Enantioselective total synthesis of batzelladine F and definition of its structure.
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 beta-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.
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, 92697-2025, USA.
Frederick
F
Cohen
Larry E
LE
Overman
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002942:Circular Dichroism; D003651:Decanoates / Q000737:chemistry; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006885:Hydroxybutyrates / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D003651:Decanoates; D006885:Hydroxybutyrates; C444860:batzelladine F; C016579:2-methyl-3-hydroxybutyric acid; D019791:Guanidine