Scalable total synthesis and biological evaluation of haouamine A and its atropisomer.
A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.
Burns
Noah Z
NZ
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Krylova
Irina N
IN
Hannoush
Rami N
RN
Baran
Phil S
PS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013237:Stereoisomerism; D000097566:Cyclophanes
D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; C474767:haouamine A; D000097566:Cyclophanes