Chemistry:Dimethylstilbestrol
Dimethylstilbestrol (DMS) is a nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol which was never marketed.[1][2][3][4][5]: 213 It is a so-called "weak", "impeded", or "short-acting" estrogen similarly to estriol and meso-butoestrol.[6][7][8][9] The affinity of DMS for the ER was reported as about 10% of that of estradiol.[10] For comparison, diethylstilbestrol had 140% of the affinity of estradiol for the ER.[10]
The endometrial proliferation dose of DMS in women is 20 mg.[5]: 212–213 A single 12 mg intramuscular injection of DMS has a duration of approximately 12 days in humans.[5]
Synthesis
In the old school synthesis, reaction of diacetyl with 2 molecules of phenol occurs in a manner similar to BPA (acetone was used here). Pinacol rearrangement then yields the stilbenoid. What is surprising is that if m-cresol was used instead of phenol, the resulting product had a potency 0.5 times the potency of DES, which is remarkably potent.[11]
In the newer version of the synthesis, a McMurry reaction (homodimerization) between on 4-Acetylanisole [100-06-1] and the appropriate choice of a reagent will yield 1,1'-(But-2-ene-2,3-diyl)bis(4-methoxybenzene) [895-37-4]. Demethylation of the two ethers then concludes the synthesis.[12][13]
References
- ↑ "Blastocyst Development and Implantation". The Control of Fertility. Elsevier. 3 September 2013. pp. 126–. ISBN 978-1-4832-7088-3. https://books.google.com/books?id=ehQlBQAAQBAJ&pg=PA126.
- ↑ "Anti-Estrogens". Steroidal Activity in Experimental Animals and Man. Elsevier Science. 5 December 2016. pp. 83–. ISBN 978-1-4832-7299-3. https://books.google.com/books?id=BbLfBAAAQBAJ&pg=PA83.
- ↑ "Mechanisms of Action of Estrogens". Antineoplastic and Immunosuppressive Agents. Springer Science & Business Media. 27 November 2013. pp. 110–. ISBN 978-3-642-65806-8. https://books.google.com/books?id=aU_oCAAAQBAJ&pg=PA110.
- ↑ "Antiestrogens: Mechanism of Action and Effects in Breast Cancer". Experimental Biology. Springer Science & Business Media. 14 December 2013. pp. 169–. ISBN 978-1-4757-4673-0. https://books.google.com/books?id=q9HkBwAAQBAJ&pg=PA169.
- ↑ 5.0 5.1 5.2 "Prinzipien der Hormonbehandlung: Die wichtigsten hormonalen Behandlungsmethoden". Lehrbuch der Gynäkologie. Springer-Verlag. 17 April 2013. ISBN 978-3-662-00942-0. https://books.google.com/books?id=ACybBwAAQBAJ&pg=PA213.
- ↑ "Stilbestrols and stilbestrol derivatives: estrogenic potency and temporal relationships between estrogen receptor binding and uterine growth". Molecular and Cellular Endocrinology 10 (1): 103–113. 1978. doi:10.1016/0303-7207(78)90063-1. PMID 564791.
- ↑ "Dimethylstilbestrol and 16-oxo-estradiol: anti-estrogens or estrogens?". Steroids 13 (1): 1–10. January 1969. doi:10.1016/s0039-128x(69)80055-3. PMID 5764482.
- ↑ "Oestrogen inhibitors of the stilboestrol series". The Journal of Endocrinology 18 (4): 372–380. July 1959. doi:10.1677/joe.0.0180372. PMID 13820198.
- ↑ "Dimethylstilboestrol as an oestrogen inhibitor". The Journal of Endocrinology 17 (3): 265–271. September 1958. doi:10.1677/joe.0.0170265. PMID 13587831.
- ↑ 10.0 10.1 "Estrogen-stimulated prolactin synthesis in vitro. Classification of agonist, partial agonist, and antagonist actions based on structure". Molecular Pharmacology 26 (2): 279–285. September 1984. PMID 6541293.
- ↑ "The Preparation of Synthetic Estrogens. IV. 1 Condensation of Biacetyl with Phenols". Journal of the American Chemical Society 71 (6): 2037–2041. June 1949. doi:10.1021/ja01174a039. https://pubs.acs.org/doi/abs/10.1021/ja01174a039.
- ↑ McMurry, John E.; Fleming, Michael P.; Kees, Kenneth L.; Krepski, Larry R. (1978). "Titanium-induced reductive coupling of carbonyls to olefins". The Journal of Organic Chemistry 43 (17): 3255–3266. doi:10.1021/jo00411a002.
- ↑ John E. McMurry, U.S. Patent 4,225,734 (1980 to The Regents Of The University Of California).
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