title: Synthetic endeavors toward 2-nitro-4-alkylpyrroles in the context of the total synthesis of heronapyrrole C and preparation of a carboxylate natural product analogue.
abstract: The synthesis of 2-nitro-4-oligoprenyl-substituted pyrrole derivatives relevant to the heronapyrroles and related natural products was investigated. Among numerous approaches, nitration of a 3-farnesyl-substituted unprotected pyrrole using AcONO2 gave the best results, albeit still with unsatisfactory yield and regioselectivity. Therefore, the synthesis of (-)-heronapyrrole C acid, an analogue of the naturally occurring antibiotic heronapyrrole C carrying a bioisosteric carboxylate in place of the nitro group, was examined. In lieu of the unsatisfactory nitration, a regioselective acylation with Cl3CCOCl was carried out (>8:1 regioselectivity, in contrast to the 1:1.3 ratio for the nitration). The trichloromethyl ketone was converted to the desired acid in a haloform reaction at the final stage of the synthesis. Further key steps of the analogue synthesis involved a position- and stereoselective Corey-Noe-Lin dihydroxylation and an organocatalytic double Shi epoxidation. A biomimetic polyepoxide cyclization cascade established the bis-THF backbone. Thus, (-)-heronapyrrole C acid was synthesized in eight steps (14.5% overall yield) from commercially available starting materials.
authors.affiliation: Fachbereich Chemie, Institut für Organische Chemie, Universität Hamburg , Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schmidt
authors.forename: Christian B W
authors.initials: CB
authors.lastname: Stark
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D032701:Biomimetics; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001688:Biological Products; D002264:Carboxylic Acids; D009574:Nitro Compounds; D011758:Pyrroles; C554880:heronapyrrole C