Synthesis of the louisianin alkaloid family via a 1,2,4-triazine inverse-electron-demand Diels-Alder approach.

Isolated in 1995, the four members of the louisianin family (A, B, C and D) are simple pyridine and 2-pyridone alkaloids that display both antibacterial and anticancer activity. Herein we describe the synthesis of all four members of the louisianin family, from a conveniently prepared 1,2,4-triazine and via a common tetrasubstituted pyridine intermediate. This study includes the synthesis of louisianin B in both racemic form and as the (-)-enantiomer.

Concise and practical synthesis of C-glycosyl ketones from sugar benzothiazoles and their transformation into chiral tertiary alcohols.

[Reaction: see text]. A collection of 13 unsymmetrical ketones, each one featuring a sugar (d-glucosyl, d-galactosyl, d-mannosyl, and l-fucosyl) and an aglycone moiety (phenyl, 2-thiazolyl, TMS-ethynyl, allyl, and 1-propenyl) was prepared by a uniform route based on the use of benzothiazole as a carbonyl group equivalent. Succinctly, C-glycosylbenzothiazoles readily prepared by addition of 2-lithiobenzothiazole to sugar lactones and deoxygenation, were subjected to a one-pot reaction sequence involving N-methylation of the heterocyclic ring by MeOTf, treatment of the N-methylbenzothiazolium salt with a Grignard reagent, and HgCl(2)-promoted hydrolysis of the benzothiazoline thus formed. The resulting ketones were isolated in yields varying from 35 to 80%. Treatment of the sugar ketones with various organometals containing the phenyl, 2-thiazolyl, TMS-ethynyl, or ethynyl group as a substituent afforded chiral tertiary alcohols. These addition reactions were highly stereoselective as observed by crude NMR analysis and isolation of a single epimer in high yield in each case examined. However, because of the complexity of the reagents involved, the stereochemical outcome of these reactions appears to be difficult to rationalize by simple classical steric models, thus, ab initio studies taking into account the role of the sugar fragment are advisable. An interesting synthetic elaboration of a propargylic alcohol containing the thiazole ring into a propargylic alcohol bearing the formyl and carboxylate groups is reported.

Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their utility in the assembly of C-fucosides of biological relevance.

An efficient synthesis of O-benzylated derivatives of the title sugar aldehydes via thiazole addition to tri-O-benzyl-l-fuconolactone followed by highly stereoselective deoxygenation of the resulting thiazolylketose and thiazole to formyl transformation is described. Wittig olefination of these aldehydes with galactopyranose and glucopyranose 6-phosphoranes and reduction of the resulting alkenes afforded alpha- and beta-linked (1-->6)-L-C-fucosyl disaccharides, namely, beta-L-C-Fuc-(1-->6)-alpha-D-Gal, alpha-L-C-Fuc-(1-->6)-alpha-D-Gal, and alpha-L-C-Fuc-(1-->6)-alpha-d-Glc. The alpha-anomer of the above C-fucosyl aldehydes was transformed into a C-fucosylmethyl triphenylphosphonium iodide from which the corresponding C-fucosylmethylene phosphorane was generated upon treatment with BuLi. This phosphorane reacted with the Garner aldehyde (N-Boc D-serinal acetonide) and its one-carbon higher homologue to give alkenes whose reduction and unveiling of the glycinyl group from the oxazolidine ring afforded C-fucosyl alpha-amino acids, namely alpha-L-linked C-fucosyl serines and C-fucosyl asparagines. As a final test of the synthetic utility of the title aldehydes, the beta-anomer was employed as starting material in the stereoselective synthesis of both R- and S-epimer L-C-fucosyl phenylhydroxy acetates. One epimer was obtained by reaction of the sugar aldehyde with phenylmagnesium bromide, oxidation of the resulting alcohol to ketone, addition of 2-lithiothiazole to the latter, and transformation of the thiazole ring into the carboxyl group through an aldehyde intermediate. The other epimer was obtained by the same procedure and inverting the timing of phenyl and thiazolyl group addition. In both routes, the key step establishing the configuration of the quaternary carbon atom of the aliphatic chain was the highly stereoselective addition of the organometal to the ketone intermediate.