ABSTRACT
The first total synthesis of (-)-merrillianin (1), which is a natural sesquiterpene with a tricyclic structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereostructure determination of naturally occurring (-)-1.
ABSTRACT
Drug design using boron-containing heterocycles has attracted a great deal of attention because these compounds are believed to possess high biological activity. However, information on the synthetic methodology and pharmacokinetic profiling of boron-containing compounds is limited. In this study, we provide a new synthetic route for preparation of spiro-fused benzoxaborin derivatives and investigate their in vitro pharmacokinetic properties. Our efforts led to the successful construction of a chemical library of spiro-fused benzoxaborin derivatives with appropriate physicochemical and in vitro pharmacokinetic properties for oral drugs. These results indicate that the synthesized boron-containing compounds are therefore eligible for classification in a novel chemical library.
Subject(s)
Boron/chemistry , Drug Design , Indoles/chemical synthesis , Spiro Compounds/chemistry , Cell Membrane Permeability/drug effects , Half-Life , Humans , Indoles/pharmacokinetics , Indoles/pharmacology , Microsomes, Liver/metabolismABSTRACT
[Chemical reaction: See text] The asymmetric aldol reaction of a tetra-substituted ketene silyl acetal including an alkylseleno group with aldehydes has been developed by the promotion of Sn(OTf)2 coordinated with a chiral diamine to afford the corresponding aldols having chiral quaternary centers at the alpha-positions. The facile oxidative deselenization of these aldol compounds produces optically active alpha-methylene-beta-hydroxy esters which correspond to adducts prepared by the asymmetric Morita-Baylis-Hillman reaction.
Subject(s)
Esters , Hydroxy Acids/chemistry , Methylation , Methylene Chloride/chemistry , Models, Molecular , Molecular Conformation , Oxidation-Reduction , StereoisomerismABSTRACT
Octalactin A, an antitumor agent containing an eight-membered lactone moiety, has been stereoselectively prepared by means of enantioselective aldol reactions of selected silyl enolates with achiral aldehydes, promoted by a chiral Sn(II) complex. The medium-sized lactone part was effectively constructed by way of a new and rapid mixed-anhydride lactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) with a catalytic amount of 4-(dimethylamino)pyridine (DMAP) or 4-(dimethylamino)pyridine 1-oxide (DMAPO). The use of only 5 mol % of DMAP or 2 mol % of DMAPO rapidly promoted formation of the medium-sized ring of the octalactin, demonstrating the remarkable efficiency of the new lactonization protocol.
Subject(s)
Antineoplastic Agents/chemical synthesis , Lactones/chemical synthesis , Antineoplastic Agents/chemistry , Lactones/chemistry , Molecular Conformation , StereoisomerismABSTRACT
An efficient method for the synthesis of (+)-buergerinin F is established via the enantioselective aldol reaction of a tetra-substituted ketene silyl acetal with crotonaldehyde, followed by intramolecular Wacker-type ketalization.