Perylenequinone natural products: total syntheses of the diastereomers (+)-phleichrome and (+)-calphostin D by assembly of centrochiral and axial chiral fragments.
The first total synthesis of (+)-calphostin D and the total synthesis of (+)-phleichrome are outlined. The convergent syntheses utilize an enantiopure biaryl common intermediate, which is formed via an enantioselective catalytic biaryl coupling. The established axial chirality is transferred to the perylenequinone helical stereochemistry with good fidelity. Additionally, efforts focused on the installation of the stereogenic C7,C7'-2-hydroxypropyl groups. Three routes were evaluated to establish the C7,C7'-stereochemistry, in which the successful route involved a double epoxide alkylation with a complex axial chiral biscuprate. This strategy not only allowed the synthesis of the unnatural isomers of calphostin D and phleichrome for assessment in biological systems but also provided valuable information for the syntheses of the more complex cercosporin and hypocrellin A.
Morgan
Barbara J
BJ
Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
Mulrooney
Carol A
CA
O'Brien
Erin M
EM
Kozlowski
Marisa C
MC
D001688:Biological Products / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001688:Biological Products; D009281:Naphthalenes; D011809:Quinones; C547701:perylenequinone; D010569:Perylene; C061463:calphostin D