Total synthesis and properties of the crambescidin core zwitterionic acid and crambescidin 359.
The total synthesis of the crambescidin core acid 9, crambescidins 359 (8) and 431 (7), and the properties of the crambescidin core are described. A key step of the synthetic route to guanidinium carboxylate 9 is Pd(0) catalyzed cleavage of the ester side chain of pentacyclic cinnamyl ester 15. This ester is also employed to prepare a small library of crambescidin alkaloid analogues that differ in their C14 side chain. The zwitterionic guanidinium carboxylate 9 was shown to readily decarboxylate to form crambescidin 359 (8). Decarboxylation of crambescidin core acid 9 was fastest under basic conditions. In the presence of base, up to eight deuterium atoms can be incorporated into the pentacyclic crambescidin core. Both deuterium incorporation and decarboxylation of crambescidin core acid 9 are the result of facile ring opening of the spirocyclic ether rings of the pentacyclic guanidinium moiety.
Aron
Zachary D
ZD
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, California 92697-2025, USA.
Overman
Larry E
LE
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D003903:Deuterium / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry; D011485:Protein Binding; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D000470:Alkaloids; D002934:Cinnamates; D013141:Spiro Compounds; C449038:crambescidin 359; D003903:Deuterium