Syntheses related to the carbohydrate moiety in lincomycin

Howarth, G. B.; Lance, D. G.; Szarek, Walter A.; Jones, J. K. N.

doi:10.1139/v69-009

Cited by 65 publications

(14 citation statements)

References 7 publications

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“…Chemical synthesis of 8-carbon sugar derivatives as potential intermediates leading to the production of methyl 6-amino-6,8-dideoxy-1-thi-D-erythro-␣-D-galacto-octopyranoside, the carbohydrate moiety of lincomycin, appears to require an isomerization step (51).…”

Section: Resultsmentioning

confidence: 99%

Biosynthesis of Inner Core Lipopolysaccharide in Enteric Bacteria Identification and Characterization of a Conserved Phosphoheptose Isomerase

Brooke¹,

Valvano

1996

Journal of Biological Chemistry

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The lpcA locus has been identified in Escherichia coli K12 novobiocin-supersensitive mutants that produce a short lipopolysaccharide (LPS) core which lacks glyceromannoheptose and terminal hexoses. We have characterized lpcA as a single gene mapping around 5.3 min (246 kilobases) on the E. coli K12 chromosome and encoding a 22.6-kDa cytosolic protein. Recombinant plasmids containing only lpcA restored a complete core LPS in the E. coli strain 711. We show that this strain has an IS5-mediated chromosomal deletion of 35 kilobases that eliminates lpcA. The LpcA protein showed discrete similarities with a family of aldose/ketose isomerases and other proteins of unknown function. The isomerization of sedoheptulose 7-phosphate, into a phosphosugar presumed to be D-glycero-D-mannoheptose 7-phosphate, was detected in enzyme reactions with cell extracts of E. coli lpcA ؉ and of lpcA mutants containing the recombinant lpcA gene. We concluded that LpcA is the phosphoheptose isomerase used in the first step of glyceromannoheptose synthesis. We also demonstrated that lpcA is conserved among enteric bacteria, all of which contain glyceromannoheptose in the inner core LPS, indicating that LpcA is an essential component in a conserved biosynthetic pathway of inner core LPS.

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Section: Resultsmentioning

confidence: 99%

Biosynthesis of Inner Core Lipopolysaccharide in Enteric Bacteria Identification and Characterization of a Conserved Phosphoheptose Isomerase

Brooke¹,

Valvano

1996

Journal of Biological Chemistry

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“…Reaction of 15 with freshly prepared diethylaminosulfur trifluoride under the mild conditions reported for the conversion of aldehyde or ketone carbonyl groups to the corresponding geminal difluorideZ1 provided 6-deoxy-6,6-difluoro-1,2:3,4-diisopropylidene-a-~-galactopyranose (20) in good yield.22 Deprotection of 20 with aqueous trifluoroacetic acid gave the desired 6-deoxy-6,6-difluoro-L-galactopyranose (21) as a crystalline solid. Acetylation of 21 produced a mixture of peracetylated products; separation of this mixture by column chromatography provided crystalline 6-deoxy-6,6-difluoro-1,2,-3,4-tetra-O-acetyl-a-~-galactopyranose (22a) and an inseparable mixture consisting of 6-deoxy-6,6-difluoro-1,2,3,4-tetra-O-acetyl-@-~-galactopyranose (22b), 6-deoxy-6,6-difluoro-l,2,3,5-tetra-0-acetyl-a-~-galactofuranose (23a), and 6-deoxy-6,6-difluoro-1,2,3,5-tetra-Oacetyl-0-L-galactofuranose (23b).…”

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confidence: 99%

Synthesis and biological activity of potential antimetabolites of L-fucose

May¹,

Sartorelli²

1979

J. Med. Chem.

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6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo derivatives; since these compounds were all capable of alkylation, it is conceivable that their cytotoxic action is a consequence of this property. In agreement with this interpretation, none of the agents synthesized showed specific inhibition of the incorporation of L-[3H]fucose into glycoprotein.

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“…Catalytic osmylation l 6 of the (E)-octenopyranose (6) produced a mixture containing 1,2 : 3,4-di-O-isopropylidene-p-L-threo-D-gafacro-octopyranose * (12) and the a-D-fhreo-Dgafacto isomer (13) in the ratio 7: 1. In this and all subsequent oxidations, the ratios of the products were determined by integration over the resonances for the anomeric protons in the 'H n.m.r.…”

Section: Resultsmentioning

confidence: 99%

Higher-carbon sugars. Part 1. The synthesis of some octose sugars via the osmylation of unsaturated precursors

Brimacombe¹,

HANNA²,

Kabir³

et al. 1986

J. Chem. Soc., Perkin Trans. 1

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The stereochemical outcome of the osmium tetraoxide oxidation of a number of unsaturated carbohydrate derivatives, including (€) -and (Z) -6,7-dideoxy-l,2 : 3,4-di-~-isopropylidene-a-o-ga/acto-oct-6-enopyranose (6) and (9), methyl (Z) -6,7 -dideoxy-1,2 : 3,4-di -0-isopropylidene-a-D-galacto-oct -6-enopyranuronate ( 8 ) , and 7,8-dideoxy-1,2 : 3,4-di-0-isopropylidene-a-D-glycero-~-ga/acto-oct-7 -enopyranose (1 0), has been examined. Such oxidations resulted in the preparation of the synthetically usef u I octose derivatives 1,2 : 3,4-d i -0 -isopropy l idene-x -D -erythro -D -ga/acto -octopyranose (1 8) and 1,2: 3,4: 6,7-tr~-~-~sopropyl~dene-~-~-erythro-~-ga/acto-octopyranose (31 ), as well as syntheses of Lthreo-D -ga/acto-octitol (1 4), D-erythro -D-ga/acto-octitol (21 ), L-erythro-o-galacto-octitoi (29), and D -threo -D-ga/aCtO-OCtitOI (35).The synthesis of sugars with carbon chains composed of more than six carbon atoms, the so-called higher-carbon sugars,' poses an interesting challenge.'-4 Such syntheses require the formation of carbon-carbon bonds and control of the stereochemistry at each newly created stereocentre. The concept of asymmetric synthesis was first realised with the Kiliani-Fischer cyanohydrin reaction, which was used to extend the aldose chain by one carbon atom from the reducing end.2*3 This procedure has been applied to most h e x o s e~,~.~ but, because of the asymmetric nature of the cyanohydrin synthesis, only a limited number of heptoses are available as substrates. In certain cases, syntheses were extended to give octose, nonose, and decose sugars, but the structures of many of these highercarbon sugars remain unproved.' In recent times, the cyanohydrin procedure has been augmented by other methods; ' theseO+ permit extension of the sugar chain by two or more carbon atoms in a single step, but seldom in a wholly predictable way, so that in spite of the long standing interest in higher-carbon sugars, only a handful of them containing eight or more carbon atoms are known.2 A resurgence of interest in the synthesis of higher-carbon sugars has followed the discovery of important antibiotics containing such higher-carbon sugars as the amino-octodioses (1) (from apramycin and oxyapramycin ') and the undecose hikosamine 8*9 (2) (from hikizimycin 9). Our interest in the synthesis of these and other higher-carbon sugars of biological interest prompted an examination of the oxidation of various unsaturated sugar derivatives with osmium tetraoxide. In choosing this approach we were influenced by the knowledge that the osmylation of allylic alcohols and ethers proceeds with moderate to marked stereoselectivity, which can be predicted on an empirical basis. l o Initially our efforts were directed towards the synthesis of octose sugars by extending the chain of the hexodialdose" (3) by two carbon atoms, as outlined in the Scheme. Unlike traditional methods, the carbon chain of the original hexose, in this instance D-galactose, is undergoing extension from the non-reducing end. This particular system...

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Syntheses related to the carbohydrate moiety in lincomycin

Cited by 65 publications

References 7 publications

Biosynthesis of Inner Core Lipopolysaccharide in Enteric Bacteria Identification and Characterization of a Conserved Phosphoheptose Isomerase

Biosynthesis of Inner Core Lipopolysaccharide in Enteric Bacteria Identification and Characterization of a Conserved Phosphoheptose Isomerase

Synthesis and biological activity of potential antimetabolites of L-fucose

Higher-carbon sugars. Part 1. The synthesis of some octose sugars via the osmylation of unsaturated precursors

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