Margarita Jurczak

Synthesis of polyhydroxyindolizidines from 5,6-dihydro-2H-pyran-2-one.

(1aR,5aR,5bS,6S,7S)-6,7-Di-tert-butoxy-5-oxo-pyrrolidino[1,2-b]isoxazolidino[4,5-c]tetrahydropyran (8) prepared by (1,3)-dipolar cycloaddition of the cyclic nitrone 6 derived from tartaric acid to 5,6-dihydro-2H-pyran-2-one (7) was transformed into indolizidine 11 via a sequence of reactions involving methanolysis of the lactone ring, intramolecular alkylation of the nitrogen atom promoted by a carbontetrabromide-triphenylphosphine mixture and hydrogenolysis of the N single bond O bond. Decarboxylation of 11 provided known 7-hydroxylentiginosine derivative 14, whereas oxidative decarboxylation gave indolizidine 15 structurally related to castanospermine.

Synthesis of pyrrolizidine alkaloids via 1,3-dipolar cycloaddition involving cyclic nitrones and unsaturated lactones

The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.

1,3-Dipolar cycloaddition of a nitrone derived from (S)-malic acid to α,β-unsaturated δ-lactones

Abstract 1,3-Dipolar cycloaddition of nitrone 7 to α,β-unsaturated δ-lactones: non-chiral 2, racemic mixture 3/3ent, d -glycero 3 and d -threo 15 proceeds with high stereoselectivity in the case of 2 and 15, and with a significant kinetic resolution in the case of the racemate 3/3ent. The endo approach of reactants was not observed. CD-spectroscopy proved an attractive tool for determination of the absolute configuration of cycloadducts.

Diastereoselection in 1,3-dipolar cycloadditions of a chiral cyclic nitrone to α,β-unsaturated δ-lactones

Abstract 1,3-Dipolar cycloadditions of the nitrone 1 to α,β-unsaturated δ-lactones: non-chiral 13 , racemic mixture 3 / 4 , d - glycero 3 , and l - glycero 4 proceed with high stereoselectivity in the cases of 13 and 3 and a significant kinetic resolution in the case of the racemate 3 / 4 . The exo approach to the re – re sides of the lactones predominates.

Design of antimicrobially active small amphiphilic peptide dendrimers.

Novel polyfunctional small amphiphilic peptide dendrimers characterized by incorporation of a new core compounds – tris-amino acids or tetrakis-amino alcohols that originated from a series of basic amino acids – were efficiently synthesized. These new core elements yielded molecules with multiple branching and (+5)/(+6) charge at the 1-st dendrimer generation. Dendrimers exhibited significant antimicrobial potency against Gram(+) and Gram(-) strains involving also multiresistant reference strains (S. aureus ATCC 43300 and E. coli ATCC BAA-198). In addition, high activity against fungi from the Candida genus was detected. More charged and more hydrophobic peptide dendrimers expressed hemolytic properties.

Double Asymmetric Induction in 1,3‐Dipolar Cycloaddition of Nitrones to 2,3‐Unsaturated Sugar 1,5‐Lactones

1,3‐Dipolar cycloaddition of nitrones 1–3 to the α,β‐unsaturated δ‐lactones, non‐chiral 4, d‐glycero 5, dl‐glycero 5/5ent, d‐erythro 6, and d‐threo 7, provides an interesting example of a double asymmetric induction. In all cases, only the exo approach of reactants was observed. The high preference of anti addition of the nitrones to the terminal acetoxymethyl group in the lactones 5–7 is consistent with previous observations, and can be explained in terms of the axial approach of the nitrone oxygen atom. The 3‐t‐butoxy group of the nitrone plays a similar role. In the case of mismatched pairs, the location of the 4‐acetoxy substituent in the lactone and that of the 4‐t‐butoxy one in the nitrone become decisive for the outcome of the addition. CD‐spectroscopy proved to be an attractive tool to determine the absolute configuration of the cycloadducts. †This paper is dedicated to Professor Gérard Descotes on the occasion of his 70th birthday.

Stereocontrolled entry to negamycin from d-glucose

Conjugate addition-rearrangement of N-benzylhydroxy-lamine to lactone 6 provides isoxazolidin-5-one 7 which was in turn mesylated at the hydroxy group and subjected to the next skeleton rearrangement to afford 3,5-disubstituted isoxazolidine 10. Standard transformation of 10 gave negamycin lactone 4.

Oxidation of Glycals with Hydrogen Peroxide

Tri-O-acetyl-D-glucal (8) treated with a mixture of hydrogen peroxide–molybdenum trioxide undergoes a Ferrier rearrangement to form 2,3-unsaturated anomeric hydroperoxides 14 and 15. Tri-O-acetyl-D-galactal (10) and tri-O-benzyl-D-glucal (9), under the same conditions, afford the hydroperoxides in a low yield, whereas tri-O-benzyl-D-galactal (11) does not produce any unsaturated hydroperoxide. 2,3-Unsaturated anomeric hydroperoxides of α- and β-D-erythro- and α-D-threo-19, -20, and -24, respectively, were used for the enantioselective epoxidation of prochiral allylic alcohols 25-27 and oxidation of sulfides 28 and 29 to give stereoselectivities of up to 50% enantiomeric excess.

Synthesis of acosamine and daunosamine from sugar σ-enelactones

Abstract Conjugate addition-rearrangement of N -benzylhydroxylamine to lactones 11 and 12 provided respective isoxazolidin-5-ones 13 and 14 which were in turn mesylated at the hydroxy group and subjected to the next skeleton rearrangement to afford N ,3,4,5-tetrasubstituted isoxazolidines 18 and 19 in such a way that inversion of configuration at C-5 of the sugar chains occured. Standard transformation of isoxazolidines 18 and 19 provided methyl glycoside of N,O -diacetate of acosamine 33 and daunosamine 34 , respectively.

Synthesis of 2,3‐Dihydroxy‐1‐Epilupinine

The 1,3‐dipolar cycloaddition of unsaturated D‐threo‐hexaldonolactone 3 and a six‐membered cyclic nitrone 11 led to a single adduct 15, which could be transformed into (1S, 2S, 3S, 9aS)‐2,3‐dihydroxy‐1‐hydroxymethyl‐quinolizidine 28 related to epilupinine via a reaction sequence involving rearrangement of the six‐membered lactone ring into a five‐membered one, removal of the terminal carbon atom from the sugar chain, cleavage of the N‐O bond, and the intramolecular alkylation of the nitrogen atom.