Estrone - API Active Pharmaceutical Ingredient

Estrone

Name	Estrone
Synonyms	1,3,5(10)-ESTRATRIEN-3-OL-17-ONE 1,3,5[10]-ESTRATRIENE-3-OL-17-ONE 1,3,5-ESTRATRIEN-3-OL-17-ONE 3beta-hydroxyestra-1,3,5(10)-trien-17-one 3-HYDROXY-1,3,5[10]-ESTRATRIEN-17-ONE 3-HYDROXY-ESTRA-1,3,5(10)-TRIEN-17-ONE beta-estrone DELTA1,3,5(10)-ESTRATRIEN-3-OL-17-ONE DESTRONE E 1 ESTROL ESTRONE FOLLICULIN KESTRONE OESTRIN OESTRONE OESTRONE (E1) (8R,13S)-3-Hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one 1,3,5(10)-Oestratrien-3-ol-17-one 1,3,5-Oestratrien-3-ol-17-one
CAS NO	53-16-7
EINECS	200-164-5
Molecular Weight	270.37
Molecular Formula	C18H22O2
Melting point	258-260 °C(lit.)
Alpha	158 º (c=1, dioxane)
Boiling point	353.48°C (rough estimate)
Density	1.2360
Refractive index	165 ° (C=1, Dioxane)
Flash point	9℃
Storage temp	Refrigerator
Pka	pKa 10.77±0.02(H2O)(Approximate)
Form	Crystalline Powder or Crystals
Color	White to almost white
Water Solubility	0.03 g/L
Merck	3708
BRN	1915077

Safety Information
Hazard Codes	T,F
Risk Statements	45-60-61-64-40-63-39/23/24/25-23/24/25-11
Safety Statements	53-45-36/37-16
RIDADR	UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany	3
RTECS	KG8575000
Hazardous Substances Data	53-16-7(Hazardous Substances Data)
HS Code	29335995

1,3,5(10)-Estratrien-3-ol-17-one Usage And Synthesis
Chemical Properties	Crystalline Solid
Chemical Properties	Estrone is an odorless white crystalline powder.
Originator	Estrone,Abbott
Uses	Estrone is a metabolite of 17β-Estradiol (E888000). During the metabolism, it is in rapid equilibrium with Estriol (E888960) and 17β-Estradiol (E888000) (1). Causes the feminization of male fish at human and animal waste sites (2). This compound is a contaminant of emerging concern (CECs). Drinking water contaminant candidate list 3 (CCL 3) compound as per United States Environmental Protection Agency (EPA), environmental, and food contaminants.
Uses	A metabolite of 17β-Estradiol.
Uses	estrogen
Definition	ChEBI: A 17-oxo steroid that is estra-1,3,5(10)-triene substituted by an hydroxy group at position 3 and an oxo group at position 17.
Manufacturing Process	1-Vinyl-1,2,3,4-tetrahydronaphthalene-1,6-diol reacts with 2- methylcyclopentane-1,3-dione in the presence of Triton B in tert-butanol gives a good yield of δ1,3,5(10),9(11)-8,14-secoestratetraen-3-ol-14,17-dione, melting point 124°-126°C (from methanol). δ1,3,5(10),9(11)-8,14-Secoestratetraen-3-ol-14,17-dione under influence of hydrochloric acid in tetrahydrofurane cyclises into δ1,3,5(10),8,14-estrapentaen- 3-ol-17-one, melting point 216°-218°C. δ1,3,5(10),8,14-Estrapentaen-3-ol-17-one is converted to d,l-8-dehydroestrone by selective hydrogenation with hydrogen, melting point 251°-254°C (from methanol). Exhaustive hydrogenation of δ1,3,5(10),8,14-estrapentaen-3-ol-17- one give d,l-8-isoestrone. d,l-8-Isoestrone in the presence of hydrochloric acid in tetrahydrofurane isomerizes into d,l-9(11)-dehydroestrone, melting point 262°-265°C (from alcohol). Hydrogenation of d,l-9(11)-dehydroestrone in tetrahydrofuran in the presence of Pd/CaCO3 yields the estrone, melting point 251°-252°C (from acetone).
Brand name	Estrogenic Substance (Wyeth); Theelin (Parkdale)
Therapeutic Function	Estrogen
General Description	Estrone, 3-hydroxyestra-1,3,5(10)-trien-17-one, is less active than estradiol but more active than itsmetabolite, estriol. As the salt of its 3-sulfate ester, estroneis the primary ingredient in conjugated estrogens, USP, andesterified estrogens, USP. Although originally obtainedfrom the urine of pregnant mares (about 10 mg/L), estroneis now prepared synthetically. Estrone itself is not availablein commercial oral formulations, but can be obtained at compounding pharmacies as a topical formulation. Oleoylestrone,the C3 ester of estrone with oleic acid, is in phase IIclinical trials for the treatment of obesity. This acyl estronederivative reduces fat stores by a mechanism not involvingthe ER, although some of the oleoyl-estrone is hydrolyzedto estrone in vivo.
Hazard	A carcinogen (OSHA)
Safety Profile	Confirmed carcinogen with experimental carcinogenic, neoplastigenic, tumorigenic, and teratogenic data. A poison by intraperitoneal and subcutaneous routes. Human reproductive effects by implantation: spermatogenesis and impotence. Mutation data reported. A steroid drug for the treatment of menopause and ovariectomy symptoms. When heated to decomposition it emits acrid smoke and irritating fumes.
Potential Exposure	Synthesized from ergosterol. Used in combination with progestogen as an oral contraceptive.
Shipping	UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials.
Purification Methods	Purify estrone by chromatography on silica gel, eluting with 2:1 hexane/EtOAc and recrystallising from EtOH or Et2O/EtOH. [Danishefsky & Cain J Am Chem Soc 98 4975 1976.] The acetate [901-93-9] crystallises from EtOH with m 125-127o. [Beilstein 8 III 1171.]
Incompatibilities	May react exothermically with reducing agents to generate flammable gaseous hydrogen. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, and epoxides.

1,3,5(10)-Estratrien-3-ol-17-one Preparation Products And Raw materials
Raw materials	Isopropyl acetate-->Acetylacetone-->CHLORIC ACID-->2,4,6-Collidine-->5-ALPHA-ANDROSTANE-->Hydrogen-->Hydrochloric acid-->Palladium-->Bis(4-hydroxyphenyl) Sulfone-->Benzyltrimethylammonium hydroxide-->19-DIOL 3-ACETATE
Preparation Products	Oxendolone-->β-ESTRADIOL-->16,17-Epoxy-3,17-dihydroxyestra-1,3,5(10)-triene-3,17-diacetate-->Ethynyl estradiol-->estra-1,3,5(10),16-tetraene-3,17-diol diacetate-->Estriol

1,3,5(10)-Estratrien-3-ol-17-one Preparation Products And Raw materials

Raw materials

Isopropyl acetate-->Acetylacetone-->CHLORIC ACID-->2,4,6-Collidine-->5-ALPHA-ANDROSTANE-->Hydrogen-->Hydrochloric acid-->Palladium-->Bis(4-hydroxyphenyl) Sulfone-->Benzyltrimethylammonium hydroxide-->19-DIOL 3-ACETATE

Preparation Products

Oxendolone-->β-ESTRADIOL-->16,17-Epoxy-3,17-dihydroxyestra-1,3,5(10)-triene-3,17-diacetate-->Ethynyl estradiol-->estra-1,3,5(10),16-tetraene-3,17-diol diacetate-->Estriol