Structural biochemistry. IV. 3β-Hydroxy-17β-(l-prolyl)amino-androst-5-ene

Abstract

The synthesis of the title compound I11 was studied in detail and the following combination of methods was found reliable and convenient. The oxime derivative Ib of ketone Ia was reduced with sodium-ethanol to 3p-hydroxy-17/3-amino-androst-5-ene. The configurational assignment for amine IIa was supported by the results of a comparison with the 17a-epimer and by a proton magnetic resonance study of both isomers. Selective reaction between amine IIa and carbobenzoxy-L-proline was achieved with Woodward's reagent K. Of several procedures explored for removing the carbobenzoxy protecting group from amide IIc, palladiumcatalyzed hydrogenolysis proved quite satisfactory. Hydrogenolysis of carbamate IIb to yield prolyl amide 111 was realized without affecting the As olefin system. A mass spectral study of amine 111 and the corresponding 5a-derivative IV confirmed the latter observation. A brief review of procedures for the synthesis of steroidal amines was also presented.Canadian Journal of Chemistry. Volume 45, 501 (1967) T o provide synthetic steroidal peptides of possible use in advancing knowledge of both steroid transport and alteration of hormone properties, we initially developed methods for the synthesis of proline-and arginine-containing steroidal peptides derived from 3 P -h y d r o x y -1 7 0 -a m i n o -5 aandrostane (1-3). The present investigation was undertaken to develop procedures satisfactory for the synthesis of peptides derived from steroids bearing both alcohol and olefin groups. l l o r e specifically, 3P-hydroxy-A5-type steroids, which are immediate precursors of the 3-0x0-A4-system, an important characteristic of inany biologically active steroids, was of initial interest. Accordingly, the synthesis of proline derivlFor part I11 in this series, see ref.1. This paper also can be considered as part XXXVI in the series entitled Steroids and Related Natural Products.ZA preliminary report of the present study was pre- ative I11 was undertaken for the reason just outlined and for comparison with previously described (3) amide IV.Although the synthesis of an important intermediate, 17p-amine IIa, had been achieved bv sodium-ethanol reduction (4a) * , of oxime 1; or by reductive amination (4b) of ketone Ia, the need for relatively large auantities with a firmlv established stereochemistry prompted a re-study of routes to amine IIa. Among a variety of methods7 7~u c l e o~h i l i c displacement of steroid alkyl halides or p-toluenesulfonate esters was among the earliest methods employed, and the technique has recently been extended t o azide nucleophiles (5a). Catalytic reduction of steroidal oximes with palladium (5b), platinum (5c), or nickel (5d) has been used for obtaining axial amines. Lithium aluminium hydride reduction (5e) or lithium-ammonia-alcohol (5f) reduction of steroidal oximes generally yields axialequatorial mixtures. Reductive amination of steroidal ketones by application of the Leuckart reaction (5g) gives predominantly equatorial amines. Recently, Schmitt and his collaborators have ...

Steady-State Urinary Excretion Method for Determining Bioequivalence of Conjugated Estrogen Products

“…The mean of the 3-day excretion is also presented. The total endogenous levels observed were similar to values reported previously (10,11).…”

A mild and efficient palladium–triethylsilane system for reduction of olefins and carbon–carbon double bond isomerization

“…19 -22 Synthetic applications of silicon hydrides with palladium(II) have already been reported for the reduction of Schiff-bases, 23 the preparation of halosilanes, 24,25 nucleophilic substitutions at silicon atom, 26,27 and for the deprotection of aminoacids or peptides. 28,29 Ionic hydrogenation of carbon-carbon double bonds and carbonyl compounds using triethylsilane and an excess of trifluoroacetic acid has been described. 30 Polymethylhydrosiloxane (PMHS) and palladium-on-charcoal catalyst have been used for hydrogenating 1-alkenes in high yields.…”

Σχεδιασμός Και Σύνθεση Νέων Υποκατεστημένων Πυραζολοπυριδινών Και Πυριδοπυραζινών Και Μελέτη Της Κυτταροτοξικής Δράσης Τους

“…Τα υδρίδια του πυριτίου βρίσκουν εφαρμογή σε αντιδράσεις υποκατάστασης, αναγωγής και προσθήκης 504,505. Συγκεκριμένα, στη βιβλιογραφία έχει αναφερθεί η χρήση υδριδίων του πυριτίου σε συνδυασμό με παλλάδιο(ΙΙ) για την αναγωγή βάσεων του Schiff,506 τη σύνθεση αλογονοσιλανίων,507,508 την πυρηνόφιλη υποκατάσταση σε άτομο πυριτίου,509,510 καθώς και για την αποπροστασία αμινοξέων ή πεπτιδίων 511,512. Επιπλέον, είναι γνωστή η μέθοδος ιονικής υδρογόνωσης διπλών δεσμών και καρβονυλίων με τη χρήση τριαιθυλοσιλανίου σε συνδυασμό με περίσσεια τριφθοροξικού οξέος 513.…”