Bis(o-nitrophenyl)ethanediol: A practical photolabile protecting group for ketones and aldehydes

The ketals of bis(o-nitrophenyl)ethanediol and ketones or aldehydes are smoothly deprotected in neutral conditions by irradiation with 350 nm light. The chemical stability in basic, acidic, and oxidizing media makes this form of protection orthogonal to classical protecting groups. Both racemic and enantiopure forms are readily available in two steps from inexpensive starting materials.     

Anthraquinon-2-ylethyl-1′,2′-diol (Aqe-diol) as a new photolabile protecting group for aldehydes and ketones

A new photolabile protecting group for aldehydes and ketones, 2-(1,2-dihydroxyethyl) anthraquinone (Aqe-diol) and four caged compounds have been prepared and their photochemistry investigated. Upon 350 nm light irradiation, the caged compounds 2a-d in CH₃CN–H₂O solution can efficiently release the carbonyl compounds (conversion rate 60–90%), and their uncaging quantum efficiencies were measured, ranging from 0.03 to 0.09. On the basis of HPLC analysis and quenching experiments, a mechanism of the uncaging reaction was suggested.     

Bis(4,5-dimethoxy-2-nitrophenyl)ethylene glycol: a new and efficient photolabile protecting group for aldehydes and ketones

Synthesis of a new photolabile protecting group, bis(4,5-dimethoxy-2-nitrophenyl)ethylene glycol (4) from 4,5-dimethoxy-2-nitrobenzyl alcohol in three steps in good yields is described. The acetals and ketals of 4 are stable against acidic and basic reaction conditions and are cleaved smoothly on irradiation at 350 and 400 nm with regeneration of carbonyl compounds in high yields and efficiency.     

Oxidation with a photolabile carbonyl protecting group

A novel oxidation approach utilizing a robust photolabile carbonyl protecting group reagent (1) as the oxidizing reagent has been developed. Different from existing methods, this approach oxidizes primary alcohols to the photosensitive acetals (e.g., 3), providing another unique approach to the protected aldehydes. Thus, for the first time, oxidation and protection are achieved in one reaction. Secondary alcohols are oxidized to the corresponding ketones. Moreover, the photolabile protecting group (PPG) also oxidizes ethers and esters. The oxidation is presumably via hydride abstraction by the tritylium ion generated from 1 under acidic conditions. However, the mechanisms for primary alcohols and secondary alcohols are slightly different.     

New safety-catch photolabile protecting group

Photolabile protecting groups have proven their usefulness on many occasions. Their versions as linkers are however less attractive, as robustness and real orthogonality become critical issues. Safety-catch systems, where a preliminary activation phase is necessary, circumvent the problem of premature cleavage. In this work, we introduce a new safety-catch photolabile protecting group, whose cleavage requires the simultaneous presence of light and a chemical promoter.     

Novel photolabile protecting group for carbonyl compounds

[reaction: see text] A novel type of photo-protecting group for carbonyl compounds is described. The protecting group is readily accessed in one step from commercially available material. Installation of the protecting group upon the carbonyl compounds is achieved in excellent yields. The carbonyl compounds in their protected form are remarkably stable under various conditions and can be released photochemically in high efficiency.     

Brominated hydroxyquinoline as a photolabile protecting group with sensitivity to multiphoton excitation

The synthesis and photochemistry of a new photolabile protecting group for carboxylic acids based on 8-bromo-7-hydroxyquinoline (BHQ) is described. BHQ possesses a greater single photon quantum efficiency than 4,5-dimethoxy-4-nitrobenzyl ester (DMNB) and 6-bromo-7-hydroxycoumarin-4-ylmethyl (Bhc), and it has sufficient sensitivity to multiphoton-induced photolysis for use in vivo. Its increased solubility and low fluorescence make it quite useful as a caging group for biological messengers. [structure: see text]     

2-Hydroxy-1,2,2-triphenylethanone as an efficient photolabile protecting group for carboxylic acids

The synthesis is reported of 2-hydroxy-1,2,2-triphenylethanone esters of carboxylic acids by the reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Photolysis of the esters occurs rapidly on irradiation with a medium-pressure mercury lamp through quartz or Pyrex to return the carboxylic acid. The side product of the photolysis is benzo[b]phenanthro[9,10-d]furan, formed through a tandem process involving initial generation of 2,3-diphenylbenzofuran, photochemical cyclisation and re-aromatisation by aerial oxidation.     

A new photolabile carboxyl protecting group for native chemical ligation

Native chemical ligation (NCL) at Glu-Cys sites requires carboxyl protection that is compatible with the chemistry used for assembling the peptides. In the case of Fmoc-chemistry our novel BCMACM-group is particularly suitable for NCL because of the good solubility in aqueous solvent systems and mild conditions of photolytic removal.     

Synthesis and application of an IL-supported diol as protecting group for aldehydes

A new IL-supported diol,1-(2,3-dihydroxypropyl)-3-methylimidazolium hexafluorophosphate has been synthesized and char- acterized by FT-IR,~1H NMR,~(13)C NMR and MS (ESI).Its physical properties such as freezing point,solubility and specific gravity and thermal stability were determined.Synthetic utilities of the resultant diol as a protecting group for aldehydes were also investigated.     

A strategy for the construction of caged diols using a photolabile protecting group

Caged analogues of biologically active compounds have received widespread attention as temporally and spatially controlled probes of cell-based processes. Recently, a coumarin-4-ylmethyl derivative has been used to cage carboxylates, sulfonates, carbamates, and phosphates. We describe herein a synthetic strategy that furnishes photosensitive caged diols and provides an entry into the protection/photodeprotection of functionality with modest leaving group abilities.     

Nin-cyclohexyloxycarbonyl group as a new protecting group for tryptophan

Several new protecting groups were introduced at the Nⁱⁿ-position of tryptophan, and their reactivities were examined under the conditions used for peptide synthesis by Boc-strategy. Among them, the cyclohexyloxycarbonyl (Hoc) group was found to be the most suitable in terms of stability during elongation of the peptide chain and removability at the final HF reaction without resorting to the use of thiols.     

Application of the excited state meta effect in photolabile protecting group design

A novel photolabile protecting group for carbonyl compounds has been developed, based on the excited state meta effect.     

Rapid one-pot iterative diselenide–selenoester ligation using a novel coumarin-based photolabile protecting group

The development of an iterative one-pot peptide ligation strategy is described that capitalises on the rapid and efficient nature of the diselenide–selenoester ligation reaction, together with photodeselenisation chemistry. This ligation strategy hinged on the development of a novel photolabile protecting group for the side chain of selenocysteine, namely the 7-diethylamino-3-methyl coumarin (DEAMC) moiety. Deprotection of this DEAMC group can be effected in a mild, reagent-free manner using visible light (λ = 450 nm) without deleterious deselenisation of selenocysteine residues, thus enabling a subsequent ligation reaction without purification. The use of this DEAMC-protected selenocysteine in iterative DSL chemistry is highlighted through the efficient one-pot syntheses of 60- and 80-residue fragments of mucin-1 as well as apolipoprotein CIII in just 2–4 hours.

A method for the rapid one-pot iterative assembly of proteins via diselenide–selenoester ligation (DSL) chemistry is described that capitalises on a novel coumarin-based photolabile protecting group for selenocysteine.     

Development of the 8-aza-3-bromo-7-hydroxycoumarin-4-ylmethyl group as a new entry of photolabile protecting groups

A significant substitution effect of the position of the bromo group on the photosensitivity of the 8-azacoumarin chromophore leads to the development of a highly photosensitive 8-aza-3-bromo-7-hydroxycoumarin-4-ylmethyl (aza-3-Bhc) group that shows excellent photolytic efficiency and hydrophilicity with long-wavelength absorption maxima. The newly identified aza-3-Bhc group can be applied to caged glutamates for ester-type and carbamate-type protections of carboxyl and amino functionalities.     

Synthetic talc as a solid base catalyst for condensation of aldehydes and ketones

Magnesium organo silicates (MOSs; synthetic talc) as such and with amine surface functionalities were synthesized by sol–gel method under non-hydrothermal conditions and characterized by spectroscopic techniques. The synthesized talc samples were observed to be thermally stable up to 200 °C in nitrogen atmosphere and used as catalysts for condensation of aldehydes and ketones. Application of synthetic talc as a solid base catalyst for condensation of aldehydes and ketones is being reported for the first time. The effect of solvent, solvent to reactant molar ratio, amount of catalyst and temperature was studied in detail for self-condensation of propanal. High conversion (86%) of propanal with 95% selectivity of 2-methylpentenal was achieved using dimethyl sulphoxide as a solvent. The kinetic study was carried out for the condensation of propanal catalyzed by amine functionalized MOS under optimum reaction conditions. Catalyst was re-used without significant loss in activity up to three cycles.     

Thietane ring as a novel protecting group

A novel protecting group for NH functionality of heterocycles, a thietane ring, was proposed. It can be readily introduced by alkylation of NH-heterocycles with 2-chloromethylthiirane. Removal of the thietane protecting group is performed via oxidation to thietane 1,1-dioxide with hydrogen peroxide in acetic acid and subsequent treatment with sodium alkoxide.     

Ammonia borane as a metal free reductant for ketones and aldehydes: a mechanistic study

Without a catalyst ketones and aldehydes were reacted in THF with ammonia borane (AB) to proceed hydroboration forming alkyl borates. Mechanistic studies revealed that dissociation of ammonia from AB occurred before the hydroboration step. When methanol was used as the solvent, metal free methanolysis of AB would take place with the ketone/aldehyde being directly hydrogenated by the MeOH·BH₃ complex.     

Development of trityl-based photolabile hydroxyl protecting groups

A series of trityl-based photolabile hydroxyl protecting groups have been examined. These PPGs evolve from the traditional acid-labile trityl protecting group with proper electron-donating substituents. Structure-reactivity relationships have been explored. A m-dimethylamino group is crucial to achieve high photochemical deprotection efficiency. The o-hydroxyl group in 8 greatly improves the yield of the photochemical deprotection reaction, compared with the corresponding o-methoxyl-substituted counterpart 7. However, comparison between the photoreactions of 9 and 11 does not show similar structural relevance. The PPG in ether 1 (i.e., DMATr group) is structurally simple and easy to prepare and install. Its deprotection can be successfully carried out with irradiation of sunlight without requirement of photochemical devices.