The Syntheses of Cyclic Spermine Alkaloids: Analogues of Buchnerine and Budmunchiamine C

The syntheses of two macrocyclic spermine alkaloids, analogues 1 and 2 of budmunchiamine C and buchnerine, in which N,N′‐bis(2‐aminoethyl)hexane‐1,6‐diamine (PA 262; 4 ) replaces spermine as polyamine backbone, were accomplished by two different methods. The first synthetic approach was based on a metal‐template intramolecular amidation of tetraamino esters prepared from a Michael addition of protected PA 262 10 to ethyl hexadec‐2‐ynoate ( 12 ) and ethyl prop‐2‐ynoate 17 , respectively (see Schemes 4 and 5, resp.). The consecutive Michael addition of ethane‐1,2‐diamine to unsaturated esters and aminolysis was employed in the second synthetic approach to prepare the precursors 23 and 24 (Scheme 6). The macrocyclic lactams were then constructed by macrocyclization of sulfonamido derivatives 25 and 26 in DMF with Cs₂CO₃ as catalyst.