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Organic Chemistry, Synthesis 507

when separation and structural elucidation was the princi-
pal object, organic chemists have been interested in natural
products. Rapidly, however, the synthesis of these mate-
rials came to be of importance, in part to verify proposed
structural assignments and, of increasing importance to-
day,topreparequantitiesofnaturalmaterialswithinterest-
ing pharmacological properties otherwise available only
in very limited amounts. The preparation of natural com-
pounds has also had a significant impact on the theory of
organicchemistry,forexample,theprincipleoftheconser-
vation of orbital symmetry may have resulted in part from
insights developed during the synthesis of vitamin B-12.
In this section, several examples have been taken from the
synthesis of steroids and prostaglandins to illustrate the
development of synthetic strategy.

A. Steroids
The early work of Robinson on the synthesis of the steroid
nucleus may be contrasted with the elegant Woodward ap-
proach to the total synthesis of steroids. Robinson’s ap-
proach requires the masterful manipulation of function-
ality so that through the course of the synthesis, relay
compounds may be reached. Relay compounds are ma-
terials reached by alternate pathways, frequently by the
degradation of a readily available natural product. The
Robinson synthesis of androsterone, which spanned sev-
eral years, required four stages, each stage comprised of
numerous steps. The first stage was the transformation
of 2,5-dihydroxynapthalene to the Reich diketone. The
second stage was the transformation of the Reich dike-
tone to the Koester and Logemann (KL) ketone. The third
stage was the transformation of the KL ketone to dimethyl
aetioallobilianate benzoate. The fourth required the con-
version of dimethyl aetioallobilianate benzoate to andros-
terone. Both the KL ketone and aetioallobilianic acid were
available from natural materials (Fig. 1).
In contrast to the lengthy manipulation of functional-
ity to facilitate relay synthesis, Woodward’s synthesis of
methyl d,l-3-keto- 4,9(11). 16-etiocholatrienoate is con-
siderably shorter and illustrates an advance in synthetic
strategy. This efficient approach relies strongly on an un-
derstanding of stereochemical relationships and the effi-
cient choice of functionality (Fig. 2).
FIGURE 1 Robinson synthesis of androsterone. (a) Sodium
B. Prostaglandins methoxide, dimethyl sulfate; (b) sodium, ethanol; (c) sodium
methoxide, methyl iodide; (d) diethylaminobutanone, methyl io-
The prostaglandins are a closely related family of com- dide, potassium; (e) hydrogen iodide; (f) platinum oxide, hydro-
pounds discovered as early as 1930 but whose structure gen; (g) palladium–strontium carbonate, hydrogen; (h) sodium
was not determined until the 1960s. These compounds triphenyl methide, carbon dioxide; (i) diazomethane; (j) ethyl bro-
had a variety of physiological effects, but were only avail- moacetate, zinc; (k) platinum oxide, hydrogen; (l) phosphorous
oxychloride; (m) platinum oxide, hydrogen; (n) potassium hydrox-
able in very minute quantities. As such they were ideal
ide, methanol; (o) oxalyl chloride; (p) diazomethane; (q) silver
targets for synthesis. Biosynthetic analysis has shown nitrate; (r) potassium hydroxide, methanol; (s) acetic anhydride;
that fatty acids, in particular arachidonic acid, are the (t) heat.