If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.



Where Are The Chemists?

November 3, 2014 | A version of this story appeared in Volume 92, Issue 44

It is hugely disappointing that a book review—“The Birth of the Pill: How Four Crusaders Reinvented Sex and Launched a Revolution”—describing a matter in which chemists played a principal, extensive, and crucial role, fails to mention the name of a single chemist and appears without any clarifying comment (C&EN, Sept. 22, page 32).

The Pill, and the resulting sexual revolution, would never have become a reality but for the inspired work of steroid chemists. Progesterone, the active principle produced by the corpus luteum for maintaining pregnancy, was isolated in 1934 as 20 mg of crystalline material from 625 kg of sow ovaries derived from 50,000 sows by the chemist and Nobel Laureate Adolf Butenandt. Ten years later, the pharmaceutical (medicinal) chemist Maximilian Ehrenstein made the surprising discovery that a stereoisomeric mixture of 19-norprogesterone, synthesized from strophanthidin, was a highly active progestational agent.

In 1951, Syntex chemists led by Carl Djerassi showed that stereochemically pure 19-norprogesterone derived from Birch reduction of an estrogen derivative was four to eight times more active than progesterone itself. In the same year, the Djerassi group made available for contraceptive testing 17α-ethynyl-19-nortestosterone, prepared by Birch reduction of the potent estrogen estrone methyl ether (mestranol). This Syntex oral contraceptive was marketed by Parke-Davis under the name Norlutin.

Chemists at Searle led by F. B. Colton made the corresponding 5(10) olefin “norethynodrel,” which was marketed as the oral contraceptive Enovid by Searle as a tablet containing 9.25 mg of norethynodrel and 0.15 mg of mestranol, as shown in the photo in C&EN. To drastically reduce the substantial side effects of these products, as mentioned in the review, in later years similar products were administered in much lower doses, comprising reductions of about 90% of the values shown above.

The discovery that effective oral con­traceptives actually require the combination of both a progestogen and an estrogen (mestranol) was a fortunate accident resulting from the presence of mestranol as an impurity in the progestational products of the Birch reduction of mestranol.

Manfred E. Wolff
President, Intellepharm
Laguna Beach, Calif.



This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.