Total synthesis of (-)-crambidine and definition of the relative configuration of its unique tetracyclic guanidinium core.
Total syntheses of the 3S,8S,10S,19R,43S isomer 4a and the 3S,8S,10S,19R,43R isomer 4b of the unique crambescidin alkaloid crambidine are reported. These studies confirm the tetracyclic structure proposed by Braekman and co-workers for crambidine, and establish the rel-3R,8R,10R,19S relative configuration for this moiety. Natural crambidine is most likely the 3S,8S,10S,19R,43S isomer 4a. These syntheses were completed in five steps and approximately 14% overall yield from 1-iminohexahydro[1,2-c]pyrimidine carboxylic ester 10, an intermediate in our earlier total synthesis of 13,14,15-isocrambescidin 800 (3). The signature step in the total syntheses of crambidine and several stereoisomers is chemoselective dehydrogenation of the tethered Biginelli adduct 10 or the derived tetracyclic intermediate 17. Additionally, these studies reveal the unprecedented ring-chain isomerization of the crambidine ring system exemplified by the interconversion of isomers 15a and 15b.
Overman
Larry E
LE
Contribution from the Department of Chemistry, 516 Rowland Hall, University of California-Irvine, Irvine, CA 92697-2025, USA. leoverma@uci.edu
Rhee
Young Ho
YH
D000470:Alkaloids / Q000138:chemical synthesis*; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000470:Alkaloids; D013141:Spiro Compounds; C490355:crambescidin 800; C507639:crambidine; C083155:crambescidin 816; D019791:Guanidine