Equilenin Explained
Equilenin, also known as 6,8-didehydroestrone, as well as estra-1,3,5(10),6,8-pentaen-3-ol-17-one, is a naturally occurring steroidal estrogen obtained from the urine of pregnant mares.[1] [2] It is used as one of the components in conjugated estrogens (brand name Premarin). It was the first complex natural product to be fully synthesized, in work reported by 1940 by Bachmann and Wilds.[3]
Chemistry
Synthesis
Total synthesis
The synthesis developed by the Bachmann group started from Butenand's ketone - the 7-methoxy structural analog of 1,2,3,4-tetrahydrophenanthren-1-one[4] - and which can be readily prepared from 1,6-Cleve's acid.[5] The approach was based on well-established transformations like the Claisen condensation, the Reformatsky reaction, the Arndt–Eistert reaction, and the Dieckmann condensation. Nicolaou described this preparation as ending the era preceding the post-World War II work of Robert Burns Woodward that introduced enantioselective synthesis;[6] in this synthesis, a mixture of stereoisomers were prepared and then resolved, and the choice of target was partly because of the existence of only two chiral carbons and hence only four stereoisomers.
The overall yield of the synthesis was 2.7% based on a twenty-step process starting from Cleve's acid.
See also
- List of estrogens § Equine estrogens
Notes and References
- Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 494–.
- Book: Fritz MA, Speroff L . Clinical Gynecologic Endocrinology and Infertility. 28 March 2012. Lippincott Williams & Wilkins. 978-1-4511-4847-3. 751–.
- The Total Synthesis of the Sex Hormone Equilenin and Its Stereoisomers . Bachmann WE, Cole W, Wilds AL . Werner Emmanuel Bachmann . Alfred L. Wilds . . 1940. 62. 4. 824–839. 10.1021/ja01861a036.
- The Total Synthesis of the Sex Hormone Equilenin . Bachmann WE, Cole W, Wilds AL . Werner Emmanuel Bachmann. Alfred L. Wilds. J. Am. Chem. Soc.. 1939. 61. 4. 974–975. 10.1021/ja01873a513.
- Book: Nakanishi K . Steroids . Nakanishi K, Goto T, Itô S, Natori S, Nozoe S . Natural Products Chemistry. 1 . Academic Press. 1974. 421–545 . 9781483218861. https://books.google.com/books?id=PKb-BAAAQBAJ&pg=PA491.
- Nicolaou KC, Vourloumis D, Winssinger N, Baran PS . The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century . Angewandte Chemie . 39 . 1 . 44–122 . January 2000 . 10649349 . 10.1002/(SICI)1521-3773(20000103)39:1<44::AID-ANIE44>3.0.CO;2-L . 2017-07-22 . dead . https://web.archive.org/web/20170517074054/http://yxzx.zjnu.edu.cn/lunwen/8.pdf . 2017-05-17 . K. C. Nicolaou .
