Evolution of a strategy for the synthesis of structurally complex batzelladine alkaloids. Enantioselective total synthesis of the proposed structure of batzelladine F and structural revision.
Stereoselective synthesis of octahydro-5,6,6a-triazaacenaphthalenes 29 and 34 having the anti-relationship of the angular hydrogens flanking the pyrrolidine nitrogen confirmed suspicions that the relative configuration of the left-hand tricyclic guanidine fragment of batzelladine F should be revised to have the syn relationship of these hydrogens. Several strategies were examined for coupling tricyclic guanidine fragments to prepare potential structures for batzelladine F. Eventually, a convergent synthesis strategy was devised, whose central step was a fragment-coupling tethered-Biginelli reaction (Scheme 17). Using this approach we synthesized four potential structures of batzelladine F, 35-38. None of these compounds, nor their enantiomers, were identical to natural batzelladine F. Reinvestigation of mass spectra of natural batzelladine F, and fragments 88 and 89 obtained upon saponification of batzelladine F, demonstrated that the originally proposed connectivity of this alkaloid was also incorrect. The revised connectivity, 90, of natural batzelladine F depicted in Scheme 21 is proposed.
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, 92697-2025, USA.
Frederick
F
Cohen
Larry E
LE
Overman
D000073:Acenaphthenes / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D009281:Naphthalenes / Q000138:chemical synthesis; D013237:Stereoisomerism
D000073:Acenaphthenes; D000470:Alkaloids; D009281:Naphthalenes; C444860:batzelladine F; D019791:Guanidine