{{short description|Chemical compound}} {{Chembox | ImageFile = 16-Dehydropregnenolone acetate.svg | ImageSize = 200px | ImageAlt = | IUPACName = 20-Oxopregna-5,16-dien-3β-yl acetate | SystematicName = (3a''S'',3b''R'',7''S'',9a''R'',9b''S'',11a''S'')-1-Acetyl-9a,11a-dimethyl-3a,3b,4,6,7,8,9,9a,9b,10,11,11a-dodecahydro-3''H''-cyclopenta[''a'']phenanthren-7-yl acetate | OtherNames = 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 |Section1={{Chembox Identifiers | CASNo = 979-02-2 | ChEBI = 34163 | ChEMBL = 1761683 | ChemSpiderID = 83823 | EC_number = 213-558-7 | KEGG = C14503 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 832VMW7ZGC | PubChem = 92855 | StdInChI=1S/C23H32O3/c1-14(24)19-7-8-20-18-6-5-16-13-17(26-15(2)25)9-11-22(16,3)21(18)10-12-23(19,20)4/h5,7,17-18,20-21H,6,8-13H2,1-4H3/t17-,18-,20-,21-,22-,23+/m0/s1 | StdInChIKey = MZWRIOUCMXPLKV-VMNVZBNLSA-N }} |Section2={{Chembox Properties | C=23 | H=32 | O=3 | Appearance = White crystalline powder | Density = | MeltingPtC = 171-172 | BoilingPt = | Solubility =}} }}
'''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<ref>{{cite patent | country = us | number = 5808117 | status = | title = Process for the production of 16-Dehydropregenolone acetate form diosgenin | pubdate = | gdate = 15-09-1998 | inventor = Pritish Kumar Chowdhury | url = https://patents.google.com/patent/US5808117A/en }}</ref><ref>{{cite journal |journal=Synthetic Communications |volume=46 |issue=1 |doi=10.1080/00397911.2015.1121280 |first1=Diganta |last1=Baruah |first2=Ram Nath |last2=Das |first3=Dilip |last3=Konwar |s2cid=98360074 |year=2015 |title= Facile green synthesis of 16-dehydropregnenolone acetate (16-DPA) from diosgenin |pages=79–84 |url=https://figshare.com/articles/journal_contribution/1609791 }}</ref> and solasodine from certain nightshades. These two sapogenins can be used in a one-pot synthesis.<ref>{{cite journal |last1=Goswami |first1=Amrit |last2=Kotoky |first2=Rumi |last3=Rastogi |first3=Romesh C. |last4=Ghosh |first4=Anil C. |title=A One-Pot Efficient Process for 16-Dehydropregnenolone Acetate |journal=Organic Process Research & Development |date=1 May 2003 |volume=7 |issue=3 |pages=306–308 |doi=10.1021/op0200625|url= https://core.ac.uk/download/pdf/234671756.pdf}}</ref> Solanidine in potato greens, an alkaloid sapogenin, is also a key source material.<ref>{{cite journal |journal= Arkivoc |title=The synthesis of 16-dehydropregnenolone acetate (DPA) from potato glycoalkaloids |last1= Vronen |first1=Patrick J.E. |first2=Nadeshda |last2=Koval |first3=Aede |last3=de Groot |year=2003 |volume=2004 |issue=2 |pages=24–50 |doi=10.3998/ark.5550190.0005.203 |url=http://www.arkat-usa.org/get-file/19135/ |doi-access=free |hdl=2027/spo.5550190.0005.203 |hdl-access=free }}</ref>
== Downstream products == Compounds derived from 16-DPA include: * Corticosteroids (mainly of a C22 pregnane backbone): hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate;<ref> {{cite book |title=Chemistry and Pharmacology of Naturally Occurring Bioactive Compounds |chapter=13.4.7 The Crystal Structure of Dehydropregnolone Acetate: A Pregnane |publisher=CRC Press |page=308 }}</ref> * Progestogen (mainly of a C22 pregnane backbone): pregnenolone, progesterone*,<ref name="Marker1940"/> various synthetic derivatives such as medroxyprogesterone acetate* and levonorgestrel*; * Androgens (mainly of a C19 androstane, 17-keto backbone): testosterone*<ref name=17k/> and esters, various synthetic derivatives; * Estrogens (mainly of a C18 estrane, 17-hydroxy backbone): estradiol<ref name=17k/> 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.<ref>{{cite journal |last1=Ramakrishna |first1=Rachumallu |last2=Kumar |first2=Durgesh |last3=Bhateria |first3=Manisha |last4=Gaikwad |first4=Anil Nilkanth |last5=Bhatta |first5=Rabi Sankar |title=16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=1 April 2017 |volume=168 |pages=110–117 |doi=10.1016/j.jsbmb.2017.02.013|pmid=28232149 |s2cid=30520080 }}</ref>
== 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.<ref name="Marker Degradation: Creation of the Mexican Steroid Hormone Industry">{{cite web|title=Russell Marker and the Mexican Steroid Hormone Industry|url=https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html|publisher=American Chemical Society|access-date=June 5, 2012}}</ref> 16-DPA was produced in a variant of Marker degradation published in 1940.<ref name="Marker1940">{{cite journal |vauthors=Marker RE, Krueger J | title = Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone | journal = J. Am. Chem. Soc. | volume = 62 | issue = 12 | pages = 3349–3350 | year = 1940| doi = 10.1021/ja01869a023 | bibcode = 1940JAChS..62.3349M }}</ref>
The earliest PubChem patent record for 16-DPA is US2656364A of 1951, describing its conversion into 17-ketosteroids.<ref name=17k>{{cite web |last1=Hershberg |first1=Emanuel B. |last2=Oliveto |first2=Eugene P. |title=Process for the manufacture of 17-keto steroids |url=https://patents.google.com/patent/US2656364A |date=20 October 1953}}</ref>
==Synthesis== Lednicer covers the synthesis of 16-DPA in his book of steroids.<ref>{{cite book |author=Lednicer, D. | date= 2011 | title=Steroid chemistry at a glance | publisher=Wiley | series=Chemistry at a glance | edition=1. publ | isbn=978-0-470-66084-3}}</ref> It is produced by the Marker degradation of diosgenin (which itself is a product from the hydrolysis of glycoside saponin called dioscin).<ref>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.</ref><ref>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.</ref> 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<ref>Goswami, 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.</ref> and a green method.<ref>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.</ref>
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 == <references/>
{{DEFAULTSORT:Dehydropregnenolone acetate, 16-}} Category:Acetate esters Category:Steroids