Synthetic approaches for the synthesis of a cytostatic steroidal B-D bilactam.
A new synthetic procedure and a modification of the original method described in the literature for the synthesis of the steroidal B-D bilactam, 3 beta-hydroxy-7 alpha,17 alpha-diaza-B,D-dihomo-5-androsten-7,17-dione are reported. The key step in the modified method involved protection of the D-lactamic nitrogen atom of 3 beta-acetoxy-17 alpha-aza-D-homo-5-androsten-17-one using a reagent of specific electrophilicity (due to the stereoelectronic properties of the cyclic amide), as Beckmann rearrangement of the B-steroidal ring was hindered, possibly via long range effects, by the presence of the unprotected D-lactamic moiety. Using the 3 beta-acetoxy-5-androsten-17-one as starting material, a new synthetic procedure was developed through ketalization of the 17-ketone and allylic oxidation to the 7-ketone, which was subsequently followed by Beckmann rearrangement of the B- and D-steroid rings. Both approaches resulted in 45 and 67% yields of the desired B,D-bilactam, respectively, in contrast to the 15% yield, which has been reported in the literature.
Koutsourea
Anna I
AI
Laboratory of Pharmaceutical Chemistry, School of Health Sciences, Department of Pharmacy, University of Patras, 26500 Patras, Greece.
Arsenou
Evaggelia S
ES
Fousteris
Manolis A
MA
Nikolaropoulos
Sotiris S
SS
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007769:Lactams / Q000737:chemistry; D010091:Oximes / Q000737:chemistry
D007202:Indicators and Reagents; D007769:Lactams; D010091:Oximes; D000735:Androstenedione