Olivier R. Martin

Synthesis of α-amino-β-hydroxy acids using N,N-bis(trimethylsilyl)aminoketene bis(trimethylsilyl) acetal or its N-methyl-N-trimethylsilyl analog

Abstract Condensation of the title compounds with aldehydes and ketones in the presence of trimethylsilyl triflate provided the corresponding α-amino-β-hydroxy acids in fair to good yields as a mixture of diastereomers.

Synthesis of 4-seleno-d-fructose derivatives and an investigation of their utility as precursors of unsaturated hexulofuranosides

Abstract 4-Seleno- d -fructose derivatives were prepared by opening of the epoxide ring of methyl 2,3-anhydro-α- and -β- d -tagatofuranosides with phenyl selenide ion. The resulting β-hydroxyselenide system or the corresponding methansulfonate could not be induced to undergo elimination, thus providing the first examples of stable β-methylsulfonyloxyselenides. Oxidation of methyl 1,6-di- O -( tert -butyldimethylsilyl)-3- O -methylsulfonyl-4- Se -phenyl-4-seleno-α- d -fructofuranoside to the corresponding selenoxide, followed by thermally induced syn -elimination of benzeneselenenic acid, provides a convenient route to the novel unsaturated hexulofuranoside, methyl 1,6-di- O -( tert -butyldimethylsilyl)-4-deoxy-β- l - glycero -hex-4-enulofuranoside, which was readily converted into methyl 4-deoxy-α- d - threo -hexulofuranoside.

Synthetic routes from paromamine to the octodiose-containing pseudodisaccharide present in (oxy)apramycin

Abstract The synthesis of a 4- O -(2-amino-2-deoxyoctodiosyl)-2-deoxystreptamine, the first synthetic analog of the unusual pseudodisaccharide present in (oxy)apramycin was accomplished, starting from paromamine, by a two-carbon chain-elongation and a stereoselective cis -hydroxylation of the resulting E -unsaturated octuronate to give either ethyl [1- N -5,6-di- O -benzoyl-2-deoxy-1,3-di- N-p -tolysulfonylstreptamin-4-yl) 3,4-di- O -benzoyl-2-deoxy-2- p -tolylsulfonamido- d - threo -α- d - gluco - ( 12 ) or - l - threo -α- d - gluco -octo-1,5-pyranosid] uronate. Methoxide-mediated deacylation of 12 afforded in one step a bicyclic, trans -decalone-like urono-8′,4′-lactone ( 14 ) that was highly sensitive to acid-catalyzed alcoholysis and had properties in sharp contrast to those of d -glucurono-6,3-lactone. Partial reduction of lactone 14 or of the corresponding methyl octuronate 12 with lithium aluminum hydride at low temperature gave the expected α- d - threo - d - gluco -octodialdo-1,5-pyranoside-8,4-pyranose, which was methonolyzed and N -detosylated to afford the free pseudodisacchride 1-(2-deoxystreptamin-4-yl) 8-methyl (8 R , S )-2-amino-2-deoxy-α- d - threo - d - gluco -octodialdo-1,5:8,4-dipyranodioside. All of the octodiose derivatives were found to adopt a rigid, dipyranoid structure.

Syntheses of 1-(5-deoxy-β-D-arabino-hexofuranosyl)cytosine

Abstract 1-(5-Deoxy-β- d - arabino -hexofuranosyl)cytosine (4′-homoara-C) ( 11 ), a higher homolog of the antileukemic agent ara-C (1-β- d -arabinofuranosylcytosine), was prepared by two independent routes. The first one involved the inversion of configuration at C-2′ of the d - ribo epimer (1-(5-deoxy-β- d - ribo -hexofuranosyl)cytosine, 4′-homocytidine) by the diphenylcarbonate technique; the 5-deoxy- d - ribo -hexofuranosyl moiety of 4′-homocytidine was obtained by way of an anti-Markovnikov addition of iodine trifluoroacetate to the double bond of 5,6-di-deoxy-1,2- O -isopropylidene-3- O - p -tolylsulfonyl-α- d - ribo -hex-5-enofuranose and reduction of the resulting iodide(s). In the second approach, 5-deoxy-1,2- O -isopropylidene-3- O - p -tolylsulfonyl-β- d - xylo -hexofuranose was acetolyzed and condensed with 4-acetyl- N -bis(trimethylsilyl)cytosine, and alkaline treatment gave 11 by way of a 2′,3′-anhydro intermediate. The structure of 11 , in particular the configuration at C-2′, was confirmed by its 1 H- and 13 C-n.m.r. spectra.

Approach to the pseudodisaccharides present in (oxy)apramycin. Synthesis of a 4-O-amino-octodiosyl-2-deoxystreptamine from paromamine

The synthesis of an N-protected 2′-amino-2′-deoxy-1′-O-(2-deoxystreptamin-4-yl)-α-D-threo-D-gluco-octo-1′,5′:4′,8′-dipyranose in nine steps from paromamine is described; the key steps are the conversion of paromamine into a protected octuronic acid derivative, followed by its 8′,4′-lactonization upon removal of the O-protecting groups, and partial reduction of the resulting ‘trans-decalone-like’ lactone.