opened to the corresponding keto acid ( 102 ) by oxidation of the double
bond in ring A by means of permanganate. Reaction of that compound
with ammonia at elevated temperature can be visualized as proceeding
through an amide–enamine, such as 103. Amide interchange closes the
ring to form the enamide 104. Catalytic hydrogenation followed by
reaction with DDQ completes the synthesis ofdutasteride( 105 ).^19
CO 2 HO
100H 2 NF 3 CCF 3F 3 CCF 3O
101O HNKMnO 4F 3 CCF 3
HO 2 CO
102O HNF 3 CCF 3O NH
104O HNF 3 CCF 3
H 2 NOCH 2 N103O HNNH 32.DDQ1.H 2F 3 CCF 3O NH
105O HNVitamin D actually consists of a set of closely related compounds whose
structures are based on the steroid nucleus with an opened ring B. These
compounds control various metabolic processes from bone deposition to
skin growth. One of the vitamins (D3), calcitrol, has been used to treat
psoriasis and acne. A recent semisynthetic Vitamin D congener has
shown an improved therapeutic index over the natural product. The syn-
thetic sequence to this analogue hinges on selective scission of the isolated
double bond in the side chain. The key step thus involves inactivation of
the conjugated diene centered on ring A. This is accomplished by
formation of a Diels–Alder-like adduct between the starting material
106 , in which the hydroxyl groups are protected as the diisopropylsilyl
ether and sulfur dioxide.^20 Ozonolysis of the adduct 107 followed by
work-up of the ozonide, gives the chain-shortened aldehyde. Heating the
product restores the diene by reversing the original cylcoaddition reaction
( 108 ). The carbonyl group is then reduced to the alcohol by means of
borohydride and the resulting alcohol converted to its mesylate 109. The
chain is next homologated by first displacing the mesylate with the
anion form diethyl malonate. Saponification of the ester groups followed
by heating the product in acid cause the malonic acid to lose carbon
dioxide. Thus, the chain extended acid 110 is obtained. The carboxyl
- POLYCYCLIC COMPOUNDS: STEROIDS 37