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Biomedical subjects

D Horton

Publications and source records attributed to D Horton.

At least 73 records · Page 4Linked to original sources
PubMed1985

An unusual reaction of 1,6-anhydroaldohexopyranose derivatives leading to glycals.

Treatment of a solution of the 2-O-(N,N-dimethylsulfamoyl) derivative 3 of the levoglucosenone-derived carbocycle 1 in liquid ammonia at -40 to -50 degrees with sodium metal gave 73% of the glycal derivative 4 instead of the expected 2-deoxy derivative (2) of 1. Under the same conditions, the 2-O-(N,N-dimethylsulfamoyl) derivatives of 1,6-anhydro-3,4-dideoxy-4-C-methyl-beta-D-ribo- and -arabino-hexopyranoses gave, after acetylation, 70% of 6-O-acetyl-1,5-anhydro-2,3,4-trideoxy-4-C-methyl-D-erythro-hex-1-enit ol. In contrast, the 2-(N,N-dimethyl-sulfamates) obtained from 1,6-anhydro-3,4-O-isopropylidene-beta-D-galacto- and -talo-pyranose gave 6-O-acetyl-1,5-anhydro-2-deoxy-3,4-O-isopropylidene-D-lyxo-hex-1-enit ol in only low yields; the oxy substituent at C-3 may interfere with the reaction leading to the glycal.

Aldehydes↗
PubMed1985

Oxyhalogenation of glycals for the synthesis of anti-tumor-active 2'-halo daunorubicin analogs.

Alkoxyhalogenation of L-rhamnal diacetate with daunomycinone and N-iodosuccinimide afforded 37% of 7-O- (3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl)daunomycin one (4, NSC 331,962) and 7% of the beta-L-gluco analog (NSC 353,457); a similar procedure with L-fucal diacetate gave 77% of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-talopyranosyl) daunomycinone (NSC 327,472). Compound 4 showed high activity (T/C 247) and low toxicity in the P-388 lymphocytic leukemia screen in mice.

Antineoplastic Agents↗
PubMed1984

Crystalline 2,3:4,5-di-O-isopropylidene-DL-arabinose diethyl dithioacetal: some reactions of acetal derivatives of arabinose.

Acetonation of the diethyl dithioacetals of D- and L-arabinose gives the corresponding 2,3:4,5-diisopropylidene acetals (2a and 2b) as oils having [alpha]D +82 and -81 degrees, respectively; in admixture, the enantiomers form a well crystallized racemate, m.p. 43-45 degrees. The initial product of acetonation is the 4,5-monoisopropylidene acetal. Demercaptalation of 2a with mercury(II) chloride-cadmium carbonate gives 2,3:4,5-di-O-isopropylidene-aldehydo-D-arabinose (5) in high yield, but the literature procedure employing mercury(II) chloride-mercury(II) oxide affords a mixture of 5 and 1,2:3,4-di-O-isopropylidene-beta-D-arabinopyranose (6). A trace of acid readily and completely converts the aldehydo derivative 5 into the cyclic diacetal 6.

Acetals↗
PubMed1984

3'-Deamino-4'-epi-3'-hydroxy-daunorubicin and -doxorubicin. Synthesis and antitumor activity.

3'-Deamino-4'-epi-3'-hydroxy-daunorubicin (11) and -doxorubicin (14) have been synthesized. In the in vivo murine P-388 lymphocytic leukemia assay, these two compounds were more active than daunorubicin (1) and doxorubicin (2), respectively. Comparative studies in the P-388 assay indicated 3'-deamino-3'-hydroxydoxorubicin (3) to be more active than its 4'-epimer 14.

Animals↗
PubMed1984

Synthesis and antitumor activity of 3'-deamino-3'-hydroxydoxorubicin. A facile procedure for the preparation of doxorubicin analogs.

Two successful routes have been developed for preparation of 3'-deamino-3'-hydroxydoxorubicin (11), based on protection of the 14-hydroxyl group of the aglycon by using tert-butylchlorodimethylsilane. The key intermediate, 14-O-tert-butyldimethylsilyl-7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-ly xo -hexopyranosyl)adriamycinone (9), was successively deacetylated and desilylated in high yield to give the desired product 11. This route constitutes a general method of access to glycon-modified doxorubicin analogs. Compound 11 showed high antitumor activity in vivo in the murine P388 lymphocytic leukemia assay.

Animals↗
PubMed1983

Chiral synthesis of asymmetrically tetra-C-substituted cyclopentane derivatives by Diels-Alder addition of cyclopentadiene to unsaturated acyclic-sugar derivatives.

Optically pure, substituted cyclopentane derivatives of interest in synthesis of prostaglandin analogs have been obtained by stereocontrolled addition of cyclopentadiene to trans alpha,beta-unsaturated sugar derivatives. Methyl (E)-4,5,6,7-tetra-O-acetyl-2,3-dideoxy-D-arabino-hept-2-enonate (2), obtained by Wittig addition of Ph3PCHCO2Me to aldehydo-D-arabinose tetraacetate, reacted with cyclopentadiene in boiling toluene to give 40% of a crystalline, norbornene adduct (3) having the 5S-exo ester, 6S-endo sugar-chain configuration, as established by crystallography and by conversions into the known, crystalline (2S,3S)-bis(p-tolylsulfonyloxymethyl)bicyclo[2.2.1]heptane. Likewise, the L enantiomer (19) of 2 was converted into the crystalline enantiomer of 3; chromatographic resolution of the other Diels-Alder adducts from the reaction afforded lesser amounts of the other three possible isomeric adducts, which were characterized by appropriate conversions. The Ph3PCHCO2Me Wittig adduct (9) from 2,3:4,5-di-O-isopropylidene-aldehydo-D-arabinose with cyclopentadiene in hot toluene gave a crystalline mixture of the isomeric 5S,6S adducts (10 and 11), separable after deacetonation and acetylation as the already characterized product 3 and its 6S-endo ester, 5S-exo sugar-chain isomer. Likewise, the L enantiomer of the D dienophile 9 gave a crystalline mixture of 5R,6R adducts that were the enantiomers of 10 and 11. A reversed ratio of adducts resulted when the tetraacetylated L dienophile 19 reacted at 0 degrees with cyclopentadiene under AlCl3 catalysis, and 36% of the crystalline 5S-endo ester, 6S-exo sugar-chain adduct (23) was obtained. Hydroxylation-glycol cleavage of the double bond in 23, followed by reduction and acetylation, gave 65% of an optically pure cyclopentane derivative having five chiral centers of the same absolute configuration as in prostaglandin F1 alpha.

Carbohydrates↗
PubMed1983

Ergonomics approach applied to the problems of two disabled people.

Two case studies are presented to illustrate the potential of an ergonomics approach, in facilitating and widening the range of activities disabled people can perform. This approach, as illustrated here, can be used as an essential practical tool in employment rehabilitation centres and the resettlement of disabled people in open employment.

Journal Article↗
PubMed1983

14-esters of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl)adriamycinone: synthesis and antitumor activity.

A range of 14-esters (8 approximately 13) of the title compound, 3'-deamino-3'-hydroxydoxorubicin 3',4'-diacetate (5), has been synthesized by nucleophilic substitution of the corresponding 14-bromide (6) by the appropriate sodium carboxylate salts. Antitumor activities were determined in vivo in the murine P388 lymphocytic leukemia assay and compared with those of the 14-hydroxy and 14-acetoxy analogs.

Animals↗
PubMed1981

Synthesis and antitumor activity of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl)adriamycinone.

The title compound (7), the 3'-acetoxy-4'-O-acetyl analog of adriamycin (doxorubicin), was synthesized in approximately 50% net yield from daunomycinone by bromination at C-14, glycosylation of the product at O-7 with 3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl chloride, and replacement of the 14-bromo substituent by a hydroxyl group; other possible routes to 7 gave lower yields. The product 7, a non-aminated analog of the anthracycline antibiotics, showed high antitumor activity coupled with low acute toxicity in a broad range of tests in mice.

Animals↗
PubMed1981

31P nuclear magnetic resonance spectroscopy of lipopolysaccharides from Pseudomonas aeruginosa.

Intact lipopolysaccharide antigens isolated from seven different immunotypes of Pseudomonas aeruginosa have been examined by 31P-NMR spectroscopy. These macromolecular complexes contain phosphorus covalently attached to the carbohydrate residues present in the lipid A moiety and the 'core' oligosaccharide region. The spectral signals for various ortho- and pyrophosphoric esters were observed. All phosphate groups appeared to be monoesterified. Certain shifts characteristic for phosphate diester groups, observed in lipopolysaccharide complexes from other Gram-negative bacteria, were absent. Furthermore, no evidence was found to indicate that phosphate groups are involved in the covalent linkage of individual lipopolysaccharide complexes to form dimers or trimers.

Diphosphates↗
PubMed1981

New adriamycin analogs. Synthesis and antitumor activity of 14-substituted 7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl)daunomycinones.

The 14-azido-, 14-thiocyanato-, 14-acetoxy-, and 14-acetylthio- derivatives of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl)daunomycinone were synthesized by displacement reactions conducted on the corresponding 14-bromide. The in vivo antitumor activities of the products were compared with that of the 14-hydroxyl derivative in the murine P-388 lymphocytic leukemia assay. The 14-acetoxy derivative was highly active and of low toxicity; the other products showed negligible or low activities.

Animals↗
PubMed1979

Synthesis and antitumor activity of sugar-ring hydroxyl analogues of daunorubicin.

Daunorubicin analogues in which the natural amino sugar, daunosamine, is replaced by neutral 2,6-dideoxy-hexopyranosyl residues have been prepared in high yields. Glycosidation of 3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl chloride (13) with daunomycinone under Koenigs-Knorr conditions yielded exclusively the protected alpha-anomeric product 4, which was converted into the free glycoside 5. In contrast, the 1-chloro-D-ribo isomer 19, bearing p-nitrobenzoyl groups for hydroxyl-group protection, furnished a 5:3 mixture of the alpha (6) and beta (7) glycosides. Separation and individual deprotection afforded the target compounds 8 (from 6) and 9 (from 7). Whereas all of the D-ribo analogues (6--9) are inactive as antitumor agents in vivo against P388 lymphocytic leukemia in mice, the protected L-lyxo glycoside 4 (T/C 186) and also the free glycoside 5 (T/C 183) are highly effective in this test system; 5 is also active (T/C 146) in vivo against murine B16 melanocarcinoma.

Animals↗