Oxobenzo[f]benzopyrans as new fluorescent photolabile protecting groups for the carboxylic function

The properties of three oxobenzo[f]benzopyrans as new fluorogenic photolabile protecting groups for the carboxylic function of amino acids were studied. Fluorescent amino acid conjugates were efficiently prepared and characterised. Photodeprotection of these compounds was carried out by irradiation at 300, 350 and 419 nm, the most suitable wavelength being 350 nm, on account of short irradiation times and good deprotection yields.     

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.     

A new protecting group for the exocyclic amino groups of nucleosides

A new protecting group has been developed for the exocyclic amino groups of nucleosides that occur in DNA. 3-Phenyl-[{N-(2-trimethylsilyl-ethoxycarbonyl)-2-amino}]-propanoic acid used as the protective agent.     

Intramolecular sensitization of photocleavage of the photolabile 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protecting group: photoproducts and photokinetics of the release of nucleosides

Novel photolabile protecting groups based on the 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) group with a covalently linked thioxanthone as an intramolecular triplet sensitizer exhibit significantly enhanced light sensitivity under continuous illumination. Herein we present a detailed study of the photokinetics and photoproducts of nucleosides caged with these new protecting groups. Relative to the parent NPPOC group, the light sensitivity of the new photolabile protecting groups is enhanced by up to a factor of 21 at 366 nm and is still quite high at 405 nm, the wavelength at which the sensitivity of the parent compound is practically zero. A new pathway for deprotection of the NPPOC group proceeding through a nitroso benzylalcohol intermediate has been discovered to complement the main mechanism, which involves beta elimination. Under standard conditions of lithographic DNA-chip synthesis, some of the new compounds, while maintaining the same chip quality, react ten times faster than the unmodified NPPOC-protected nucleosides.     

4-Acetoxy-2,2-dimethylbutanoate: a useful carbohydrate protecting group for the selective formation of β-(1→3)-d-glucans

The use of 4-acetoxy-2,2-dimethylbutanoyl protecting group for the C2-hydroxyl allows the selective formation of β-glycosides without producing α-glycosides. This very bulky protecting group can be removed under mild conditions.     

Aryldithioethyloxycarbonyl (Ardec): a new family of amine protecting groups removable under mild reducing conditions and their applications to peptide synthesis

The development of phenyldithioethyloxycarbonyl (Phdec) and 2-pyridyldithioethyloxycarbonyl (Pydec) protecting groups, which are thiol-labile urethanes, is described. These new disulfide-based protecting groups were introduced onto the epsilon-amino group of L-lysine; the resulting amino acid derivatives were easily converted into N alpha-Fmoc building blocks suitable for both solid- and solution-phase peptide synthesis. Model dipeptide(Ardec)s were prepared by using classical peptide couplings followed by standard deprotection protocols. They were used to optimize the conditions for complete thiolytic removal of the Ardec groups both in aqueous and organic media. Phdec and Pydec were found to be cleaved within 15 to 30 min under mild reducing conditions: i) by treatment with dithiothreitol or beta-mercaptoethanol in Tris.HCl buffer (pH 8.5-9.0) for deprotection in water and ii) by treatment with beta-mercaptoethanol and 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU) in N-methylpyrrolidinone for deprotection in an organic medium. Successful solid-phase synthesis of hexapeptides Ac-Lys-Asp-Glu-Val-Asp-Lys(Ardec)-NH2 has clearly demonstrated the full orthogonality of these new amino protecting groups with Fmoc and Boc protections. The utility of the Ardec orthogonal deprotection strategy for site-specific chemical modification of peptides bearing several amino groups was illustrated firstly by the preparation of a fluorogenic substrate for caspase-3 protease containing the cyanine dyes Cy 3.0 and Cy 5.0 as FRET donor/acceptor pair, and by solid-phase synthesis of an hexapeptide bearing a single biotin reporter group.     

Propargyloxycarbonyl as a protecting group for the side chains of serine, threonine and tyrosine

Propargyloxycarbonyl group is used as a protecting group for the hydroxyl groups of serine, threonine and tyrosine. The propargyloxycarbonyl derivatives of these hydroxy amino acids are stable to acidic and basic reagents commonly employed in peptide synthesis. The deprotection of the O-Poc derivatives using tetrathiomolybdate does not affect commonly used protecting groups such as N-Boc, N-Cbz, N-Fmoc, methyl and benzyl esters. The di-and tripeptides synthesized using O-Poc derivatives of serine, threonine and tyrosine are stable, isolable compounds and give the hydroxy peptides in good yields when treated with tetrathiomolybdate.     

A novel, base-labile fluorous amine protecting group: synthesis and use as a tag in the purification of synthetic peptides

A new, base-labile fluorous tag based on the Msc amine protecting group was synthesized. Its use in the purification of synthetic peptides by fluorous HPLC or fluorous SPE was demonstrated.     

Use of p-nitrobenzyloxycarbonyl (pNZ) as a permanent protecting group in the synthesis of Kahalalide F analogs

p-Nitrobenzyloxycarbonyl (pNZ) is used for the permanent protection of ornithine in the synthesis of derivatives of the anti-tumor cyclodepsipeptide Kahalalide F that contain acid labile residues.     

BH3 as a protecting group for phosphonic acid: a novel method for the synthesis of dinucleoside H-phosphonate

A BH₃ group is found to be an effective protecting group for phosphonic acid esters. This new phosphonic acid protecting group was applied to the synthesis of a dithymidine H-phosphonate derivative from a dithymidine boranophosphate derivative. Triarylmethyl cations were found to be effective for the deprotection of the BH₃ group in the dithymidine boranophosphate diester to afford the corresponding H-phosphonate derivative in excellent yield.     

Nitropyrazoles 16. The use of methoxymethyl group as a protecting group for the synthesis of 4-methyl-3-nitro-5-R-pyrazoles

4-Methyl-3,5-dinitropyrazole prepared by nitration of 1,4-dimethylpyrazole readily reacts with methoxymethyl chloride and methyl vinyl ketone in acetonitrile in the presence of a base giving 1-methoxymethyl-4-methyl-3,5-dinitropyrazole and 4-methyl-3,5-dinitro-1-(3-oxobutyl)pyrazole, respectively. The action of the thioglycolanilide anion on 4-methyl-3,5-dinitro-1-(3-oxobutyl)pyrazole results only in the removal of 1-protecting group and the formation of 2-[(3-oxobutyl)thio]acetanilide, while the action of anionic S-nucleophiles on 1-methoxymethyl-4-methyl-3,5-dinitropyrazole leads to the substitution products of the 5-NO₂ group in which the methoxymethyl group can be removed by acid hydrolysis.     

Efficient tandem process for the catalytic deprotection of N-allyl amides and lactams in aqueous media: a novel application of the bis(allyl)-ruthenium(IV) catalysts [Ru(eta3:eta2:eta3-C12H18)Cl2] and [{Ru(eta3:eta3-C10H16)(micro-Cl)Cl}2

An operationally simple and highly efficient methodology for the removal of the allyl protecting group in amides and lactams has been developed by using the commercially available bis(allyl)-ruthenium(IV) catalysts [Ru(eta(3):eta(2):eta(3)-C(12)H(18))Cl(2)] (C(12)H(18)=dodeca-2,6,10-triene-1,12-diyl) and [{Ru(eta(3):eta(3)-C(10)H(16))(micro-Cl)Cl}(2)] (C(10)H(16)=2,7-dimethylocta-2,6-diene-1,8-diyl). The tandem process, which takes place in aqueous media and proceeds in a one-pot manner, involves the initial isomerization of the C=C bond of the allyl unit and subsequent oxidative cleavage of the resulting enamide.     

The N-vinyl group as a protection group of the preparation of 3(5)-substituted pyrazoles via bromine-lithium exchange

Treatment of 3,4,5-tribromopyrazole with 1,2-dibromoethane and triethylamine gave 3,4,5-tribromo-1-vinylpyrazole, which underwent regioselective bromine-lithium exchange at the 5-position. Subsequent addition of an electrophile gave 5-substituted 3,4-dibromo-1-vinylpyrazoles. These underwent bromine-lithium or bromine-magnesium exchange predominantly at the 4-position, with the regioselectivity between the 3- and 4-positions being influenced by the nature of the metal and the 5-substituent. The 5-substituted products were de-vinylated by mild treatment with KMnO₄ affording 3-substituted pyrazoles. Alternatively, the 1-vinyl group could be used in ring-closing metathesis. Thus, 5-allylthio-1-vinylpyrazole produced 5H-pyrazolo[5,1-b][1,3]thiazine upon treatment with Grubbs' second-generation catalyst.     

Syntheses of 4-, 5-, 6-, and 7-substituted tryptamine derivatives and the use of a bromine atom as a protecting group

Orthogonal syntheses of 4-, 5-, 6-, and 7-chloro substituted tryptamine derivatives were performed under the Grandberg–Zuyanova-modified Fisher indole-synthesis conditions. In the 4- and 6-substituted tryptamine cases, a bromine atom was utilized as an easily cleavable protecting group, which allowed complete regiocontrol. In addition, a chlorine substituent was preserved in the debromination step and could be utilized as a synthetic handle for late-stage diversification under modern Pd(0) catalysis conditions.     

Crystal Structure of the Mixed‐Valent Basic Mercury Nitrate HgI2(NO3)2·HgII(OH)(NO3)·HgII(NO3)2·4HgIIO [= Hg8O4(OH)(NO3)5]

Light‐yellow single crystals of the mixed‐valent mercury‐rich basic nitrate Hg₈O₄(OH)(NO₃)₅ were obtained as a by‐product at 85 °C from a melt consisting of stoichiometric amounts of (Hg^I₂)(NO₃)₂·2H₂O and Hg^II(OH)(NO₃). The title compound, represented by the more detailed formula Hg^I₂(NO₃)₂·Hg^II(OH)(NO₃)·Hg^II(NO₃)₂·4Hg^IIO, exhibits a new structure type (monoclinic, C2/c, Z = 4, a = 6.7708(7), b = 11.6692(11), c = 24.492(2) Å, β = 96.851(2)°, 2920 structure factors, 178 parameters, R1[F² > 2σ(F²)] = 0.0316) and is made up of almost linear [O‐Hg^II‐O] and [O‐Hg^I‐Hg^I‐O] building blocks with typical Hg^II‐O distances around 2.06Å and a Hg^I‐O distance of 2.13Å. The Hg₂²⁺ dumbbell exhibits a characteristic Hg‐Hg distance of 2.5079(7) Å. The different types of mercury‐oxygen units form a complex three‐dimensional network exhibiting large cavities which are occupied by the nitrate groups. The NO₃^? anions show only weak interactions between the nitrate oxygen atoms and the mercury atoms which are at distances > 2.6Å from one another. One of the three crystallographically independent nitrate groups is disordered.     

Regioselective splitting of 3-alkyl-1-ethylaluminacyclopentanes with orthoformates as a new route to 1-functionalized 4-methylalkanes

The reactions of triethyl, diethyl phenyl, or tributyl orthoformate with 1,3-dialkylaluminacyclopentanes results in regioselective cleavage of the sterically less hindered Al—C(5) bond; hydrolysis of the reaction mixture gives 4-methyl aldehyde acetals. In the case of more inert orthoformates, the process is activated with catalytic amounts of ZrCl₄.     

From Isolated Polyanions to 1‐D Structure: Synthesis and Crystal Structure of Hybrid Fluorides {[(C2H4NH3)3NH]4+}2 · (H3O)+ · [Al7F30]9– and {[(C2H4NH3)3NH]4+}2 · [Al7F29]8– · (H2O)2

Two new hybrid fluorides, {[(C₂H₄NH₃)₃NH]⁴⁺}₂ · (H₃O)⁺ · [Al₇F₃₀]^9– ( I ) and {[(C₂H₄NH₃)₃NH]⁴⁺}₂ · [Al₇F₂₉]^8– · (H₂O)₂ ( II ), are synthesized by solvothermal method. The structure determinations are performed by single crystal technique. The symmetry of both crystals is triclinic, sp. gr. P 1, I : a = 9.1111(6) Å, b = 10.2652(8) Å, c = 11.3302(8) Å, α = 110.746(7)°, β = 102.02(1)°, γ = 103.035(4)°, V = 915.9(3) ų, Z = 1, R = 0.0489, R_w = 0.0654 for 2659 reflections, II : a = 8.438(2) Å, b = 10.125(2) Å, c = 10.853(4) Å, α = 106.56(2)°, β = 96.48(4)°, γ = 94.02(2)°, V = 877.9(9) ų, Z = 1, R = 0.0327, R_w = 0.0411 for 3185 reflections. In I , seven corner‐sharing AlF₆ octahedra form a [Al₇F₃₀]^9– anion with pseudo 3 symmetry; such units are found in the pyrochlore structure. The aluminum atoms lie at the corners of two tetrahedra, linked by a common vertex. In II , similar heptamers are linked in order to build infinite (Al₇F₂₉)_n^8– chains oriented along a axis. In both compounds, organic moieties are tetra protonated and establish a system of hydrogen bonds N–H…F with four Al₇F₃₀^9– heptamers in I and with three inorganic chains in II .     

Synthesis,Crystal Structure and Magnetic Behaviour of the new Tetrameric Gadolinium Carboxylate [Gd4(OH)4(CF3COO)8(H2O)4] · 2.5 H2O

The novel tetrameric gadolinium(III) compound [Gd₄(OH)₄(CF₃COO)₈(H₂O)₄] · 2.5 H₂O was synthesized and structurally characterized by X‐ray crystallography. The Gd³⁺ ions are bridged by hydroxide ions and carboxylate groups to tetramers with Gd³⁺‐Gd³⁺ distances between 384.2(2) and 388.1(2) pm. The compound crystallizes in the monoclinic space group C2/c (Z = 4). The magnetic behaviour of [Gd₄(OH)₄(CF₃COO)₈(H₂O)₄] · 2.5 H₂O was investigated in the temperature range of 2 to 300 K. The magnetic data of this compound indicate antiferromagnetic interactions (J_ex = ?0.0197 cm^?1).