Allylic Sulfones Containing Triene Moieties as Key Synthons for Carotenoid Synthesis

An efficient synthetic method for the allylic sulfone 2 containing a conjugated triene moiety has been proposed involving i) coupling of allylic sulfones 4 with the C₅ bromoallylic sulfide 5 , ii) base‐promoted dehydrosulfonation in the presence of allylic sulfide, and iii) selective oxidation of the resulting trienyl sulfide to the corresponding sulfone. Total synthesis of lycopene starting from the C₁₅ allylic sulfone 2b has been described, where the new C₁₀ bis(chloroallylic) sulfone 11 proved to be a useful substitute for the C₁₀ bis(chloroallylic) sulfide 3 , which did not require the problematic chemoselective sulfur oxidation in a conjugated polyene.     

1-Phenyl-2-thiocyanatoethanone as Synthons in Heterocyclic Synthesis

This review presents a systematic and comprehensive survey of the method of preparation and the chemical reactivity of 1-phenyl-2-thiocyanatoethanone. The target compound is an important intermediate for the synthesis of a variety of synthetically useful and novel heterocyclic systems.     

Iterative Synthesis of Nucleoside Oligophosphates with Phosphoramidites

P‐Amidites can be used in iterative couplings to selectively give mixed P^III–P^V anhydrides. These intermediates can be oxidized followed by a rapid removal of the two terminal fluorenylmethyl groups. An iterative synthesis (coupling, oxidation, deprotection) of nucleoside oligophosphates can be carried out in solution and on a solid support. The coupling rates and yields are high, the procedures convenient (non‐dry reagents and solvents, ambient conditions, unprotected nucleotides), and the purification is very simple. The method works with all canonical nucleosides and holds promise for significant simplification of the usually cumbersome process of P‐anhydride bond construction.     

Individual Isomers of Dinucleoside Boranophosphates as Synthons for Incorporation into Oligonucleotides: Synthesis and Configurational Assignment

Individual isomers of the protected boranophosphates 5a and 5b , i.e., the N⁶‐benzyl‐2′‐deoxy‐5′‐O‐(4,4′‐dimethoxytrityl)adenosin‐3′‐yl 2′‐deoxy‐4‐O‐(4‐nitrophenyl)uridin‐5′‐yl boranophosphates, were synthesized via stereospecific silylation and boronation of their H‐phosphonate precursors. 2D‐NMR Spectroscopic studies yielded an initial assignment of the isomer configuration, which was further confirmed unambiguously by a parallel chemical synthesis. Deprotection of the `dimers' 5a and 5b yielded the individual [P(R)]‐ and [P(S)]‐isomers 7a and 7b , respectively, i.e., the 2′‐deoxyadenosin‐3′‐yl 2′‐deoxycytidin‐5′‐yl boranophosphates. Their substrate properties toward phosphodiesterase I were identical to those of the previously characterized isomers of dithymidine boranophosphate. The protected `dimers' 5a and 5b can be used as synthons to incorporate the boranophosphate linkage with a defined configuration to selected positions of an oligonucleotide chain.     

4,4-Dialkoxybutan-2-ones as Synthons

The review considers the synthetic potential of 4,4-alkoxybutan-2-ones which are promising synthons available from diacetylene-containing industrial gases. The reactivity of 4,4-dialkoxybutan-2-ones toward mono- and difunctional reagents, as well as in cycloaddition processes, is discussed.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 9–32.Original Russian Text Copyright © 2005 by Maretina.     

Clay Catalysis: Synthesis of Organosulphur Synthons

Abstract

The Montmorillonite KSF catalyses the synthesis of a large variety of organic sulphur compounds from carbonyl compounds: dithianes, thioacetals, thioketals, thiochromanes.

Clay minerals are known to cataiyse a variety of organic reactions(1). In these reaction, the clay catalyst acts as a solid Bronsted acid. One of the most acidic, Montmorillonite manufactured by Sud Chemie, is the KSF catalyst. Clay is inexpensive and offers several advantages to the classic acid: a strong acidity (Ho = ?8 to ?9), no corrosive action, selectivity and easy work-up.

We report here, that KSF clay is a convenient catalyst for the synthesis of useful thio-organic reagents : dithianes, thioketals, trithioorthoformiates, thiochromanes. The condensations of the thiol with the carbonyl compounds were completed in refluxing toluene in presence of KSF with the azeotropic separation of water. Generally the pure compound was obtained in these reactions and the work-up very simple.     

Copper-Catalyzed Enantioselective Synthesis of α-Hydroxyamine Using Monodentate Phosphoramidites

Development of new methods for the introduction of a nitrogen atom to a carbonyl group is still the most important synthetic target. Cu-catalyzed addition of organozinc reagents to α,β-unsaturated carbonyl compounds has been the subject of intensive investigation.[1] Moreover, trapping of the intermediate Zn-enolates has been achieved using nitrosobenzene. To demonstrate the feasibility of developing enantioselective variants of these tandem C-C bond formations,α,β-unsaturated substrates a～d was subjected to standard reaction conditions using Feringa's (L1*, L2*) and our own phosphoramidite ligands (L3*, L4*). In this reaction, medium to high levels of enantioselectivities were observed.     

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

Cyclobutenones, four‐membered ketones bearing an unsaturated carbon–carbon double bond, and their structural sibling benzocyclobutenones, possess unique reactivity. Owing to their inherent high ring strain, such structures readily undergo ring opening under a variety of conditions, including thermolysis, photolysis, and transition metal catalysis, to afford reactive intermediates that can be trapped with nucleophiles, dienophiles, and unsaturated bonds. Their electron‐deficient enone moieties are good electrophiles for facile nucleophilic addition. Such properties render cyclobutenones versatile synthons, serving as excellent coupling partners in a vast array of synthetically valuable transformations.     

Chloromethyl Glycosides as Versatile Synthons to Prepare Glycosyloxymethyl-Prodrugs

This work investigates the addition of monosaccharides to marketed drugs to improve their pharmacokinetic properties for oral absorption. To this end, a set of chloromethyl glycoside synthons were developed to prepare a variety of glycosyloxymethyl-prodrugs derived from 5-fluorouracil, thioguanine, propofol and losartan. Drug release was studied in vitro using β-glucosidase confirming rapid conversion of the monosaccharide prodrugs to release the parent drug, formaldehyde and the monosaccharide. To showcase this prodrug approach, a glucosyloxymethyl conjugate of the tetrazole-containing drug losartan was used for in vivo experiments and showed complete release of the drug in a dog-model.     

Furanose Bicyclophosphites as Synthons of Modified Nucleoside Diphosphates

Abstract

Previously we synthesized and examined in detail 1,2- alkylideneglucofuanose 3,5,6-bicyclophosphites; mono- and bicyclophosphates with peculiar chemical and physiological activity were obtained on their base [1]. During the study of their structural dependence, we modified the hydrocarbonic moiety, synthesiz-ed 1,2,3- and 3,5,6-bicyclophosphites and cyclophosphates of gulofuanose, and correlated their features with those of glucose analogues. Furthermore, an additional phosphonate moiety (obtained by a stereoselective reaction of an appropriate ketonic sugar with silylphosphites) was introduced into the glucofuranose 3,5,6-bicyclophosphite molecule to the third carbon atom. As a result, the monosaccharide matrix gained two functional groups containing tri- and fourcoordinated phosphorus.     

Enaminones as Synthons for a Directed C−H Functionalization: RhIII‐Catalyzed Synthesis of Naphthalenes

The use of enaminones as effective synthons for a directed C?H functionalization is reported. Proof‐of‐concept protocols have been developed for the Rh^III‐catalyzed synthesis of naphthalenes, based on the coupling of enaminones with either alkynes or α‐diazo‐β‐ketoesters. Two inherently reactive functionalities (hydroxy and aldehyde groups) are integrated into the newly formed cyclic framework and a broad range of substituents are tolerated, rendering target products readily available for further elaboration.     

光学活性C3合成子的不对称合成及应用

叙述了光学活性甘油醇及其衍生物等手性Ｃ３合成的合成方法,以及这些手性化合物在不对称有机合成中的应用,参考文献２４篇。     

A Study on Synthesis and Upscaling of 2′-O-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis

2′-O-(N-(Aminoethyl)carbamoyl)methyl-modified 5-methyluridine (AECM-MeU) and 5-methylcytidine (AECM-MeC) phosphoramidites are reported for the first time and prepared in multigram quantities. The syntheses of AECM-MeU and AECM-MeC nucleosides are designed for larger scales (approx. 20 g up until phosphoramidite preparation steps) using low-cost reagents and minimizing chromatographic purifications. Several steps were screened for best conditions, focusing on the most crucial steps such as N³ and/or 2′-OH alkylations, which were improved for larger scale synthesis using phase transfer catalysis (PTC). Moreover, the need of chromatographic purifications was substantially reduced by employing one-pot synthesis and improved work-up strategies.     

Novel Bis-arylPheDOT Synthons for Electrochromic Polymers

Two terthiophenes incorporating the synthon 3,4-(1,2-phenylenedioxy)thiophene (PheDOT) have been developed. Specifically, 2,5-bisthienyl-3,4-(1,2-phenylenedioxy)thiophene (BTh-PheDOT 1) and 2,5-bisethylenedioxythienyl-3,4-(1,2-phenylenedioxy)thiophene (BEDOT-PheDOT 2) were electropolymerized to form electroactive polymer films (P1 and P2) that switched between two highly colored states with the more electron-rich EDOT derivative P2 observed to switch at a lower potential. Additionally, both P1 and P2 displayed moderate to low optical bandgaps of 1.8 and 1.6 eV, respectively. Crystal structures of BTh-PheDOT showed the monomer to be nearly planar with π -stacking observable between monomers. These findings demonstrate the potential of PheDOT as an electroactive synthon for the formation of well-ordered systems.     

Synthesis of Polynucleotide Modified Gold Nanoparticles as a High Potent Anti‐Cancer Drug Carrier

Gold nanoparticles have been developed for the photoacoustic imaging, delivery of genes and laser induced photothermal therapy. In this study, we have developed oligonucleotide conjugated gold nanoparticles as the carrier for simultaneous DNA and anti‐cancer nucleoside delivery. The polynucleotidenanoparticle complex presented higher capacity in carrying 5‐FU anti‐cancer compounds than the original gold particles. The hydrodynamic size of the gold nanoparticles increased from 25 to 35 nm with an increase in the negative surface charge from ?9.58 to 21.66 mV after polynucleotide conjugation and drug loading. A positive association between environmental pH and drug release was observed in PBS, which implied their potential use in the controlled localized drug release in the lower GI tract. The MTT assay revealed dose dependent cytotoxicity to colon cancer cell line than free compounds. These results suggest the potential use of this new polynucleotide‐gold nanoparticles complex as the environmental controlled anti‐cancer nanocapsule, especially suitable for per oral colon cancer chemotherapy.     

Phosphorylacetaladehydes in Reactions with N-Electro-Philes. Synthesis of new Promising Synthons

Abstract

The reactions of phosphorylacetaldehydes I with N-electro-philes (⁺NO, ⁺N₂Ar) proceed selectively via intermediate A in accordance with one of the three directions depending on the nature of the substituents X and R. The nature of the end product is determined by the competitive electrofugic power of R₂P(O), X and CHO.