Enantioselective Total Synthesis of Batzelladine F and Definition of Its Structure.

Abstract

Batzelladine F (1) was synthesized in enantioselective and stereoselective fashion in 15 steps (longest linear sequence) and 1.7% overall yield from two readily available enantioenriched β-hydroxy esters, methyl (R)-3-hydroxydecanoate and methyl (R)-3-hydroxybutyrate. Tethered Biginelli condensations are used to assemble both tricyclic guanidine fragments, with the second tethered Biginelli condensation (14 + 16 → 17) also being employed to join the guanidine fragments. Three diastereomers of batzelladine F, 2−4, were prepared also. A combination of HPLC, optical rotation and CD spectroscopy was employed to distinguish stereoisomers 1−4, proving that 1 is the correct structure of the hexacyclic marine alkaloid batzelladine F.

Amidines and Guanidines in Natural Products and Medicines

“…On the other hand, batzelladines F-I (39-42) induced a dissociation of a p56ck-CD4 binding complex[77]. The structures of batzelladines A (34), D (37)[78] and F (39)[79] have been revised (revised structures are shown inFigure 10.10). Recently, ptilomycalin D (43)[80], batzelladines J (44)[81] and K-N (45-48)[82] have been isolated from sponges Monanchona dianchora and M. unguifera, respectively(Figure 10.10).…”

“…Recently, ptilomycalin D (43)[80], batzelladines J (44)[81] and K-N (45-48)[82] have been isolated from sponges Monanchona dianchora and M. unguifera, respectively(Figure 10.10). Total syntheses of batzelladines were recently reported[79,83,84].…”