Deprotection Of Functional Groups Research Articles

Biodegradable Block Poly(ester amine)s with Pendant Hydroxyl Groups for Biomedical Applications.

The article presents the results of the synthesis and characteristics of the amphiphilic block terpolymers, built of a hydrophilic polyesteramine block, and hydrophobic blocks made of lactidyl and glycolidyl units. These terpolymers were obtained during the copolymerization of L-lactide with glycolide carried out in the presence of previously produced macroinitiators with protected amine and hydroxyl groups. The terpolymers were prepared to produce a biodegradable and biocompatible material containing active hydroxyl and/or amino groups, with strong antibacterial properties and high surface wettability by water. The control of the reaction course, the process of deprotection of functional groups, and the properties of the obtained terpolymers were made based on 1H NMR, FTIR, GPC, and DSC tests. Terpolymers differed in the content of amino and hydroxyl groups. The values of average molecular mass oscillated from about 5000 g/mol to less than 15,000 g/mol. Depending on the length of the hydrophilic block and its composition, the value of the contact angle ranged from 50° to 20°. The terpolymers containing amino groups, capable of forming strong intra- and intermolecular bonds, show a high degree of crystallinity. The endotherm responsible for the melting of L-lactidyl semicrystalline regions appeared in the range from about 90 °C to close to 170 °C, with a heat of fusion from about 15 J/mol to over 60 J/mol.

The versatility of DABCO as a reagent in organic synthesis: a review.

DABCO (1,4-diazabicyclo[2.2.2]octane) has garnered a lot of interest for numerous organic transformations since it is a low-cost, environmentally friendly, reactive, manageable, non-toxic and basic organocatalyst with a high degree of selectivity. Moreover, DABCO functions as a nucleophile as well as a base in a variety of processes for the synthesis of a wide array of molecules, including carbocyclic and heterocyclic compounds. Protection and deprotection of functional groups and the formation of carbon-carbon bonds are also catalyzed by DABCO. The reagent also finds applications in the synthesis of functional groups like isothiocyanate, amide and ester. Application of DABCO in cycloaddition, coupling, aromatic nucleophilic substitution, ring-opening, oxidation and rearrangement reactions is also noteworthy. This is a state of the art review that has encompassed a variety of processes for the synthesis of organic frameworks using DABCO.

Multiwavelength Control of Mixtures Using Visible Light-Absorbing Photocages.

Selective deprotection of functional groups using different wavelengths of light is attractive for materials synthesis as well as for achieving independent photocontrol over substrates in biological systems. Here, we show that mixtures of recently developed visible light-absorbing BODIPY-derived photoremovable protecting groups (PRPGs) and a coumarin-derived PRPG can undergo wavelength-selective activation, giving independent optical control over a mixture of photocaged substrates using biologically benign long-wavelength light.

Biased photo cleavage of N1-/N6-nitrobenzyl from 2’-hydroxyethyl-adenosine and their DNA/RNA Caged-analogues

The protection and deprotection of functional groups are critical steps during the synthesis of complex molecules. The chemo-selective and regio-selective protection-deprotection under mild conditions are always preferred. The photolabile protecting groups have such qualities. For example, o-nitrobenzyl is a versatile photolabile protecting group of amine, alcohol, and carboxylic acid. This report describes the regio-selective N-nitrobenzylation of 2′-tethered-adenosine nucleoside analogue with o-nitrobenzyl bromide, as resultant two new protected nucleosides such as 2′-hydroxylethyl-NBn1A/2′-hydroxylethyl-NBn6A are prepared. Importantly, N-nitrobezylation occurs only at adenine residue, though it is protected. This analogue has a free tethered hydroxyl group at 2′-position and remained unaffected with nitrobenzylation. Furthers, these analogues are incorporated into DNA/RNA oligonucleotides using DNA synthesizer. This report also demonstrates the photocleavage of those nitrobenzyl groups in a regio-specific manner by UV-light (λ365nm). The nitrobenyl of only NBn6A derivatives are cleavable regio-specifically with UV-light. Surprisingly, unusual chemical cleavage of nitrobenzyl of NBn1A-DNA/RNA has found during oligo syntheses. Also, the isomerization of NBn1A-DNA into NBn6A-DNA occurs. Thus only NBn6A derivatives are caged-adenosine analogues. Hence 2′-tethered-NBn6A/-NBn1A derivatives are potential analogues for regulating the biochemical activities with light.

Enzymatic glycosylation of 4'-demethylepipodophyllotoxin

The glycosides of 4'-demethylepipodophyllotoxin (DMEP) possess various pharmacological activities; however, the chemical synthesis of these glycosides faces challenges in regioselectivity, stereoselectivity, and the protection and de-protection of functional groups. In this work, a novel glycosyltransferase (GT) gene AbGT5 from Aloe barbadensis was successfully cloned, heterogeneously expressed and purified. Recombinant AbGT5 was able to catalyze the glycosylation of DMEP and the glycosylated product, which was separated from the preparative scale reaction, was characterized as DMEP 4'-O-β-D-glucoside via MS, 1H-NMR, 13C-NMR, HSQC and HMBC. According to the investigations of enzyme properties, AbGT5 show the highest activity around 20 ℃ in the buffer of pH 9.0, and it was independent of divalent metal ions. Under the optimum conditions, the conversion rate of DMEP can reach 80%. Above all, in this work the enzymatic glycosylation of DMEP was achieved with high efficiency by the novel GT AbGT5.

Synthetics Methods for the Preparation of Biaryls

The biaryl structural unit is often found in natural products, pharmaceuticals and agrochemicals. Therefore, the formation of the carbon-carbon bond is of extreme importance in the synthetic planning of substances. Many methods of obtaining biaryls are described in the literature, however, nickel or palladium catalyzed cross-coupling methodologies such as Kuma-Tamao-Corriu, Negishi, Migita-Kosug-Stille, Suzuki-Miayura and Hiyama are the most important and most used tools today. These reactions avoid the need for protection and deprotection of functional groups, as they are tolerant to most groups, such as: aldehydes, ketones, amino, nitriles, hydroxides, esters and nitro group. In this work, these cross-coupling methodologies and their main characteristics will be discuss.

Synthesis of Mirabiquinone A: A Biquinone from the Sea Urchin Scaphechinus mirabilis and Related Compounds

The first total synthesis of mirabiquinone A (2,3,5,6,8,10,11,13-octahydroxy-7-methyl-1H-dibenzo[b,h]xanthene-1,4,9,12(7H)-tetraone) produced by the sea urchin Scaphechinus mirabilis is described. This was achieved by cyclization of 6,6′-ethylidenebis(7-hydroxy-2,3-dimethoxynaphthazarin) or its mono- or dimethoxy derivatives and functional group deprotection. The synthesis of methyl analogues of mirabiquinone A is also described.

ChemInform Abstract: Development of Fluorescent Probes Based on Protection—Deprotection of the Key Functional Groups for Biological Imaging

AbstractReview: 50 refs.

Short syntheses of (+)-ferruginol from (+)-dehydroabietylamine

Short syntheses of bioactive (+)-ferruginol in five or six synthetic steps starting from commercially available (+)-dehydroabietylamine are described. The oxygenated function at C12 was introduced via a Friedel–Crafts acylation of N-phthaloyldehydroabietylamine followed by Baeyer–Villiger oxidation. Then, overall deprotection of functional groups, reductive deamination or biomimetic oxidative deamination, and final Wolff–Kishner reduction provided (+)-ferruginol in 21 and 23% overall yields, respectively.

Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin

AbstractThe racemic and enantiodivergent syntheses of 1‐deoxymannojirimycin (DMJ) and 1,4‐dideoxymannojirimycin have been realized through key enamide ester intermediates obtained by converting cis‐4,5‐dihydroxylated δ‐valerolactam derivatives into the corresponding enol phosphates and subjecting them to Pd‐catalyzed methoxycarbonylation. Further elaborations of these intermediates included stereocontrolled catalytic hydrogenation, for the synthesis of racemic 1,4‐dideoxymannojirimycin, and hydroboration/oxidation, for the synthesis of DMJ. Enantiodivergency was attained by optical resolution before exhaustive functional group deprotection, through the formation of diastereomeric camphanic esters. As the key racemic intermediate esters were easily prepared in a few steps on a large scale, and the final chromatographic separation of the camphanic esters was straightforward, this approach represents a convenient way to obtain both enantiomers of DMJ for medicinal chemistry studies.

Synthesis of molecular photoswitches based on azobenzene with an organosilane anchor

The incorporation of photoactive molecules in thin layers enables photoinduced changes in wettability, e.g. azobenzenes, or micropatterning by deprotection of functional groups, e.g. applying nitroveratryl compounds. This paper describes a synthetic route for obtaining an azobenzene with a silane anchor. The chemical synthesis, including all intermediates, is characterized by NMR and IR. The photoisomerization of all products was investigated by UV/Vis spectroscopy. Ellipsometry and contact angle measurements give information about monolayers of the synthesized organosilanes.

Biocatalysis in development of green pharmaceutical processes

Biocatalysis is one of the greenest technologies for the synthesis of chiral molecules due to exquisite regioselectivity and stereoselectivity in water under mild conditions. For example, protection and deprotection of functional groups are usually not required for biotransformations, high or low temperature reactions can often be circumvented and usage of organic solvents are drastically minimized. To truly empower the green chemistry feature of biocatalysis, it is essential to integrate enzymatic transformations strategically into chemical transformations at the retrosynthetic level. This review focuses on the development of novel biocatalytic pharmaceutical processes to replace chemical routes with poorer process efficiency and higher manufacturing costs.

Molecular Iodine in Protection and Deprotection Chemistry

The various reactions involving the protection and deprotection of functional groups effected by molecular iodine are described here.

Some applications of zirconium(IV) tetrachloride (ZrCl4) and zirconium(IV) oxydichloride octahydrate (ZrOCl2.8H2O) as catalysts or reagents in organic synthesis

Both ZrCl4 and ZrOCl2.8H2O are commercially available solid chemicals. Due to their low toxicities (LD50 [ZrCl4 oral rate] = 1688 mg/kg), (LD50 [ZrOCl2.8H2O oral rate] = 2950 mg/kg), low costs, ease of handling, high activity, the zirconium(IV) compounds are potential green catalysts or reagents which are of importance from different views. In this review we have paid attention to the applications of these compounds as reagents or catalysts in Friedel-Crafts reactions, Fries rearrangements, reduction and oxidation reactions, cycloaddition and hydrometalation reactions, protection and deprotection of functional groups, reactions of epoxides, iodination of alcohols, S-alkylation of thiols with alcohols, Michael addition, condensation of indoles with carbonyl compounds, Claisen ester condensation, Baylis-Hillman reaction, preparation of organozirconium compounds and some other miscellaneous reactions.

Synthesis of Echinamines A and B, the First Aminated Hydroxynaphthazarins Produced by the Sea Urchin Scaphechinus mirabilis and Its Analogues

The first total synthesis of two marine aminated hydroxynaphthazarins, echinamines A (3-amino-7-ethyl-2,5,6,8-tetrahydroxy-1,4-naphthoquinone) and B (2-amino-7-ethyl-3,5,6,8-tetrahydroxy-1,4-naphthoquinone), produced by the sea urchin Scaphechinus mirabilis is described. This was achieved from 1,2,4-triacetoxybenzene (13) through a sequence involving double Fries rearrangement of 13, reduction of 3,5-diacetyl-1,2,4-trihydroxybenzene (14), methylation of 3,5-diethyl-1,2,4-trihydroxybenzene (15), simultaneous double acylation of 3,5-diethyl-1,2,4-trimethoxybenzene (16) with a dichloromaleic anhydride-ethyl radical elimination process, methylation of 6,7-dichloro-3-ethyl-2-hydroxynaphthazarin (17), nucleophilic substitution of a chlorine atom by the methoxy group in 6,7-dichloro-3-ethyl-2-methoxynaphthazarin (18), introduction of an amino group via direct substitution of a chlorine atom in 7-chloro-3-ethyl-2,6-dimethoxy- (11) and 7-chloro-2-ethyl-3,6-dimethoxynaphthazarins (12) by an azido group, and functional group deprotection. The synthesis of amino analogues of spinazarin and spinochrome D is also described.

Control of four stereocentres in a triple cascade organocatalytic reaction

Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centres continue to be important in both academic and industrial laboratories. In particular, catalytic asymmetric multi-component 'domino' reactions, used during total syntheses of natural products and synthetic building blocks, are highly desirable. These reactions avoid time-consuming and costly processes, including the purification of intermediates and steps involving the protection and deprotection of functional groups, and they are environmentally friendly and often proceed with excellent stereoselectivities. Therefore, the design of new catalytic and stereoselective cascade reactions is a continuing challenge at the forefront of synthetic chemistry. In addition, catalytic cascade reactions can be described as biomimetic, as they are reminiscent of tandem reactions that may occur during biosyntheses of complex natural products. Here we report the development of an asymmetric organocatalytic triple cascade reaction for the synthesis of tetra-substituted cyclohexene carbaldehydes. This three-component domino reaction proceeds by way of a catalysed Michael/Michael/aldol condensation sequence affording the products with good to moderate yields (25-58 per cent). During this sequence, four stereogenic centres are formed with high diastereoselectivity and complete enantioselectivity. In addition, variation of the starting materials can be used to obtain diverse polyfunctional cyclohexene derivatives, which can be used as building blocks in organic synthesis.

Simplified Scheme for Deterministic Synthesis of Chiral-Nematic Glassy Liquid Crystals

Potentially useful for the fabrication of nonabsorbing polarizers, optical notch filters and reflectors, and polarized light sources, chiral-nematic glassy liquid crystals can be synthesized by a statistical or deterministic approach. A deterministic approach is characterized by the relative ease of product separation and purification and hence is more amenable to process scale-up. Prompted to minimize the effort involving protection and deprotection of functional groups, the present work has demonstrated the feasibility of reducing the number of synthesis steps from a previous synthesis scheme. The new methodology is widely applicable to the synthesis of a variety of right- and left-handed chiral-nematic glassy liquid crystals with desired phase transition temperatures.

Short and efficient enantioselective total synthesis of angucyclinone type antibiotics (+)-rubiginone B2 and (+)-ochromycinone

The enantioselective total synthesis of antibiotics rubiginone B2 and ochromycinone is achieved from enantiopure (S)-5-methoxy-2-(p-tolylsulfinyl)-1,4-naphthoquinone and a racemic vinylcyclohexene through a short sequence involving a tandem Diels–Alder reaction–sulfoxide elimination process with simultaneous kinetic resolution of the racemic diene, followed by controlled aromatization and functional group deprotection.

Synthesis of Thione Analogues of Monobactams

AbstractOptically active β‐lactams 4 were treated with Lawesson's reagent (2) or Davy's reagent (3) to give the β‐thiolactams 5. Demethylation of 5 by reduction with dissolved metal gave the 1‐unsubstituted 2‐azetidinethiones 6 which were sulfonated and Boc‐deprotected to provide (3S)‐amino‐2‐thiomonobactamic acids 8. The side chain on nitrogen was introduced by using 1‐hydroxybenzotriazole‐activated acids 9. Deprotection of functional groups in the side chain yielded the β‐thiolactam analogues 11a, 11b of SQ 81,377 and aztreonam (1). These compounds were found to be weakly active against a range of Gram‐negative bacteria.

Hexafluoroacetone in deep UV resist chemistry: new resins, dissolution inhibitors and crosslinkers.

Some recent investigations on hexafluoroacetone (HFA) have revealed that this reagent offers a variety of interesting aspects and potential applications for new photoresist products. The 2- hydroxyhexafluoroisopropyl group (HHFIP), obtained via condensation reaction of HFA with aromatic compounds, exhibits properties comparable to phenolic groups with respect to reactivity and acidity. This allows transfer of a variety of chemistries presently exclusively linked to phenol-type compounds, such as reversible blocking, to HHFIP substituted compounds, resulting in alkali-soluble matrix resins, polymer functional group deprotection materials, or dissolution inhibition, and crosslinking type materials. In contrast to phenols, the electron density of the aryl group is reduced due to the electron-withdrawing properties of the HHFIP group, resulting in materials with significantly changed reactivities of the aromatic moieties.