ABSTRACT
In 1998, Hayashi and Miyaura reported the first asymmetric conjugate addition of aryl- and alkenyl-boronic acids to α,ß-unsaturated ketones using chiral rhodium complexes as catalysts. During the last decade, this reaction has been developed quickly and the enantioselectivity was significantly improved with the emergence of new phosphine ligands. In addition to the methodological work, this reaction was applied as a key step in the total synthesis of natural compounds. The purpose of this paper focuses on examples of the use of this reaction to prepare elaborated chiral molecules with high diastereoselectivies and/or enantioselectivities.
Subject(s)
Organic Chemicals/chemistry , Organic Chemicals/chemical synthesis , Rhodium/chemistry , Catalysis , Chemistry Techniques, Synthetic , StereoisomerismABSTRACT
In this Letter, the synthesis and the evaluation of the cytotoxicity of new hemiasterlin analogues were reported. The indole moiety was replaced respectively by benzofurane, naphthalene and 4-bromobenzene groups. Most of these derivatives possess strong cytotoxic activity on two human tumour cell lines (KB and Hep-G2), and some analogues showed comparable cytotoxic activity to that observed for paclitaxel and ellipticine, against KB and Hep-G2 cancer cell lines.
Subject(s)
Cytotoxins/chemistry , Cytotoxins/toxicity , Oligopeptides/chemistry , Oligopeptides/toxicity , Cell Death/drug effects , Drug Screening Assays, Antitumor/methods , Hep G2 Cells , Humans , StereoisomerismABSTRACT
In this Letter, we report a convenient and efficient method for the synthesis of new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,ß-unsaturated aryl groups as Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB and Hep-G2 cancer cell lines comparable to paclitaxel and ellipticine.
Subject(s)
Oligopeptides/chemical synthesis , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , KB Cells , MCF-7 Cells , Oligopeptides/chemistry , Oligopeptides/pharmacology , Structure-Activity RelationshipABSTRACT
[reaction: see text]. A new strategy to access the fumagillin/fumagillol skeleton is proposed. An Evans aldolization and a RCM involving an enone are used for the preparation of a key cyclohexanone intermediate, which was readily converted to fumagillol. The synthesis also features an efficient preparation of isogeraniol and isogeranic acid.
