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.

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 (mainly of a C22 pregnane backbone): hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate; Progestogen (mainly of a C22 pregnane backbone): pregnenolone, progesterone*, various synthetic derivatives such as medroxyprogesterone acetate* and levonorgestrel*; Androgens (mainly of a C19 androstane, 17-keto backbone): testosterone* and esters, various synthetic derivatives; Estrogens (mainly of a C18 estrane, 17-hydroxy backbone): 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 (FXR) 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 (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-ketosteroids.

Synthesis Lednicer covers the synthesis of 16-DPA in his book of steroids. It is produced by the Marker degradation of diosgenin (which itself is a product from the hydrolysis of glycoside saponin called dioscin).Marker, Russell E.; Krueger, John (1940). "Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone". Journal of the American Chemical Society 62 (12): 3349–3350. doi:10.1021/ja01869a023.Numazawa, Mitsuteru; Nagaoka, Maaso; Kunitama, Yurie (1986). "Regiospecific deoxygenation of the dihydroxyacetone moiety at C-17 of corticoid steroids with iodotrimethylsilane.". CHEMICAL & PHARMACEUTICAL BULLETIN 34 (9): 3722–3726. doi:10.1248/cpb.34.3722. ISSN 0009-2363. 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 synthesisGoswami, A.; Kotoky, R.; Rastogi, R. C.; Ghosh, A. C. (2003). "A One-Pot Efficient Process for 16-Dehydropregnenolone Acetate". Organic Process Research & Development 7 (3): 306. doi:10.1021/op0200625. and a green method.Baruah, Diganta; Das, Ram Nath; Konwar, Dilip (2015). "Facile green synthesis of 16-dehydropregnenolone acetate (16-DPA) from diosgenin". Synthetic Communications. 46(1): 79–84. doi:10.1080/00397911.2015.1121280.

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.

See also Mexican barbasco trade

References