Medicinal Chemistry

(Jacob Rumans) #1

contain oxygen-based functional groups (terpenoids). The 1939 Nobel Prize in chemistry
was awarded to Leopold Ruzicka for his pioneering work on the chemistry of terpenes,
agents that have been used as therapeutics since antiquity. By steam distilling various
plant materials, mixtures of odoriferous compounds, known as essential oils, were obtained;
terpenes are the most important constituents of these oils. Although they exhibit tremen-
dous diversity, all terpenes are structurally related according to the isoprene rule of
Ruzicka. They arise from a head-to-tail joining of 5-carbon isoprene (2-methyl-1,3-
butadiene) units; carbon-1 is the head, carbon-4 is the tail. Terpenes are then classified
by the number of constituent isoprene units: monoterpenes are 10-carbon compounds
biosynthesized from two isoprene units; sesquiterpenes are 15-carbon molecules from
three isoprene units. α-Pinene contains two isoprene building blocks assembled into a
complex cyclic structure.
Historically, terpenes have enjoyed a role as symptom-relieving therapeutics.
Camphor and carvone (spearmint oil) have been used as soothing agents in the past
history of pharmaceutical compounds. More recently, the role of terpenes in bio-
chemistry has been more fully appreciated. β-Carotene, for example, may be cleaved
into two units of vitamin A. Other terpenes, such as geraniol, are now recognized as
pheromones (a chemical secreted by one individual of a given species in order to elicit
a response in another individual of the same species). Pheromones are of interest in
medicinal chemistry for a variety of indications; for instance, attractant pheromones can
be used for the control of insects known to spread human disease.


8.1.4.5 Lipids: Steroids


Steroids are important lipids whose structures are based on a tetracyclic system. Most
steroids function as hormone chemical messengers, and thus these molecules have been
discussed in detail in chapter 5. Structurally, steroids are heavily modified triterpenes
that are biosynthesized starting from the acyclic hydrocarbon squalene and progressing
through cholesterol to the final steroid product; Bloch and Cornforth, who were
awarded Nobel Prizes in medicine (1964), contributed greatly to the elucidation of this
remarkable biosynthetic transformation.
Cholesterolis the prototypic steroid lipid. It was first isolated in 1770; in the 1920s,
the German chemists Windaus and Wieland deduced the structure for cholesterol,
receiving Nobel Prizes for their work in 1927 and 1928. Cholesterol is important in
medicinal chemistry, not only for its role in atherosclerosis, but also because it is an
important lipid in membrane structure.
The remaining steroid lipids constitute two main classes of steroid hormones: sex
hormones and adrenocortical hormones. The sex hormones include androgens (testos-
terone, androsterone), estrogens (estrone, estradiol), and progestins (progesterone). The
adrenocortical hormones include mineralocorticoids (aldosterone) and glucocorticoids
(hydrocortisone).


8.1.5 Carbohydrates

Carbohydrates are naturally occurring compounds that typically have the general
formula Cx(H 2 O)y, reflecting the fact that they appear to be “hydrates of carbon.”


474 MEDICINAL CHEMISTRY

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