Steroid synthesis, Barton nitrite photolysis

In a second example, Ryu and co-workers [87, 88] demonstrated the nitrite photolysis (Barton reaction) of the steroidal substrate 157 to afford 158 (Scheme 6.41), a key intermediate in the synthesis of an endothelin receptor antagonist, using a 300 W high-pressure mercury lamp. Maintaining a gap of 7.5 cm between the stainless-steel/glass reactor [channel dimensions = 1000 pm (width) x 107 pm (depth) x 2.2 m (length)] and the light source, an acetone solution of the nitrite... 

In a similar manner, 11/3-nitrites, on photolysis, attack Ci to furnish the corresponding oximes which, upon nitrous acid treatment, gave 18-oxygenated steroids. The most spectacular application of the Barton reaction has been a three-step synthesis of aldosterone.12 Irradiation of corticosterone-11-nitrite (27, R = NO), followed by nitrous acid treatment, gave aldosterone (29) in 15% overall yield. Comparable conversions of 11/3-hydroxyprogesterone to 21-desoxyaldosterone12 and A1-corticosterone to A aldosterone14 have also been achieved. 

Schemes 5 and 6 outline the functionalization of a 10/1-Me by a steroidal 6/f-ol [1] and a 2/3-61 nitrite [6], Functionalization of 13/i-Me by a 20a-ol nitrite [7] and functionalization in the terpenoid field [8] are outlined in Schemes 7 and 8. The last example involves a 7-membered cyclic transition state that seldom occurs. Scheme 9 outlines a recent application of the Barton reaction in the synthesis of a biologically active carbacepham [9]. The photolysis of acyclic 5-phenyl-1-pentanol nitrite gives, preferentially, a nitroso dimer arising as a result of the abstraction of a hydrogen attached to the d-carbon, rather than the e-carbon from which the better stabilized benzyl radical can be generated (Scheme 10) [10].

Cycloartenol is the parent compound of a family of triterpenoids characterized by a 9, 10—cyclopropane ring, and has been suggested as an important intermediate in the biosynthesis of tetracyclic triterpenoids and steroids in plants. A key feature of the synthesis of cycloartenol by Barton etai is functionalization of the unactivated C-19 methyl group in lanosterol by photolysis of an 11/3-nitrite (A), followed by an intramolecular alkylation for closure of the cyclopropane ring. 

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