The purified isomer ( 84 )^14 is currently used in the clinic as a treatment for
endometriosis, as well as other conditions related to excess progesterone
stimulation.
The total synthesis based 17-ethyl norgonane, levonorgestrel ( 85 ), has
been in use for many years. The corresponding oxime has recently been
introduced as the progestational component of an oral contraceptive. In
the absence of a specific reference, it may be speculated that the compound
norelgestimate( 86 ), is prepared by simply reactioning 85 with hydroxyl-
amine in analogy to the preparation of the corresponding 17 acetoxy
derivative.^15
OHO
85OHHON
86B. Corticosteroid Related Compounds
The soybean sterols that comprise one of the principal sources for proges-
tins and corticoids consist almost entirely of a mixture of stigmasterol and
sitosterol. The lack of a double bond in the side chain renders the latter
useless as a starting material since that function is key to the Upjohn
process for removing the long terpinoid side chain present in these
sterols. As a result, tonnage quantities of this steroid thus accumulated in
a Kalamazoo storage lot over the years. A microorganism was finally
found in the late 1970s that would feed on this rich source of carbon, meta-
bolizing the fatty side chain at the 17 position and at the same time intro-
ducing an oxygen function at position 9 that could be used later to
introduce the crucial double bond in ring C. Considerable work was then
devoted to developing methods for building up the highly functionalized
two-carbon side chains found in corticoids at the now bare 17 position
found in these biodegradation products. One of the intermediates from
one of those schemes has interestingly recently becomes a drug in its
own right. Wet macular degeneration, one variant of the disease that
leads to loss of vision with age, is marked by excessive growth of new
blood vessels in the retina. This process, neovascularization, in effect
destroys photoreceptor areas of the retina. The drug, anecortave( 95 ),
which needs to be administered locally within the eyeball, inhibits the
34 ALICYCLIC COMPOUNDS