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Equilenin

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Equilenin
Clinical data
Other names6,8-Didehydroestrone; Estra-1,3,5(10),6,8-pentaen-3-ol-17-one
Routes of
administration		By mouth
Drug classEstrogen
Identifiers
  • (13S,14S)-3-hydroxy-13-methyl-12,14,15,16-tetrahydro-11H-cyclopenta[a]phenanthren-17-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.007.483 Edit this at Wikidata
Chemical and physical data
FormulaC18H18O2
Molar mass266.340 g·mol−1
3D model (JSmol)
  • O=C4[C@]3(CCc1c(ccc2c1ccc(O)c2)[C@@H]3CC4)C
  • InChI=1S/C18H18O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h2-5,10,16,19H,6-9H2,1H3/t16-,18-/m0/s1 checkY
  • Key:PDRGHUMCVRDZLQ-WMZOPIPTSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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).[2] It was the first complex natural product to be fully synthesized, in work reported by 1940 by Bachmann and Wilds.[3]

Pharmacology

Pharmacodynamics

Composition of conjugated estrogens and properties of constituents
Compound Synonym Proportion (%) Relative potency
in the vagina (%)		 Relative potency
in the uterus (%)		 RBATooltip Relative binding affinity for
ERα (%)		 RBA for
ERβ (%)		 ERα / ERβ
RBA ratio
Conjugated estrogens – 100 38 100 – – –
Estrone – 49.1–61.5 30 32 26 52 0.50
Equilin Δ7-Estrone 22.4–30.5 42 80 13 49 0.26
17α-Dihydroequilin Δ7-17α-Estradiol 13.5–19.5 0.06 2.6 41 32 1.30
17α-Estradiol – 2.5–9.5 0.11 3.5 19 42 0.45
Δ8-Estrone – 3.5–3.9 ? ? 19 32 0.60
Equilenin Δ6,8-Estrone 2.2–2.8 1.3 11.4 15 20–29 0.50–0.75
17β-Dihydroequilin Δ7-17β-Estradiol 0.5–4.0 83 200 113 108 1.05
17α-Dihydroequilenin Δ6,8-17α-Estradiol 1.2–1.6 0.018 1.3 20 49 0.40
17β-Estradiol – 0.56–0.9 100 ? 100 100 1.00
17β-Dihydroequilenin Δ6,8-17β-Estradiol 0.5–0.7 0.21 9.4 68 90 0.75
Δ8-17β-Estradiol – Small amounts ? ? 68 72 0.94
Notes: All listed compounds are present in conjugated estrogen products specifically in the form of the sodium salts of the sulfate esters (i.e., as sodium estrone sulfate, sodium equilin sulfate, etc.). Sources: See template.

Chemistry

Synthesis

Total synthesis

The synthesis developed by the Bachmann group started from Butenand's ketone[4] – the 7-methoxy structural analog of 1,2,3,4-tetrahydrophenanthren-1-one[5] – and which can be readily prepared from 1,6-Cleve's acid.[6] The approach was based on well-established transformations like the Claisen condensation, the Reformatsky reaction, the Arndt–Eistert reaction, and the Dieckmann condensation.[3] Nicolaou described this preparation as ending the era preceding the post-World War II work of Robert Burns Woodward that introduced enantioselective synthesis;[4] in this synthesis, a mixture of stereoisomers were prepared and then resolved,[6] and the choice of target was partly because of the existence of only two chiral carbons and hence only four stereoisomers.[5]

The overall yield of the synthesis was 2.7% based on a twenty-step process starting from Cleve's acid.[6]

See also

References

  1. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 494–. ISBN 978-1-4757-2085-3.
  2. ^ a b Fritz, Marc A.; Speroff, Leon (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–. ISBN 978-1-4511-4847-3. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  3. ^ a b Bachmann, Werner E.; Cole, Wayne; Wilds, Alfred L. (1940). "The Total Synthesis of the Sex Hormone Equilenin and Its Stereoisomers". J. Am. Chem. Soc. 62 (4): 824–839. doi:10.1021/ja01861a036. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  4. ^ a b Nicolaou KC, Vourloumis D, Winssinger N, Baran PS (January 2000). "The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century" (PDF). Angewandte Chemie. 39 (1): 44–122. doi:10.1002/(SICI)1521-3773(20000103)39:1<44::AID-ANIE44>3.0.CO;2-L. PMID 10649349. Archived from the original (PDF) on 2017-05-17. Retrieved 2017-07-22.
  5. ^ a b Bachmann, Werner E.; Cole, Wayne; Wilds, Alfred L. (1939). "The Total Synthesis of the Sex Hormone Equilenin". J. Am. Chem. Soc. 61 (4): 974–975. doi:10.1021/ja01873a513. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  6. ^ a b c Nakanishi, Koji (1974). "Steroids". In Nakanishi, Koji; Goto, Toshio; Itô, Shô; Natori, Shinsaku; Nozoe, Shigeo (eds.). Natural Products Chemistry. Vol. 1. Academic Press. pp. 421–545. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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