) . • ...... • . . • • . . • 75 3ß-Hydroxy-5a-androstan-17-one (Isoandrosterone, ) •.... 78 3a-Hydroxy-5ß-androstan-17-one () . • • ...... • . • • . . . . 80 3ß-Hydroxy-5ß-androstan-17-one ...... •.• 82

17ß-Hydroxy-5a-androstan-3-on~ ...... •. 83 6

Androst-5-ene-3ß,16a,17ß-triol (Androstenetriol)...... • ...... • 84 Androst-5-ene-3ß,16ß,17a-triol...... 85 3a-Hydroxy-17a-oxa-D-horno-5ß-androstan- 17-one ...... • . . . . • . 86 3a,llß-Dihydroxy-5a-androstan-17-one (llß-Hydroxyandrosterone) ...... • 87 3a,11ß-Dihydroxy-5ß-androstan-17-one (llß-Hydroxyetiocholanolone)...... 88

5a-Androstane-3a,17a-diol 89 5a-Androstane-3a,17ß-diol 90 5a-Androstane-3ß, 17 ß-diol 91 5ß-Androstane-3a,17ß-diol 92 5ß-Androstane-3ß,17ß-diol 93

5a-Androstane-3a,16ß,17a-triol . • . . • . . . . . 94

17a-Ethynylestra-1 ,3 ,5(10)-triene-3 ,17ß-diol ( Ethynylestradiol) ...... • . • . . 95

17ß-Carboxyandrost-4-en-3-one (3-Keto-4-etienic acid)...... • . . . • • • 96 17a-Hydroxy-19-norpregn-4-ene-3,20-dione.. 97

17 ß-Hydroxy -17 a-rnethylandrost-4-en-3 -one (Methy ltestosterone)...... • ...... 98

17a-Methylandrost-5-ene-3ß,17ß-diol (Methylandrostenediol) . . • • • . • . . • • • . 99

C21H260 3 17a-Hydroxypregna-1,4,6-triene-3,20-dione .. 100

C21H260 5 17a,21-Dihydroxypregna-1,4-diene-3 ,11,20-trione (Prednisone) ...... 101

C21H27F06 9a-Fluoro-llß,16a,17a,21-tetrahydroxypregna-1,4- diene-3,20-dione (Triarncinolone) ....r~ • • • • • • • • • • • • • 102 7

21-Hydroxypregn-4-ene-3, 11 ,20-trione (Dehydrocorticosterone) ...... 103

11ß,21-Dihydroxy-3,20-dioxopregn-4-en-18-al () ...... 104 17a,21-Dihydroxypregn-4-ene-3 ,11 ,20-trione ()...... 105 11ß ,17a,21-Trihydroxypregna-1 ,4-diene-3 ,20-dione (Prednisolone)...... 107

C21Hza0a 11ß,16a,17a,21-Tetrahydroxypregna-1 ,4-diene- 3,20-dione (16a-Hydroxyprednisolone) ...... 109

C21H2gF05 9a-Fluoro-11ß,17o,21-trihydroxypregn-4-ene- 3 ,20-dione (9a-Fluorohydrocortisone, 9a-fluorocortisol).. 110

CzlH3ooz 3ß-Hydroxypregna-5 ,16-dien-20-one ...... 111 Pregn-4-ene-3 ,20-dione () ...... 112

CzlH3oo3 6ß-Hydroxypregn-4-ene-3,20-dione (6ß-Hydroxyprogesterone) ...... 113 17a-Hydroxypregn-4-ene-3,20-dione (17a-Hydroxyprogesterone) ...... 114 21-Hydroxypregn-4-ene-3,20-dione (Deoxycorticosterone, cortexone) ...... 115 c21H3oo4 11ß,21-Dihydroxypregn-4-ene-3,20-dione () ...... 116 17a,21-Dihydroxypregn-4-ene-3 ,20-dione (Compound S) ...... 117

CzlH3oos 6ß,11ß,21-Trihydroxypregn-4-ene-3,20-dione (6ß-Hydroxycorticosterone) .•...... • 119 llß ,17a,21-Trihydroxypregn-4-ene-3 ,20-dione (Hydrocortisone, ) .. ; •...... 120

), -II"1 .•• :~ ~ 8

6ß ,llß ,17a,21-Tetrahydroxypregn-4-ene-3 ,20-dione ( 6ß-Hydroxyhydrocortisone, 6ß-hydroxycortisol) •...... 122 c21H32o2 3ß-Hydroxypregn-5-en-20-one () ...... 123 3ß-Hydroxy-5a-pregn-16-en-20-one ...... 125

C21H3203 3a-Hydroxy-5ß-pregnane-11,20-dione ...... 126 3ß,17a-Dihydroxypregn-5-en-20-one (17 a-Hydroxypregnenolone) .....•.•.. 127 3ß,21-Dihydroxypregn-5-en-20-one ...... 129 c21H3204 3a ,21-Dihydroxy-5a-pregnane-11 ,20-dione ... 130 3a,21-Dihydroxy-5ß-pregnane-11 ,20-dione ... 131 3ß ,17 a,21-Trihydroxypregn-5-en-20-one .... 132

3a,11ß,21-Trihydroxy-20-oxo-5ß-pregnan-18-al (Tetrahydroaldosterone) ..•..•...... 133 3a,17a,21-Trihydroxy-5ß-pregnane-11 ,20-dione (Tetrahydro-E, tetrahydrocor.tisone). . • . 134

3a-Hydroxy-5a-pregnan-20-one . . . . . • • • • • 135 3ß-Hydroxy-5a-pregnan-20-one . . . . • • • . . . 136 3a-Hydroxy-5ß-pregnan-20-one () . • ...... • ...... 138 3ß-Hydroxy-5ß-pregnan-,20-one ...... • 140 Pregn-5-ene-3ß,20a-diol 141 Pregn-5-ene-3ß,20ß-diol ...... 143

3a,17a-Dihydroxy-5ß-pregnan-20-one ...... 144 3a,21-Dihydroxy-5ß-pregnan-20-one...... 145 Pregn-5-ene-3ß,l7a,20a-triol .•.....•.•• 146

3a,llß,21-Trihydroxy-5a-pregnan-20-one • . . 147 3a,llß,21-Trihydroxy-5ß!"pregnan-20-one () • ...... • . . 148 ~ !,, 9

3ß,llß,21-Trihydroxy-5a-pregnan-20-one . . • 149 3a,17a,21-Trihydroxy-5ß-pregnan-20-one (Tetrahydro-S) ...... • 150 3ß,17o,21-Trihydroxy-5o-pregnan-20-one ... 151

3a,11ß,17a,21-Tetrahydroxy-5ß-pregnan-20-one (Tetrahydro-F, tetrahydrohydrocortisone,

)... 0 • • • • • • • • • • • • 152 3a,17 a,20a,21-Tetrahydroxy-5ß-pregnan-11-one (Cortolone)...... 154 3a,17a, 20ß,21-Tetrahydroxy-5ß-pregnan-11-one (ß-Cortolone) ...... 155

5a-Pregnane-3a,20a-diol ...... 156 5 a-Pregnane-3ß,20ß-diol ...... 157 5ß-Pregnane-3 a,20a-diol ()...... 158 5ß-Pregnane-3a,20ß-diol ...... •... 160

5 a-Pregnane-3ß,17a,20ß-triol •...... 161 ,",,,._ 5ß-Pregnane-3a,17o,20~ triol ...... 162

5a-Pregnane-3ß,20~,21-triol ....•...... 163

5ß-Pregnane-3a,llß ,17 a,20a,21-pentol ( Cortol) ....•.•...... ••.• , . . . . 164 5ß-Pregnane-3a,11ß,17 a,20ß,21-pentol (ß-Cortol) . o •••••••••• , • • • • • • • • 165

C21H37NO 20a-Amino-5a-pregnan-3ß-ol ...... 166

C22H280 3 17a-Hydroxy-1a,2a-methanopregna-4,6-diene- 3,20-dione ...... •...... •...... 167

9a-Fluoro-11ß ,17a,21-trihydroxy-16a-methyl­ pregna-1,4-diene-3,20-dione (Dexamethasone). ....•••.••••...• 168

9a-Fluoro-11ß,17a,21-trihydroxy-~.6ß-methyl- pregna-1,4-diene-3,20-dione · (Betamethasone) ..•..•... 169 10

17a-Hydroxy-6a-methylpregn-4-ene- 3 ,20-dione ...... 170

11ß ,17 a,21-Trihydroxy-16a-methylpregn-4-ene- 3 ,20-dione ...... •.... 171

3ß-Hydroxy-17a-methylpregn-5-en-20-one .. 172

3ß,17a-Dihydroxy-6-methylpregn-5-en- 20-one ...... 173

3ß,14ß,Dihydroxy-5ß-card-20(22)-enolide (Digitoxigenin) ...... 174

Cholest-4-en-3-one (Cholestenone) ...... • . 175 Cholesta-5, 7 -dien-3ß-ol (7 -Dehydrocholesterol) . . . . . • ...... 176

Vitamin D3 • • • • • • • • • • • • • • • • • • • • • • • 177

Cholest-5-en-3a-ol (Epicholesterol) . . • ...... 178 Cholest-5-en-3ß-ol ( ) ...... • ...... 179

Cholest-5-ene-3ß,20a-diol (20a-Hydroxycholesterol) ...... 182

5a-Cholestan-3a-ol. • . . . . . • . • ...... 183 5a-Cholestan-3ß-ol (Cholestanol) ...... 184

5a-Cholestan-3ß, 7a-diol...... • . . • . . . 185 5a-Cholestane-3ß,7ß-diol ...... •••. 186

Cholestane-3ß,5a,6ß-triol. 0 •••••••••••• 187

5a-Cholestane-3ß, 7 a,16a,26-tetrol (Myxinol). . . . • • • . . . . • • . . . • . . . . • 188 11

Ergosta-5,7 ,22-trien-3ß-ol (Ergosterol) ...... • ...... 189

Vitamin D2 • • • • • • • • • • • • • • • • • • • • • • • • 190

Stigtnasta-5 ,22-dien-3ß-ol (Stigmasterol)...... • ...... 191

Stigmast-5-en~3ß-ol (ß-Sitosterol) ...... 192

5a-Stigmastan-3ß-ol • • • . . • . • . . . . • . . • • 194

Lanosta-7 ,9(11)-dien-3ß-ol • • • • • • • . • . . . • 195 Lanosta-8 ,24-dien-3ß-ol (Lanosterol) ...... • ...... 196

Lanost-8-en-3ß-ol. . • ...... • • . . • . • . . 197

Fusidic acid . . . • . . • . . . . • • • • . . . . . • . . 198

' ·-~ ',..