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 A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...

steroidal

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

obtained from the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

of pregnant mares. It is used as one of the components in

conjugated estrogens Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the ...

(brand name Premarin). It was the first complex natural product to be fully synthesized, in work reported by 1940 by

Bachmann Bachmann is a surname of Switzerland and Germany. It originates as a description of the bearer as dwelling near a brook (''Bach''), such as a farm "Hofstatt am Bach" also called "Bachmanns Hofstatt" near Hinwil or Dürnten (recorded 1387), or the ...

and Wilds.

Chemistry

Synthesis

Total synthesis

The synthesis developed by the

group started from Butenand's ketone – the 7-methoxy

structural analog A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...

of 1,2,3,4-tetrahydrophenanthren-1-one – and which can be readily prepared from 1,6- Cleve's acid. The approach was based on well-established transformations like the

Claisen condensation The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone. It is named after Ra ...

, the

Reformatsky reaction The Reformatsky reaction (sometimes misspelled Reformatskii reaction) is an organic reaction which condenses aldehydes or ketones with α-halo esters using metallic zinc to form β-hydroxy-esters: The organozinc reagent, also called a 'Reforma ...

, the

Arndt–Eistert reaction In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. Named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978), the method entails treating an acid ...

, and the

Dieckmann condensation The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-keto esters. It is named after the German chemist Walter Dieckmann (1869–1925). The equivalent intermolecular reaction is the Claisen condensat ...

. Nicolaou described this preparation as ending the era preceding the post-World War II work of

Robert Burns Woodward Robert Burns Woodward (April 10, 1917 – July 8, 1979) was an American organic chemist. He is considered by many to be the most preeminent synthetic organic chemist of the twentieth century, having made many key contributions to the subject, e ...

that introduced enantioselective synthesis; 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.

References

{{Estrogen receptor modulators Sterols Phenols Estranes Estrogens Ketones

Chemistry

Synthesis

Total synthesis

See also

References