16-Dehydropregnenolone acetate (16-DPA) is a chemical compound used as an intermediate or synthon in the production of many semisynthetic

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

s. As

7-ACA 7-ACA (7-aminocephalosporanic acid) is the core chemical structure (a synthon) for the synthesis of cephalosporin antibiotics and intermediates. It can be obtained by chemoenzymatic hydrolysis of cephalosporin C. See also * 6-APA 6-APA ((+)- ...

is for cephalosporins and 6-APA is for penicillins, 16-DPA is for 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

sapogenin Sapogenins are the aglycones, or non-saccharide, portions of the family of natural products known as saponins. Sapogenins contain steroid or other triterpene frameworks as their key organic feature. For example, steroidal sapogenins such as tigge ...

s. Industrially useful sources are

diosgenin Diosgenin, a phytosteroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of ''Dioscorea'' wild yam species, such as the Kokoro. The sugar-free (aglycone) product of such hydrolys ...

in mexican yams and solasodine from certain nightshades. These two sapogenins can be used in a

one-pot synthesis In chemistry a one-pot synthesis is a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one reactor. This is much desired by chemists because avoiding a lengthy separ ...

. Solanidine in potato greens, an alkaloid sapogenin, is also a key source material.

Downstream products

Compounds derived from 16-DPA include: *

Corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s (mainly of a C22 pregnane backbone): hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate; *

Progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

(mainly of a C22 pregnane backbone): pregnenolone,

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

*, various synthetic derivatives such as

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...

* and

levonorgestrel Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand name Plan B One-Step among ...

*; * Androgens (mainly of a C19 androstane, 17-keto backbone): testosterone* and esters, various synthetic derivatives; * Estrogens (mainly of a C18

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

, 17-hydroxy backbone): estradiol and esters such as estradiol cypionate*, various synthetic derivatives such as ethinylestradiol*. 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.

Pharamacology

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 The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high levels ...

(FXR) antagonist, consequently up-regulating

CYP7A1 Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enz ...

and lowering serum cholesterol. The CSIR-CDRI holds a patent over 16-DHP for prospective lipid-lowering use.

History

Production of substantial quantities of

s was not achieved until the

Marker degradation The Marker degradation is a three-step synthetic route in steroid chemistry developed by American chemist Russell Earl Marker in 1938–40. It is used for the production of cortisone and mammalian sex hormones (progesterone, estradiol, etc.) from p ...

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. 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-ketosteroid 150px, Androstenedione 150px, Androsterone 150px, Estrone A ketosteroid, or an oxosteroid, is a steroid in which a hydrogen atom has been replaced with a ketone (C=O) group. A 17-ketosteroid is a ketosteroid in which the ketone is located spe ...

References

{{DEFAULTSORT:Dehydropregnenolone acetate, 16- Acetate esters Steroids