Synthesis of macrocyclic diazanedicarboxylate and diazenedicarboxylate esters containing a steroid skeleton: an unusual oxidation of bromide to bromine by a strained diazenedicarboxylate ester. X-Ray molecular structure of 3α-(3-hydroxypropyl)-24-nor-5β-cholan-7α-ol diazane-1,2-dicarboxylate cyclic diester

Abstract

A series of diazanedicarboxylates 23–26 bridged by steroidal moieties obtained from 3α-hydroxyethyl or 3α-hydroxypropyl derivatives of 12α-hydroxy-24-norcholane or 7α-hydroxy-24-norcholane were synthesized. NMR studies showed that these diazanedicarboxylates were rapidly oxidized to the corresponding diazenedicarboxylate esters with N-bromosuccinimide (or N-chlorosuccinimide) and pyridine. Upon storage the diazenedicarboxylate esters are slowly reduced back to the diazanedicarboxylate esters with concomitant oxidation of bromide to bromine, which could be trapped with cyclohexene. Although diazenedicarboxylate 27 could be trapped by Diels–Alder reaction with cyclopentadiene to give the expected diastereoisomeric adducts 30a and 30b, aqueous work-up regenerated diazanedicarboxylate 25 and traces of ring-opened compounds including compound 29. The crystal structure of 3α-hydroxypropyl-24-nor-3β-cholan-7α-ol diazanedicarboxylate diester 26 was determined.