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Signaling of all-trans retinoic acid (ATRA) through nuclear retinoid acid (RA) receptors regulates several biological functions in airway epithelial cells, eosinophils, and immune cells, yet its impact on different in vivo aspects of pulmonary allergic reaction remains elusive. We compared the effect of a treatment with liposomally encapsulated ATRA (Lipo-ATRA) in a mouse model of ovalbumin (OVA)-induced T helper (Th) 2-type responses and airway remodeling. Daily intraperitoneal injections of 10 mg/kg Lipo-ATRA, at the time of each of the 2 systemic sensitizing injections, increased OVA-induced Immunoglobulin E synthesis, bronchoalveolar lavage (BAL) eosinophilia, and accumulation of IL-5, transforming-growth factor b1, fibronectin, eotaxin/chemokine (C-C motif) ligand 11 (eotaxin/CCL11) and regulated upon activation, normal T expressed and secreted chemokine (C-C motif) ligand 5. In contrast, Lipo-ATRA, administered during each of the 4 intranasal OVA challenges, did not affect these variables. Regardless of the treatment regimen, Lipo-ATRA augmented mucin levels in BAL fluid and reduced lung total collagen content. In vitro incubation of mouse splenocytes or purified spleen cluster of differentiation (CD) 4-positive T lymphocytes, with ATRA, increased, respectively, OVA- and anti-CD 3 antibody-induced IL-4 and IL-5 production and inhibited IFNg release. These findings demonstrate that, when given during systemic sensitization, Lipo-ATRA exacerbates allergic immune and inflammatory responses, most likely by promoting Th2 development. J. Nutr. 137: 2730‐2736, 2007.

A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5′-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides...

Condensation of 4-benzyloxy-3-methoxyanthranilic acid ( 3 ) with 5-iodo-1,2,3,4-tetramethoxybenzene ( 4 ) gave 6-benzyloxy-1,2,3,4,5-pentamethoxy-9-acridone ( 5 ), which was then converted into glyfoline ( 1 ) via N-methylation, selective de-O-methylation, and debenzylation. The synthetic glyfoline ( 1 ) is identical with an authentic sample isolated from plant.

Condensation of 4-benzyloxy-3-methoxyanthranilic acid ( 3 ) with 5-iodo-1,2,3,4-tetramethoxybenzene ( 4 ) gave 6-benzyloxy-1,2,3,4,5-pentamethoxy-9-acridone ( 5 ), which was then converted into glyfoline ( 1 ) via N-methylation, selective de-O-methylation, and debenzylation. The synthetic glyfoline ( 1 ) is identical with an authentic sample isolated from plant.

Methylated or acetylated heptopyranose derivatives were prepared variously from l - glycero - d - manno - and d - glycero - d - manno -heptopyranose, O - l - glycero - a - d - manno -heptopyranosyl-(1 → 3)- l - glycero - d - manno -heptopyranose, O - l - glycero - a - d - manno -heptopyranosyl-(1 → 7)- l - glycero - d - manno -heptopyranose, and O - l - glycero - a - d - manno -heptopyranosyl-(1 → 7)- O - l - glycero - a - d - manno -heptopyranosyl-(1 → 3)- l - glycero - d - manno -heptopyranose, which are structural elements of the heptose region of enterobacterial lipopolysaccharides. Each derivative was investigated by g.l.c. and g.l.c.-m.s., and the retention times and fragmentation patterns were used to identify partial structures of the heptose region of the core oligosaccharide of bacterial LPS.

Three methods for the synthesis of the title compounds starting from benzyl 2,3,4-tri-O-benzyl-α- d -manno-hexodialdo-1,5-pyranoside (7 have been elaborated. Conversion of 7 into the cyanohydrin followed by reduction to give the amine and then deamination gave a derivative of l -glycero- d -manno-heptose in low yield. Condensation of 7 with 2-methylfuran gave two stereoisomeric 6-C-(2-methyl-5-furyl) derivatives. The preponderant stereoisomer was ozonised and then reduced to give a derivative of d -glycero- d -manno-heptose. Condensation of 7 with allyloxymethylmagnesium chloride gave derivatives of both heptoses in good yield and with an l -glycero d -glycero ratio of 3.2:1. Deprotection of these derivatives gave the heptoses in high yield.

Disaccharides linked α (1–3) and α (1–7) and a trisaccharide linked α (1–7) and α (1–3) have been synthesized from suitably blocked L-glycero-D-mannoheptose derivatives using the trichloroacetimidate approach.

Three methods for the synthesis of the title compounds starting from benzyl 2,3,4-tri-O-benzyl-α- d -manno-hexodialdo-1,5-pyranoside (7 have been elaborated. Conversion of 7 into the cyanohydrin followed by reduction to give the amine and then deamination gave a derivative of l -glycero- d -manno-heptose in low yield. Condensation of 7 with 2-methylfuran gave two stereoisomeric 6-C-(2-methyl-5-furyl) derivatives. The preponderant stereoisomer was ozonised and then reduced to give a derivative of d -glycero- d -manno-heptose. Condensation of 7 with allyloxymethylmagnesium chloride gave derivatives of both heptoses in good yield and with an l -glycero d -glycero ratio of 3.2:1. Deprotection of these derivatives gave the heptoses in high yield.

Disaccharides linked α (1–3) and α (1–7) and a trisaccharide linked α (1–7) and α (1–3) have been synthesized from suitably blocked L-glycero-D-mannoheptose derivatives using the trichloroacetimidate approach.