ABSTRACT
Bromination of 17-O-acetyltestosterone (17beta-acetoxyandrost-4-en-3-one) (1) was performed with 1, 5, and 10 eq of Br2 in AcOH-Et2O at room temperature. In all cases 2alpha,6beta- (2) and 2alpha,6beta-dibromo-17beta-acetoxyandrost-4-en-3-one (3) were obtained, although the yields were dependent upon the conditions used. Bromination of compound 1 with 10 eq of Br2 in the presence of silver trifluoromethanesulfonate (silver triflate, AgOTf) at room temperature for 12 h gave 2,7alpha-dibromo- (4) and 2,4,7alpha-tribromo-17beta-acetoxy-3-hydroxy-1-methylestra-1,3,5(10)-triene-6-one (5). The formations of the products were inferred on the basis of products obtained under controlled brominations of 1 in the presence of AgOTf, and of those obtained by the brominations of compounds 9-13 also in the presence of AgOTf.
Subject(s)
Bromine/chemistry , Mesylates/chemistry , Testosterone/analogs & derivatives , Testosterone/chemistry , Magnetic Resonance SpectroscopyABSTRACT
Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. Structural analyses of sapogenins and saponins derived from pseudo derivatives 11, 12, 18 and 19 were performed by comparisons of their 1H-NMR spectral data and the X-ray analytical data of 3-O-p-bromobenzoyl sarsasapogenin 7, 3-O-acetyl diosgenin 13 and saponin 20. The mechanisms of ring-closure reaction of the side chain at C-22 of pseudosapogenins and pseudosaponins were deduced using stereomodels of the spirostanols derived from 11 under various reaction conditions. Inhibitory activities of saponin diglycosides 3, 4, 20, 21 and 25 on human platelet agglutinations induced by ADP and ristocetin were compared.
Subject(s)
Glycosides/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Saponins/chemistry , Spirostans/chemical synthesis , Adenosine Diphosphate/pharmacology , Crystallography, X-Ray , Glycosides/pharmacology , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Structure , Platelet Aggregation Inhibitors/pharmacology , Ristocetin/pharmacology , Spirostans/pharmacology , Sterols/chemical synthesis , Sterols/pharmacologyABSTRACT
17-O-Acetyl testosterone, which has no susceptible hydroxyl or carboxyl group for glycosylation, was glycosylated with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide in the presence of a mixed catalyst, Hg(CN)2 and HgBr2, in benzene-nitromethane. Reaction occurred on the alpha, beta-unsaturated ketone on the six-membered A-ring to give six 3-O-glycosides, each bearing a cyano group at the 3- or 5-position of the aglycon, and a 3-O-glycoside bearing a CONH2 group at the 3-position. Structural analyses of these products were carried out by various NMR (1H, 13C NMR, 1H-1H and 1H-13C COSY, HMBC, and DEPT), FABMS and X-ray analyses. The mechanisms of the formations of the products are discussed. It was determined that mercuric cyanide was essential as a catalyst for the progress of the cyanoglycosylation.
