title: Towards the synthesis of proanthocyanidins: half a century of innovation.
abstract: Results emanating from the synthesis of proanthocyanidins played a crucial role in defining the constitution, regiochemistry, and absolute configuration of this complex but fascinating group of plant secondary metabolites. The initial efforts, commencing in 1966, were focused on structure elucidation of, especially, the procyanidins, profisetinidins, and prorobinetinidins. However, over the past 12 years the emphasis has shifted to the synthesis of the bioactive procyanidins and some of their derivatives at a scale that would permit assessment of their pharmacological properties. With a few exceptions, the vast majority of these synthetic protocols involve the formation of the interflavanyl bond by acid/Lewis acid activation at C-4 of a flavan-3,4-diol or its equivalent, and subsequent trapping of the incipient C-4 carbocation by the nucleophilic centers of a flavan-3-ol (catechin). This review represents the first comprehensive chronicle depicting the development of the subject of proanthocyanidin synthesis.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA. dferreir@olemiss.edu
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.forename: Christina M
authors.initials: CM
authors.lastname: Coleman
mesh_terms: D044946:Biflavonoids / Q000138:chemical synthesis*; D002392:Catechin / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000266:history / Q000379:methods*; D005419:Flavonoids / Q000737:chemistry*; D049673:History, 20th Century; D049674:History, 21st Century; D058116:Lewis Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010944:Plants / Q000737:chemistry; D044945:Proanthocyanidins / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014934:Wood / Q000737:chemistry
chemical_list: D044946:Biflavonoids; D005419:Flavonoids; D058116:Lewis Acids; D044945:Proanthocyanidins; C404987:flavan-3-ol; C017674:procyanidin; D002392:Catechin; C001532:leucocyanidin