968-93-4

Basic information

• Product Name: Testolactone
• Synonyms: TESTOLACTONE;1,2,3,4,4a,4b,7,9,10,10a-decahydro-2-hydroxy-2,4b-dimethyl-7-oxo-1-phenanthren;1,2-dehydrotestololactone;1,2-didehydro-testololacton;17alpha-oxo-d-homo-1,4-androstadiene-3,17-dione;17-secoandrosta-1,4-dien-17-oicacid,13-hydroxy-3-oxo-1delta-lactone;1-dehydrotestololactone;delta(1)-dehydrotestolactone
• CAS NO: 968-93-4
• Molecular Formula: C₁₉H₂₄O₃
• Molecular Weight: 300.39
• EINECS: 213-534-6
• Product Categories: Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 968-93-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 218-219°
• Boiling Point: 482 °C at 760 mmHg
• Flash Point: 213.4 °C
• Appearance: /
• Density: 1.17 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.567
• CAS DataBase Reference: Testolactone(CAS DataBase Reference)
• NIST Chemistry Reference: Testolactone(968-93-4)
• EPA Substance Registry System: Testolactone(968-93-4)

Safety Data

• Hazardous Substances Data: 968-93-4(Hazardous Substances Data)

Usage

Originator

Fludestrin,Heyden,W. Germany,1968

Uses

Different sources of media describe the Uses of 968-93-4 differently. You can refer to the following data:
1. Antineoplastic; non-selective steroidal aromatase inhibitor that prevents the conversion from androgen to estrogen. Used in in the treatment of familial male precocious puberty. An effective anti-tumor agent.
2. Testolactone USP (Teslac) is used to treat Breast cancer.

Manufacturing Process

(a) Fermentation: A medium of the following composition is prepared: 3.0 grams cornsteep liquor solids; 3.0 grams NH4H2PO4; 2.5 grams CaCO3; 2.2 grams soybean oil; 0.5 gram progesterone and distilled water to make 1 liter. The medium is adjusted to pH 7.00.1. Then, 100 ml portions of the medium are distributed in 500 ml Erlenmeyer flasks and the flasks plugged with cotton and sterilized in the usual manner (i.e., by autoclaving for 30 minutes at 120°C). When cool, each of the flasks is inoculated with 5 to 10% of a vegetative inoculum of Cylindrocarpon radicola [the vegetative inoculum being grown from stock cultures (lyophilized vial or agar slant) for 48 to 72 hours in a medium of the following composition: 15 grams cornsteep liquor; 10 grams brown sugar; 6 grams NaNO3; 0.001 gram ZnSO4; 1.5 grams KH2PO4;0.5 gram MgSO47H2O; 5 grams CaCO3; 2 grams lard oil; and distilled water to make 1 liter].The flasks are then placed on a reciprocating shaker (120 one and one-half inch cycles per minute) and mechanically shaken at 25°C for 3 days. The contents of the flasks are then pooled and, after the pH of the culture is adjusted to about 40.2 with sulfuric acid, filtered through Seitz filter pads to separate the mycelium from the fermented medium.(b) Extraction: 40 liters of the culture filtrate obtained in (a) is extracted with 40 liters chloroform in an extractor (e.g., Podbelniak, US Patent 2,530,886, or improvements thereon) and the filtered chloroform extract is evaporated to dryness in vacuo. The residue (11.1 grams) is taken up in 200 ml of 80% aqueous methanol, and the resulting solution is extracted four times with 100 ml portions of hexane. The 80% aqueous methanol solution is then concentrated in vacuo until crystals appear; and, after cooling at 0°C for several (usually about 3 to 4) hours, the crystals formed are recovered by filtration. About 2.9 grams 1-dehydrotestololactone (MP 217° to 217.5°C) are thus obtained. Concentration of the mother liquors yields additionally about 6.0 grams of the lactone. Recrystallization from acetone yields a purified 1-dehydrotestololactone having a melting point of 218° to 219°C.

General Description

Testolactone, 13-hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acidΔ-lactone (Teslac),was originally synthesized as a possible anabolic steroid,considering its structural similarity to testosterone. The keystructural difference from anabolic steroids is the D-ring lactone instead of the typical cyclopentyl ring. Althoughconsidered in many texts an androgen or anabolic steroid (itis a Schedule III drug because of its classification as an anabolicsteroid), testolactone lacks androgenic effects in vivo.Its action is believed to be caused by irreversible inhibitionof aromatase. It is a relatively weak inhibitor of aromatase,but the irreversible nature of the inhibition can lead to prolongedeffects. Its relatively weak inhibition of aromataseand its undesirable dosage schedule (5×50-mg tabletsq.i.d.) give this older agent only limited use in breast cancertreatment because of better available options.

InChI:InChI=1/C19H24O3/c1-18-9-7-13(20)11-12(18)3-4-14-15(18)8-10-19(2)16(14)5-6-17(21)22-19/h7,9,11,14-16H,3-6,8,10H2,1-2H3/t14?,15-,16-,18?,19?/m0/s1

Upstream product

• 58-22-0 testosterone 
• 57-83-0 Progesterone 
• 145-13-1 Pregnenolone 
• 63-05-8 Androstenedione 
• 897-06-3 androsta-1,4-diene-3,17-dione 
• 64-85-7 21-Hydroxyprogesterone 
• 152-58-9 Cortexolone 
• 1236-09-5 pregn-5-ene-3,20-dione 
• 846-48-0 1-dehydrotestosterone 
• 897-06-3 Androsta-1,4-diene-3,17-dione 
• 53-43-0 dehydroepiandrosterone 

Downstream Products

• 6947-44-0 1α,5-disulfanediyl-17a-oxa-D-homo-5α-androstane-3,17-dione 

Relevant articles and documents

Effective multi-step functional biotransformations of steroids by a newly isolated Fusarium oxysporum SC1301

A fungus Fusarium oxysporum SC1301 was isolated from soil samples, which could transform androst-4-ene-3,17-dione, androst-1,4-diene-3,17-dione, dehydroepiandrosterone, progesterone, testosterone, and pregnenolone to give testolactone in 76-98% yields. Especially, for progesterone and pregnenolone, multi-step functional transformations, including oxygenative esterification of 20-ketosteroids, hydrolysis of ester, oxidation of C-17 OH group, oxygenative lactonization of 17-ketosteroids, 1-dehydrogenation, oxidation of C-3 OH group and Δ5→4 CC bond migration, could proceed effectively to yield testolactone as a single product. This is the first example that a F. oxysporum species shows catalytic capability of ring-D lactonization. The results are remarkably distinguished from those previously reported for the closely-related fungus F. oxysporum var. cubense, which predominantly mediates the hydroxylations at different positions of steroids. In addition, F. oxysporum SC1301 may serve as a valuable biocatalyst for the production of testolactone.

Steroids' transformations in Penicillium notatum culture

The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15α-hydroxylation of 17α-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield.

Microbiological oxidation of progesterone by Fusarium Solani.

-