title: Total Synthesis of (±)-Glyceollin II and a Dihydro Derivative.
abstract: Stressed soybeans produce a group of phytoalexins that belong to the 6a-hydroxypterocarpan family of flavonoids. Certain of the more prominent members, such as the glyceollins I, II, and III, have demonstrated potential antidiabetic properties and promising cytotoxicity in both human breast and prostate cancer cell cultures with preliminary studies in animals further demonstrating antitumor effects in estrogen-dependent, human breast cancer cell implants. Although syntheses of glyceollin I have been reported previously, this work constitutes the first total directed synthesis of (±)-glyceollin II. It involves 12 steps with an overall yield of 7% using practical methods that should be readily scalable to produce quantities needed for advanced biological characterization. Highlights include a novel intramolecular benzoin condensation, a chelation-controlled lithium aluminum hydride-mediated reduction, and an intramolecular cyclization via the formation of a transient epoxide intermediate to cap the construction of the 6a-hydroxypterocarpan system. Additionally, a dihydro analogue has been obtained, and several isolated intermediates have been made available for evaluation of their biological properties and possible contributions toward elaborating key structure-activity relationship data among this family of promising phytoalexins elicited from stressed soybeans.
authors.affiliation: Center for Molecular Innovation and Drug Discovery, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Neha
authors.initials: N
authors.lastname: Malik
authors.affiliation: Center for Drug Design and Development, Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo , Toledo, Ohio 43606, United States.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Drug Design and Development, Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo , Toledo, Ohio 43606, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Erhardt
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans; D001943:Breast Neoplasms / Q000188:drug therapy; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy; D036343:Pterocarpans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes; D013025:Glycine max / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000094162:Phytoalexins
chemical_list: C507789:6a-hydroxypterocarpan; D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D004967:Estrogens; D006576:Heterocyclic Compounds, 4 or More Rings; D036343:Pterocarpans; D012717:Sesquiterpenes; C000591133:glyceollin II; D000094162:Phytoalexins