16-Dehydropregnenolone acetate
Chemical compound
From Wikipedia, the free encyclopedia
16-Dehydropregnenolone acetate (16-DPA) is a chemical compound used as an intermediate or synthon in the production of many semisynthetic steroids. While it is not easy to synthesize, it is a convenient intermediate which can be made from other more available materials, and which can then be modified to produce the desired target compound.
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| Names | |
|---|---|
| IUPAC name
20-Oxopregna-5,16-dien-3β-yl acetate | |
| Systematic IUPAC name
(3aS,3bR,7S,9aR,9bS,11aS)-1-Acetyl-9a,11a-dimethyl-3a,3b,4,6,7,8,9,9a,9b,10,11,11a-dodecahydro-3H-cyclopenta[a]phenanthren-7-yl acetate | |
| Other names
16-DPA; 5,16-Pregnadien-3β-ol-20-one acetate; 3β-Hydroxy-5,16-pregnadien-20-one acetate; 3β-Acetoxy-5,16-pregnadien-20-one | |
| Identifiers | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.012.326 |
| EC Number |
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| KEGG | |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C23H32O3 | |
| Molar mass | 356.506 g·mol−1 |
| Appearance | White crystalline powder |
| Melting point | 171–172 °C (340–342 °F; 444–445 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Upstream sources
16-DPA can be produced from a variety of steroidal sapogenins. Industrially useful sources are diosgenin in mexican yams[1][2] and solasodine from certain nightshades. These two sapogenins can be used in a one-pot synthesis.[3] Solanidine in potato greens, an alkaloid sapogenin, is also a key source material.[4]
Downstream products
Compounds derived from 16-DPA include:
- Corticosteroids (mainly of a C22 pregnane backbone): hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate;[5]
- Progestogen (mainly of a C22 pregnane backbone): pregnenolone, progesterone*,[6] various synthetic derivatives such as medroxyprogesterone acetate* and levonorgestrel*;
- Androgens (mainly of a C19 androstane, 17-keto backbone): testosterone*[7] and esters, various synthetic derivatives;
- Estrogens (mainly of a C18 estrane, 17-hydroxy backbone): estradiol[7] and esters such as estradiol cypionate*, various synthetic derivatives such as ethinylestradiol*.
- Guggulsterone
- DHEA
- Pregnenolone 16α-carbonitrile
- Mecigestone
Those marked with a * appear on the WHO Model List of Essential Medicines, some as part of a compound medication. The list is by no means complete due to the central role of 16-DPA in steroid production.
Pharmacology
There are no current medical uses of 16-DPA. Studies in male hamsters show that the related chemical 16-DHP acts as an farnesoid X receptor (FXR) antagonist, consequently up-regulating CYP7A1 and lowering serum cholesterol. The CSIR-CDRI holds a patent over 16-DHP for prospective lipid-lowering use.[8]
History
Production of substantial quantities of steroids was not achieved until the Marker degradation in the late 1930s, a synthesis route converting diosgenin into the related compound 16-dehydropregnenolone (16-DP or 16-DHP). This reaction established Mexico as a world center of steroid production.[9] 16-DPA was produced in a variant of Marker degradation published in 1940.[6]
The earliest PubChem patent record for 16-DPA is US2656364A of 1951, describing its conversion into 17-ketosteroids.[7]
Synthesis
Lednicer covers the synthesis of 16-DPA in his book of steroids.[10] It is produced by the Marker degradation of diosgenin (which itself is a product from the hydrolysis of glycoside saponin called dioscin).[11][12] There is a large bevy of 16-DPA syntheses reported in the literature and patents (too many to record here). Notable ones that are creditworthy of mention include a one-pot synthesis[13] and a green method.[14]
Also worth mentioning is that in addition to the Marker degradation of diosgenin, it is also possible to make 16-DPA from Solasodine and Solanidine (q.v.). These derived from nightshade alkaloids and not Mexican yams.