Barbara Szechner

Synthesis of methyl 2,3-dideoxy-DL-alk-2-enopyranosides from furan compounds : A general approach to the total synthesis of monosaccharides

Abstract A method of converting furan derivatives via 2,3-dideoxy- DL -alk-2-enopyranos-4-uloses, a new class of sugar compounds, into methyl 2,3-dideoxy- DL -alk-2-enopyranosides is described. Furfuryl alcohol, 2(1,2-O-isopropylidene-1,2-dihydroxyethyl)furan, 1(2-furyl)ethanol and 2(2-furyl)glycerol 1,3-diacetate treated with bromine in methanol gave corresponding 2,5-dimethoxy-2,5-dihydrofuran derivatives, which hydrolyzed with diluted sulphuric acid afforded 2,3-dideoxy- DL -pent-2-enopyranos-4-ulose, 2,3-dideoxy- DL -hex-2-enopyranos-4-ulose, 2,3,6-trideoxy- DL -hex-2-enopyranos-4-ulose and 6-O-acetyl-5C-acetoxymethyl-2,3-dideoxy- DL -hex-2-enopyranos-4-ulose, respectively. The latter treated with methyl orthoformate in the presence of Lewis acids yielded corresponding methyl glycosides, which were reduced with sodium borohydride to give appropriate pairs of stereoisomeric methyl 2,3-dideoxy- DL -alk-2-enopyranosides. All stereoisomers were separated and their configuration was established by PMR spectra. 1-O-Acetyl derivatives of 2,3-dideoxy- DL -alk-2-enopyranos-4-uloses were obtained.

Stereoselective synthesis of methyl β-dl-novioside

Abstract Stereoselective synthesis of an antibiotic sugar, methyl β- dl -novioside from 2-(2-furyl)propan-2-ol is described. The key step involved transformation of 2,5-dimethoxy-2,5-dihydrofuran derivative into 2,3-unsaturated pyranos-4-ulose. Its glycosidation followed by reduction, methylation and hydroxylation afforded β- dl -novioside. It has been demonstrated that anomeric configuration of methyl noviosides and novobiocin are opposite to that reported in the literature.

Total synthesis of racemic methyl 2,3-anhydro-6-deoxyhexopyranosides

Abstract All the stereoisomeric methyl 2,3-anhydro-6-deoxy- DL -hexopyranosides and/or their 4- O -acetyl derivatives have been prepared from methyl 2,3,6-trideoxy- DL -hex-2-enopyranosides or their 4- O -acetyl derivatives by epoxidation with hydrogen peroxide-benzonitrile. P.m.r. data for the 4- O -acetyl derivatives of the unsaturated and anhydro compounds are reported.

Synthesis and absolute configuration of two diastereoisomeric (1R,2S,3R)-and (1S,2S,3R)-2-amino-1-(2-furyl)-1,3-butandiols

Abstract The synthesis of (1 R , 2 S , 3 R ) and (1 S , 2 S , 3 R )-2-(N-benzoylamino)-1-(2-furyl)-1, 3-butandiols ( 15 ) and ( 16 ) from D-threonine is described. The assignment of absolute configuration of the newly formed asymmetric center at C-1 was based on the 1 H-NMR spectra of O-isopropylidene derivatives 17 and 18 .

Resolution of 4-cyano-4-(4-nitrophenyl)hexanoic acid: Synthesis of (R) and (S)-3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione (aminoglutethimide1)

Abstract Using (R)- or (S)-1-phenylethylamine as a resolving agent, (R)- and (S)-4-cyano-4-(4-nitrophenyl)hexanoic acids have been isolated. Cyclization of each enantiomer, followed by reduction of the nitro group, afforded (R)- and (S)-aminoglutethimide of high (>99% ee) enantiomeric purity, respectively. The absolute configuration of (R)-(+)-3-(4-nitrophenyl)-3-ethylpiperidine-2,6-dione was solved by X-ray single crystal analysis thus establishing the (R)-configuration of the dextrorotatory aminoglutethimide. Attempted resolution of the other precursor of aminoglutethimide, 4-cyano-2-ethyl-(4-nitrophenyl)butanoic acid with (S)-1-phenylethylamine led to the formation of the double salt. Its crystal structure was elucidated by X-ray crystallographic analysis.

Synthesis and absolute configuration of four diastereoisomeric 1-(2-furyl)-2-aminobutane-1,3-diols

Abstract The synthesis of N-benzenesulfonyl-N,O isopropylidene derivatives of (1R,2R,3S)-, (1S,2R,3S), (1R,2R,3R)- and (1S,2R,3R)-1-(2-furyl)-2-aminobutane-1,2-diols was accomplished by the addition of furyllithium to the similarly protected d -threoninal and d -allothreoninal, prepared in four steps from d -threonine and d -allothreonine, respectively. The configuration integrity of a β-hydroxy-α-amino aldehydes as well as the structure and the stereochemistry of resultant aminodiols derivatives was established by 1H NMR spectroscopy and single-crystal X-ray analysis.

A totally synthetic route to enantiomerically pure D and L-aminooctoses : stereocontrolled synthesis of methyl α-D-lincosaminide

Abstract A general method for the stereoselective synthesis of monosaccharides from furan compounds has provided a route to higher-carbon sugars with defined relative configuration of the side chain and the pyranose ring.2 For the synthesis of enantiomeritally pure 6-amino-6, 8-dideoxy-octoses, of which an antibiotic sugar lincosamine3 (1) is a notable representative, substituted furans of the type 2 with defined absolute configuration are required. Compounds 2 could be obtained by the addition of furan to the appropriate four-carbon chiral synthons,4 e.g., α-aminoaldehydes. Various N-protected α-aminoaldehydes prepared5 from natural amino acids are extensively used6 as chiral building blocks for the asymmetric synthesis of complex molecules. Recently, high diastereoselectivities have been reported for the reactions of N- or N,O-protected alaninals and serinals with different reagents,7 including 2-trimethylsilyloxyfuran8 and furyllithium.9 From these studies it appeared that the diastereoselectivity of t...

Total synthesis of protected form of fungi metabolite cortalcerone

Abstract Synthesis of methyl 4,5-dideoxy- -hex-4-enos-2-ulopyranosid-3-ulose ethylene acetal, derivative of first natural sugar with dihydropyranone moiety, from 5-acetoxymethylfurfural is described.

ADDITION OF ORGANOLITHIUM REAGENTS TO SOME CARBOHYDRATE ENONES

Abstract Addition of organolithium reagents to the sugar enones: alkyl 2,3,6-trideoxy-α- l - and 2,3-dideoxy-α- d -hex-2-enopyranosid-4-ulose has been examined. Butyl, benzyl and 2,5-dimethoxy-4-methylphenyllithium add, with increasing stereoselectivity, to the carbonyl group of the α,β-unsaturated ketosugars, whereas 2,5-dimethoxybenzyllithium undergoes stereospecific conjugate addition and 1,2-addition in the ratio of 1.7:1. The structure of the resultant carbinols is based on X-ray crystallographic evidence.

Synthesis of Enantiomerically Pure Anthracyclinones

The anthracycline antibiotics are among the most important clinical drugs used in the treatment ofhuman cancer. The search for new agents with improved therapeutic efficacy and reduced cardiotoxicity stimulatedconsiderable efforts in the synthesis of new analogues. Since the biological activity of anthracyclinesdepends on their natural absolute configuration, various strategies for the synthesis of enantiomericallypure anthracyclinones (aglycones) have been developed. They comprise: resolution of racemic intermediate,incorporation of a chiral fragment derived from natural and non-natural chiral pools, asymmetric synthesiswith the use of a chiral auxiliary or a chiral reagent, and enantioselective catalysis. Syntheticadvances towards enantiopure anthracyclinones reported over the last 17 years are reviewed.