Synthesis of dl-3-Hydroxydihydro-β-damascone and Dihydro-β-damascone

The Rupe rearrangement of the appropriate acetylenic alcohols afforded dihydro-β-damascone (XII) and its 3-hydroxy derivative (I). The latter is an aroma component of Manila leaf tobacco.     

Allelopathy of the moss Rhynchostegium pallidifolium and 3-hydroxy-β-ionone

The moss Rhynchostegium pallidifolium (Mitt.) A. Jaeger, which often forms large pure colonies on soils and rocks, inhibited the hypocotyls and root growth of cress (Lepidium sativum L.) seedlings when R. pallidifolium and cress were incubated together on agar medium. The inhibition of cress was greater at the close position from the moss than at the far position from the moss. 3-Hydroxy-β-ionone was found in the medium and concentration of 3-hydroxy-β-ionone in the medium was greater at the close position than at the far position from R. pallidifolium, suggesting that R. pallidifolium may secrete 3-hydroxy-β-ionone into the medium. Exogenously applied 3-hydroxy-β-ionone inhibited the growth of hypocotyls and roots of cress at concentrations greater than 1 and 3 µM, respectively. Considering the growth inhibitory activity and concentrations found in the medium, 3-hydroxy-β-ionone was estimated to be able to cause 46–64% of the observed growth inhibition of cress hypocotyls and roots by R. pallidifolium. Therefore, 3-hydroxy-β-ionone may play an important role in the allelopathic activity of R. pallidifolium and may help competition with neighboring plants resulting in the formation of pure colonies.Key words: allelopathy, growth inhibitor, 3-hydroxy-β-ionone, phytotoxicity, Rhynchostegium pallidifoliumBryophytes are almost free from attack by micro-organism and insects, and their herbarium specimens usually do not need special treatment against insects and micro-organism. In addition, many bryophyte species have their own particular odors and tastes.¹ These bryophyte characteristics are probably attributed to chemical constituents inherent in their structures. In fact, many biologically active substances, such as phenolics and terpenoides, have been isolated from bryophytes.^2–5Several higher plants can not grow well in places where some bryophytes occurred. Some bryophytes dominate plant communities and form large pure colonies on soils and rocks on sunny places of lowland to upland areas including marshy places.^1,6,7 Therefore, allelopathic chemical interactions may play an important role in the domination of bryophytes in these plant communities. In contrast to higher plants, however, there only was a preliminary study on allelopathy of bryophytes. The moss Rhynchostegium pallidifolium (Mitt.) A. Jaeger, which belongs to Brachytheciaceae family of Bryopsida (moss) class, Bryophyta division, also forms large pure colonies and possesses strong allelopathic activity. An allelopathic substance of the moss was recently isolated and identified as 3-hydroxy-β-ionone.⁸     

Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes

A series of 3-arylnortrop-2-enes and 3α-arylmethoxy-3β-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (K_i = 0.3 nM). The 3α-arylmethoxy-3β-arylnortropanes were generally SERT selective with the 3α-(3.4-dichlorophenylmethoxy)-3βphenylnortrop-2-ene (7c) possessing subnanomolar potency (K_i = 0.061 nM). However, 3α-(3,4-dichlorophenylmethoxy)-3β-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT K_i = 22 nM), (SERT K_i = 6 nM) and (NET K_i = 101 nM)].     

Novel Synthesis of 3-Hydroxy-β-damascone, 3-Hydroxydihydro-β-damascone and β-damascenone

Naturally occurring damascone analogues, 3-hydroxy-β-damascone, 3-hydroxydihydro-β-damascone and β-damascenone, which are known as key substances for the flavor of rose oil and tobacco, were synthesized via Diels-Alder reaction of the reactive diene, l-methoxy-3-trimethylsilyloxy-butadiene.     

Isolation of R-(−)-3-Hydroxy-β-ionone from Burley Tobacco

The tritium-hydrogen exchange method was used to determine the total racemization of amino acid residues of four proteins (ribonuclease A, lysozyme, soybean protein and casein) during their exposure to an alkali. Tritium was incorporated with first order kinetics into these proteins during their incubation in 0.2 n NaOH at 40°C. The tritium-hydrogen exchange increased as the temperature and the alkali concentration increased. In contrast, pepsin digestibility decreased extensively in the initial stage of the treatment. This phenomenon was verified by the subsite theory of protease, that only minor racemization renders the extended range of the peptide chain around the racemized amino acids non-susceptible to pepsin. General precautions against the racemization of food protein treated with alkalis are discussed briefly in terms of the deterioration of nutrients.     

Synthesis of Derivatives of 3-Methylxantheve and 1-Methyl-3-Isobutylxanthine 7-β-D-Ribofuranosides

Abstract

Methods of synthesis of 7–(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)-8-chloro-3-methylxanthine (5a) and l-methyl-3-isobutylxanthine (5b) were reported. Further nucleophilic displacement of chlorine has provided the corresponding 8-alkylamino and 8-benzylamino derivatives (6a,b-9a,b). Several 5′-acyl analogues of 3-methylxanthine-7–β-D-ribofuranoside (15–18) were synthesized using 7–(2′,3′-di-O-isopropylidene-β-D-ribofuranosyl)-3-methylxanthine (10) as intermediate.     

Synthesis of β-ionone derived chalcones as potent antimicrobial agents

A series of chalcones (3a–v) have been synthesized by condensation of β-ionone (1) with a variety of aldehydes (2a–v). The synthesized compounds have been screened for their in vitro antimicrobial activity against five bacterial and five fungal strains, using disc diffusion assay. The evaluated compounds display a wide range of activities, from completely inactive to the highly active compounds. Some of the compounds are also active against methicillin resistant staphylococcus aureus (MRSA).     

Synthesis and cytotoxic analysis of some disodium 3β,6β-dihydroxysterol disulfates

Disodium 3β,6β-dihydroxy-5α-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH₄ in the presence of NiCl₂ to produce cholest-3β,6β-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3β,6β-dihydroxy-5α-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na⁺) yielded the target steroid 1. Disodium 24-ethyl-3β,6β-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3β,6β-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity.     

Synthesis of 14β-cholesta-5,7-dien-3β-ol

5, 7-Cholestadien-3β-ol was transformed into 14β-cholesta-5, 7-dien- 3β-ol in six steps. The inversion of the stereochemistry at C-14 was obtained by a selective protection of the Δ⁵ and the elaboration of the Δ⁷ double bond.     

Chemo-enzymatic Synthesis of 3-Deoxy-β-D-ribofuranosyl Purines and Study of Their Biological Properties

Abstract

9-(3-Deoxy-β-d-erythro-pentofuranosyl)-2,6-diaminopurine (2) was synthesized by an enzymatic transglycosylation of 2,6-diaminopurine using 3′-deoxycytidine (1) as a donor of the sugar moiety. Nucleoside 2 was transformed to 3′-deoxy guanosine (3), 9-(3-deoxy-β-d-erythro-pentofuranosyl)-2-amino-6-oxopurine (3′-deoxyisoguanosine; 4), and 9-(3-deoxy-β-d-erythro-pentofuranosyl)-2-fluoroadenine (5). Compounds 2–5 were evaluated for their anti-HIV activity.     

Synthesis and Properties of Phosphorylated 3′-O-β-D-Ribofuranosyl-2′-deoxythymidine

Abstract

A strategy was developed for the synthesis of 3′-O-β-D-ribofuranosyl 2′-deoxythymidine derivatives using three different protecting groups, which allows the synthesis of a phosphoramidite building block for oligonucleotide synthesis. Likewise the 5′-O- and 5″-O-phosphorylated analogues were synthesized and their conformation was determined using NMR spectroscopy.     

Synthesis and evaluation of bivalent, peptidomimetic antagonists of the αvβ3 integrins

Targeting the integrin α(v)β(3) by directly interfering with its function is considered to be an effective and non-cytotoxic strategy for the treatment of tumor. In this study, a series of bivalent analogs of peptidomimetic integrin antagonists IA 1 and IAC 2 were designed, synthesized, and evaluated for their ability to inhibit the integrin α(v)β(3). All the bivalent ligands exhibited increased potency compared to that of their monomeric counterparts for the integrin α(v)β(3) with low nanomolar range binding affinity. The best bivalent ligand 6 tested in the series has an IC(50)=0.09 nM evaluated by ELISA assay. We conclude that multivalency is providing a useful template for the development novel integrin α(v)β(3) antagonists as potential therapeutics.     

Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β

The synthesis, GSK-3β inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors.     

Synthesis and Antiviral Evaluation of N-β-D-Ribosides of Ergot Alkaloids

Abstract

N-β-D-Ribosides of agroclavine (1), elymoclavine (2), lysergene (4), lysergol (3), and 9, 10-dihydrolysergol (5) were prepared by SnCl₄ catalyzed ribosylation of their TMS derivatives with 1-O-acetyl-2, 3,5-tri-O-benzoyl-β-D-ribofuranose. None of the new compounds exhibited activity against HIV or other viruses tested.     

Synthesis and initial evaluation of novel,non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5

The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the α_v-integrins α_vβ₃ and α_vβ₅ is described. High-throughput screening of an extensive series of ECLiPS? compound libraries led to the identification of compound 1 as a dual inhibitor of the α_v-integrins α_vβ₃ and α_vβ₅. Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the α_vβ₃ and α_vβ₅ integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile.     

Synthesis of α- and γ-l-Glutamyl Dipeptides of l-β-Phenyl-β-Alanine

α- and γ-l-Glutamyl dipeptides of l-β-phenyl-β-alanine are synthesized for the first time from l-glutamic acid and l-β-phenyl-β-alanine. In addition, the preparations and the properties of new intermediates, that is, l-β-phenyl-β-alanine benzylester p-toluenesulfonate and the N-carbobenzyloxy-α- and γ-dipeptide benzylesters, are described. Further proof of the structure previously proposed for the naturally occurring peptide is obtained by a critical comparison of the isolated and synthetic materials by various physical and chemical methods.     

Synthesis of 4-hydroxy-β3-homoprolines and their insertion in α/β/α-tripeptides

The stereoselective syntheses of 2-cyclopropyl- and (2S)-2-hydroxymethyl-(3R,4S)-4-hydroxy-β³-homoproline are described. The reported amino acids were constructed through 1,3-dipolar cycloaddition of strained alkylidenecyclopropanes with enantiopure pyrroline N-oxides derived from malic acid followed by thermal rearrangement of the adducts in the presence of trifluoroacetic acid. The two-step sequence afforded the homoprolines suitably protected to be directly used as building blocks in peptidomimetic synthesis as proved by the synthesis of the two model mixed α/β/α tripeptides Phe-β³-HPro-Val.     

Synthesis and X-Ray Crystal Structure of 2-β-D-Ribofuranosylthiazole-4-Carboxamide-N3-Oxide

Abstract

2-β-D-Ribofuranosylthiazole-4-carboxamide-N₃-oxide (3) has been prepared by oxidation of tiazofurin (2) with hydrogen peroxide in the presence of trifluoroacetic acid. The absolute structure of 3 has been determined by X-ray diffraction techniques employing Mo Kα radiation. The thiazole ring in 3 is planar and the glycon moiety is in the ³E configuration. The N3-C4 bond in 3 is significantly larger (1.412 Å) than that found in tiazofurin (1.376 Å). Similar to tiazofurin, the S…04’ intramolecular contact distance is considerably shorter than the sum of the van der Waals radii, which favors the anti conformation of 3.