16-Dehydropregnenolone acetate


16-Dehydropregnenolone acetate 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.

Upstream sources

16-DPA can be produced from a variety of steroidal sapogenins. Industrially useful sources are diosgenin in mexican yams and solasodine from certain nightshades. These two sapogenins can be used in a one-pot synthesis. Solanidine in potato greens, an alkaloid sapogenin, is also a key source material.

Downstream products

Compounds derived from 16-DPA include:
  • Corticosteroids : hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate;
  • Progestogen : pregnenolone, progesterone*, various synthetic derivatives such as medroxyprogesterone acetate* and levonorgestrel*;
  • Androgens : testosterone* and esters, various synthetic derivatives;
  • Estrogens : estradiol 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 antagonist, consequently up-regulating CYP7A1 and lowering serum cholesterol. The CSIR-CDRI holds a patent over 16-DHP for prospective lipid-lowering use.

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. This reaction established Mexico as a world center of steroid production. 16-DPA was produced in a variant of Marker degradation published in 1940.
The earliest PubChem patent record for 16-DPA is US2656364A of 1951, describing its conversion into 17-ketosteroids.

Synthesis

covers the synthesis of 16-DPA in his book of steroids. It is produced by the Marker degradation of diosgenin. There is a large bevy of 16-DPA syntheses reported in the literature and patents. Notable ones that are creditworthy of mention include a one-pot synthesis and a green method.
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. These derived from nightshade alkaloids and not Mexican yams.