David Tanner

An aziridine route to chiral β-lactams a novel entry to (+)-thienamycin

Abstract Enantiomerically pure 2,3- epoxy alcohols are transformed readily and stereospecifically to the corresponding aziridines, regioselective ring-opening of which allows subsequent conversion to chiral β-lactams suitable for elaboration to the title antibiotic.

From aziridines to carbapenems via a novel β-lactam ring closure: an enantioselective synthesis of (+)-PS-5

Abstract An enantioselective synthesis of the carbapenem antibiotic (+)-PS-5 is described. The starting point is the chiral Sharpless epoxy-alcohol 3 which is transformed stereospecifically to the aziridine 6 . Regioselective ring-opening of 6 by LiEt2Cu followed by RuO4 oxidation yields the β-sulfonamido carboxylic acid 8 which is cyclised under mild conditions and in excellent yield to the N-tosyl azetidinone 9 . Deprotection at nitrogen, unmasking of the side-chain hydroxyl and oxidation then furnishes 11 , a known advanced intermediate for (+)-PS-5.

A mild and efficient method for the preparation of n-tosyl amides and lactams

Abstract N-tosyl amides and lactams can be prepared easily and under mild conditions by the inter- or intramolecular condensation of carboxylic acids and secondary sulfonamides. The coupling reagent used is dicyclohexyl-carbodiimide (DCC) in the presence of 4-pyrrolidinopyridine (4-PPY) and the reactions proceed readily, usually in high yield, at room temperature.

Enantioselective total synthesis of ingramycin

Abstract An enantioselective total synthesis of the 14-membered macrolide antibiotic ingramycin, 1 , is described. In a convergent approach three chiral fragments A , B and C are assembled, the allylic bromide A deriving its chirality from L -serine while the asymmetric centres in sulfones B and C are introduced via the Sharpless enantioselective epoxidation technique. After coupling of these fragments and a highly efficient macrolactonisation (82% yield) a final deprotection step furnishes the target compound.

[2,2] (4,4′)Trans-stilbenophane

Abstract The title compound has been synthesised by a reductive coupling of bibenzyl-4,4′- dicarbaldehyde and its dynamic properties and photoinduced isomerisations are briefly described.

Enantioselective total synthesis of (+)-negamycin

Abstract An efficient enantioselective total synthesis of the antibiotic (+)-negamycin is described, the absolute stereochemistry deriving from ( R )-(+)-malic acid and subsequent use of the Sharpless asymmetric epoxidation reaction.

New routes to perhydrohistrionicotoxin

Abstract Two stereocontrolled routes to the alkaloid depentylperhydrohistrionicotoxin 3 , are described. The key steps are alkylation, with retention of configuration, of the iodide 8 and the mesylate 12 , respectively. A tricyclic aziridinium species is proposed as the reactive intermediate in the latter reaction. The synthesis of 3 represents a formal total synthesis of the title alkaloid.

Simple camphor derivatives as chiral auxiliaries for asymmetric conjugate addition

Abstract The chiral enoates, 4 , readily available in two simple steps from (+)-camphor, Undergo asymmetric conjugate addition with the Gilman reagent LiBu2Cu. Chemical yields are high (70–90%) and in the case of the naphthyl-substituted enoate 4e excellent diastereoselectivity (95% d.e. ) is observed. 3-Methyl-heptan-l-ol of correspondingly high enantiomeric purity is obtained by reduction of the conjugate adduct with lithium aluminium hydride.

NMR studies of conformations and dynamic processes—III : Cyclophanes with unsaturated bridges

Abstract Three cyclophanes, each displaying a different type of dynamic process, have been studied by NMR methods. The barriers to these processes are attributed mainly to the decrease in π-electron overlap between the benzene rings and adjacent double bonds which occurs in the transition state for each process. In [5 2 ] paracyclophanetetraene, two successive flippings of the benzene rings interconvert the two hydrogens in the methylene groups (Scheme 1). In tetramethyl [2 4 ] paracyclophanetetraene, the passage of one methyl group through the central cavity of the molecule interconverts two conformations of similar, but not equal, free energy (Scheme 2). In [2 6 ] orthoparacyclophanehexaene, the orthosubstituted rings change sides by passing through the centre of the cyclophane (Scheme 3).

1,6:9,14-bismethano[16]annulene - a new bridged [4n]annulene

Abstract The molecular structure and dynamic behaviour of the bridged [4n] annulene 1,6:9,14-bismethano-[16]annulene is unravelled by NMR and X-ray investigations, combined with force field calculations.