Synthesis of nitrogen analogues of ecdysones

Abstract

This thesis is concerned with the utilization of the steroidal alkaloid solasodine (23) as a nitrogen-containing ecdysone precursor. Studies were also directed towards the preparation of nitrogen-containing ecdysone analogues from crustecdysone (8) and cholesterol (5). Preliminary synthetic studies revealed the necessity for initial protection of the secondary amino function of solasodine. It was found that acetylation of this substrate under a variety of basic conditions gave in each instance a mixture of the O,N-diacetate (34) and the isomeric Δ20(22)- and Δ22(23)-enamine triacetates (39). These latter compounds were formed as a result of ring-chain tautomerism of the spiroaminoketal moiety of solasodine. Modification of the acetylation products was studied in an effort to introduce the required ecdysone functionality. Synthetic approaches utilizing solasodine-O,N-ditosylate (35) were also investigated. These involved epoxidation, elimination, and solvolyses. The 13C n.m.r. spectra of a number of solasodine derivatives have been assigned. Oxidative cleavage of crustecdysone under a variety of conditions was investigated; best results were obtained with Jones reagent. The 2,3-glycol grouping of the resultant diketone (12) was protected as the isopropylidene and nitrogen was introduced into this compound in the form of a C-20 oxime. Proposed transformations of the oxime are suggested. Nitrogen was introduced into the nucleus of a cholestane derivative as a 2α,3α-hydroxy ρ-toluenesulphonamide. The technique of preparative HPLC was used to advantage during the above work and aspects of the technique are discussed.