David I. Smith

Enhancing the yield and diastereoselectivity of the Pictet-Spengler reaction : a highly efficient route to cis-1,3-disubstituted tetrahydro-β-carbolines

Abstract Under conditions of kinetic control, the cis-diastereoselectivity of the Pictet-Spengler reaction between tryptophan esters and aldehydes can be controlled by varying the size of the ester group; the reaction proceeds in essentially quantitative yield with most aldehydes when conducted in chloroform in the presence of molecular sieves.

Spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Spiro 2-pyrrolidin-5-ones were obtained from N-substituted succinimides by a two-step procedure, involving 5- or 6-endo-trig cyclisation of N-acyliminium ion intermediates with a tethered aromatic π-nucleophile.

Novel spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Abstract Several spiro 2-pyrrolidin-5-ones were obtained by a two-step procedure from N -substituted succinimides, involving spiro cyclisation of N -acyliminium ion intermediates in refluxing trifluoroacetic acid; in all cases cyclisation utilised a tethered aromatic π-nucleophile, and ring-closure followed 5- or 6- exo-trig pathways.

N-bridged heterocycles. Part 5. αω-Bis-(2-oxobenzimidazolinyl)alkanes and -ethers as selective ligands for group-1 and -2 metals

A series of the title compounds (10), (12), and (13) and several analogues were synthesised from the readily available 1-isopropenylbenzimidazolin-2-one. Various substituents were attached to the unsubstituted nitrogen atoms of the benzimidazolinone moieties and the series of products obtained were tested for their complexing ability with group-1 and -2 metal-salts. The isolation of crystalline complexes, the solubilisation of the salts in chloroform by the ligand, the i.r. carbonyl absorption shift, and the ion-transport ability of the ligand were examined as an index of complexation. Selective complexation, particularly for calcium, was noted in several cases.

Assembly intermediates in polyketide biosynthesis: enantioselective syntheses of beta-hydroxycarbonyl compounds.

A versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of acyloxazolidinone using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable intermediates in the synthesis of 4-hydroxy-6-substituted delta-lactones.

A general synthesis of homochiral β-hydroxy N-acetylcysteamine thioesters

Abstract A convenient and efficient route for the enantioselective synthesis of functionalised β-hydroxy N -acetylcysteamine thioesters is described. The route allows the facile incorporation of vicinal 13 C labelling to produce intermediates required for biosynthetic studies on a wide range of polyketide metabolites, e.g. 6-MSA, monocerin, colletodiol and strobilurins.

Stereospecific reduction of a β-keto-nitrile : formation of a single indolic β-hydroxy-nitrile from a mixture of tautomers and diastereoisomers

Abstract The β-keto-nitrile 2, which is an advanced intermediate for the synthesis of several indole alkaloids, is composed of a mixture of enol/keto tautomers, and of diastereoisomers; nevertheless, reduction with sodium borohydride yields essentially a single diastereoisomer 3.

A new asymmetric route to bridged indole alkaloids: formal syntheses of (–)-suaveoline, (–)-raumacline and (–)-Nb-methylraumacline

When the homologated nitrile 11 derived from L-tryptophan undergoes a modified Pictet–Spengler reaction with methyl propynoate, the resulting cis-tetrahydro-β-carboline 12a is ideally functionalised for cyclisation to the bridged ketonitrile 14; simple functional group modification via the nitrile 15(structure confirmed by X-ray crystallography) allow convergence with the tetracyclic α,β-unsaturated aldehyde 10, which is an advanced intermediate for the synthesis of a range of bridged indole alkaloids.

New asymmetric route to bridged indole alkaloids: formal enantiospecificsyntheses of (-)-suaveoline, (-)-raumaclineand(-)-Nb-methylraumacline

The homologous nitrile 13 derived from L-tryptophan undergoes a modified Pictet–Spengler reaction with methyl propynoate, under conditions of kinetic control, to afford the cis-tetrahydro-β-carboline 15a (cis∶trans = 77∶23). After protection, Dieckmann–Thorpe cyclisation to the bridged keto nitrile 20 proceeds in 90% yield. Simple functional group modifications via the alcohol 21a and nitrile 22 (structures confirmed by X-ray crystallography) allow convergence with the tetracyclic α,β-unsaturated aldehyde 10, which is an advanced intermediate for the synthesis of a range of bridged indole alkaloids.

Practical syntheses of [13C]- and [14C]-labelled glucosphingolipids

Synthetic routes to [glucose-U-14C]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine 1b and to [glucose-13C6]-1-O-(β-D-glucopyranosyl)sphingosine ([glucose-13C6]glucopsychosine, 2b) are described. Whereas the protected ceramide precursor for 1b was prepared using conventional methodology, two new strategies were developed in the course of the synthesis of 2b. Of these, one relies on keeping a protecting group in place at all times to avoid the handling difficulties associated with sphingosine 4, while the other generates a protected derivative (24) of sphingosine indirectly by means of a Mitsunobu inversion.