Geoffrey Stemp

The action of diethylaminosulphur trifluoride (dast) on trans-4-amido- 3-Chromanols: Preparation of cis-amidoalcohols via oxazolines

Treatment of a variety of trans-4-amido-3-chromanols (3) with DAST gives oxazolines (4) which can be hydrolysed to give the corresponding cis-amido-alcohols (5). Similar treatment of the trans-4-ureido-3-chromanol (8) gave the unexpected 4-fluoro-3-ureidochromanol (9) as the major product.

ASYMMETRIC COPPER-CATALYSED ALKENE CYCLOPROPANATION AND AZIRIDINATION USING TARTRATE-DERIVED BIS-OXAZOLINE LIGANDS

Abstract The enantioselective cyclopropanation and aziridination of styrene using chiral tartrate-derived bis-oxazoline ligands 1, 6, and 7 is reported. The effects of variation of the size of the oxazoline substituent (R1) and the size of the diazoacetate ester substituent (R2) on the level and sense of enantioselection is described.

Hydrogen bonding control in the oxidative cyclisation of 1,5-dienes

Abstract The regioselective dihydroxylation of a series of functionalised polyenes is described. Under acidic conditions, the osmate ester derivatives obtained from oxidation with OsO 4 /TMEDA undergo an intramolecular cyclisation reaction forming functionalised tetrahydrofurans with high stereoselectivity and in good yield. The generality of this method is illustrated with an application to the synthesis of a bis-tetrahydrofuran ring system.

A syn selective dihydroxylation of cyclic allylic trichloroacetamides using catalytic osmium tetroxide

A range of cyclic allylic trichloroacetamides has been synthesised. Dihydroxylation utilising catalytic osmium tetroxide and quinuclidine-N-oxide monohydrate as the re-oxidant in dichloromethane yields diols with good levels of syn selectivity.

Stereoselective synthesis of protected amines and diamines from alkenes using N,N-Dichloro-t-butylcarbamate

N,N-Dichloro-t-butylcarbamate (1) reacts with alkenes (2) in a regio- and stereo-selective manner to give the trans-chlorocarbamate adducts (3). Treatment of (3) with base gives aziridines (5), and reaction of (3) and (5) with sodium azide leads selectively to the versatile diamine precursors (6) and (7).In situ reduction of (3) with Zn/NH4OAc leads directly to Boc-protected amines (10).

N-(substituted-phenyl) piperazines: antagonists with high binding and functional selectivity for dopamine D4 receptors

Abstract A series of N-(substituted-phenyl) piperazine derivatives was prepared as selective antagonists of the dopamine D 4 receptor. Many analogues possessed a binding selectivity of over 100 fold for D 4 over D 2 receptors. In functional studies in the microphysiometer, compound 24 showed a selectivity over dopamine D 2 receptors of greater than 1000 fold.

Heterocyclic analogues of 2-aminotetralins with high affinity and selectivity for the dopamine D3 receptor

A novel series of 5,6,7,8-tetrahydroquinazolines, 4,5,6,7-tetrahydroindazoles and 4,5,6,7-tetrahydrobenzothiazoles has been prepared, having high affinity and selectivity for the dopamine D3 receptor. The 4-methoxy-5,6,7,8-tetrahydroquinazoline 6i and 2-amino-4,5,6,7-tetrahydrobenzothiazole 8 proved to be agonists with among the highest D3 receptor affinities and selectivities reported to date.

Benzopyran potassium channel activators related to cromakalim - heterocyclic amide replacements at position 4.

Abstract The synthesis and antihypertensive activity in spontaneously hypertensive rats (SHR) of a series of benzopyran potassium channel activators related to cromakalin (1) where the pyrrolidinone at position 4 is replaced by a number of potential heterocyclic amide and ester bioisosteres is reported. Aminotriazole 6 was shown to be the most potent amide replacement in this series.

Novel 2,3,4,5-tetrahydro-1H-3-benzazepines with high affinity and selectivity for the dopamine D3 receptor.

Starting from the dopamine D3 receptor antagonist SB-277011 1, a series of 2,3,4,5-tetrahydro-1H-3-benzazepines has been identified with high affinity for the dopamine D3 receptor and selectivity over the D2 receptor. The 3-acetamido-2-fluorocinnamide derivative 20 gave high D3 receptor affinity (pKi 8.4) with 130-fold selectivity over the 2, receptor.

A novel series of 2-aminotetralins with high affinity and selectivity for the dopamine D3 receptor

Abstract A novel series of N-[4-(4-Phenylbenzoylamino)butyl]-1,2,3,4-tetrahydro-2-naphthylamines with high affinity and selectivity for the dopamine D3 receptor has been prepared. The 5-cyclopropylmethyloxy 3j, methanesulfonyloxy 3k and trifluoromethanesulfonyloxy 3l derivatives represent some of the highest affinity (pKis 8.6–8.9) and most selective (200–320-fold) dopamine D3 receptor antagonists reported to date.