A model for the spiroiminal moiety of marineosins A and B was prepared starting from methylvalerolactone. Addition of vinylmagnesium bromide, protection of the alcohol, and reaction of the vinyl ketone with a protected pyrrole-2-carbonitrile N-oxide gave an isoxazoline. Hydrogenolysis of the N-O bond with Raney nickel gave a keto imine that cyclized to a hemi-iminal. O-Methylation, acid-catalyzed cleavage of the TES group and spiroiminal formation, and deprotection completed a seven-step synthesis.

A short and efficient synthesis of model spiroiminals that have the same stereochemistry but different conformations than marineosins A and B was carried out in 6-7 steps from 6-methyltetrahydropyran-2-one. These spiroiminals were also prepared biomimetically by reduction of an enol ether. A more highly substituted spiroiminal with the same stereochemistry and conformation as marineosin A was prepared in 11 steps from 6-methyl-4-propyl-3-phenyltetrahydropyran-2-one. A macrocyclic pyrrole lactone was prepared stereospecifically in 10 steps. A five step sequence converted the lactone to a late hemi-iminal intermediate that has resisted the methylation and spiroiminal formation that would lead to marineosin A.