16-Dehydropregnenolone acetate

Chemical compound 16-Dehydropregnenolone acetate.svg 200px 20-Oxopregna-5,16-dien-3β-yl acetate (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 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 979-02-2 34163 1761683 83823 213-558-7 C14503 correct FDA 832VMW7ZGC 92855 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 MZWRIOUCMXPLKV-VMNVZBNLSA-N 23 32 3 White crystalline powder 171-172 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 us 5808117 Process for the production of 16-Dehydropregenolone acetate form diosgenin 15-09-1998 Pritish Kumar Chowdhury https://patents.google.com/patent/US5808117A/enSynthetic Communications 46 1 10.1080/00397911.2015.1121280 Diganta Baruah Ram Nath Das Dilip Konwar 98360074 2015 Facile green synthesis of 16-dehydropregnenolone acetate (16-DPA) from diosgenin 79–84 https://figshare.com/articles/journal_contribution/1609791 and solasodine from certain nightshades. These two sapogenins can be used in a one-pot synthesis.Goswami Amrit Kotoky Rumi Rastogi Romesh C. Ghosh Anil C. A One-Pot Efficient Process for 16-Dehydropregnenolone Acetate Organic Process Research & Development 1 May 2003 7 3 306–308 10.1021/op0200625 https://core.ac.uk/download/pdf/234671756.pdf Solanidine in potato greens, an alkaloid sapogenin, is also a key source material. Arkivoc The synthesis of 16-dehydropregnenolone acetate (DPA) from potato glycoalkaloids Vronen Patrick J.E. Nadeshda Koval Aede de Groot 2003 2004 2 24–50 10.3998/ark.5550190.0005.203 http://www.arkat-usa.org/get-file/19135/ free 2027/spo.5550190.0005.203 free Downstream products Compounds derived from 16-DPA include: Corticosteroids (mainly of a C22 pregnane backbone): hydrocortisone*, betamethasone*, dexamethasone*, beclometasone*, fluticasone, and prednicarbate;Chemistry and Pharmacology of Naturally Occurring Bioactive Compounds 13.4.7 The Crystal Structure of Dehydropregnolone Acetate: A Pregnane CRC Press 308 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.Ramakrishna Rachumallu Kumar Durgesh Bhateria Manisha Gaikwad Anil Nilkanth Bhatta Rabi Sankar 16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters The Journal of Steroid Biochemistry and Molecular Biology 1 April 2017 168 110–117 10.1016/j.jsbmb.2017.02.013 28232149 30520080 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.Russell Marker and the Mexican Steroid Hormone Industry https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html American Chemical Society June 5, 2012 16-DPA was produced in a variant of Marker degradation published in 1940.Marker RE, Krueger J Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone J. Am. Chem. Soc. 62 12 3349–3350 1940 10.1021/ja01869a023 1940JAChS..62.3349M The earliest PubChem patent record for 16-DPA is US2656364A of 1951, describing its conversion into 17-ketosteroids.Hershberg Emanuel B. Oliveto Eugene P. Process for the manufacture of 17-keto steroids https://patents.google.com/patent/US2656364A 20 October 1953 Synthesis Lednicer covers the synthesis of 16-DPA in his book of steroids.Lednicer, D. 2011 Steroid chemistry at a glance Wiley Chemistry at a glance 1. publ 978-0-470-66084-3 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 Category:Acetate esters Category:Steroids