Total synthesis of cucurbitoside A using a novel fluorous protecting group

The first total synthesis of cucurbitoside A was achieved using a new fluorous N-phenylcarbamoyl (^FCar) protecting group. The ^FCar group was introduced into carbohydrates in high yield and was selectively removed with Bu₄NNO₂ without damaging other acyl protecting groups. The synthetic intermediates were easily isolated by fluorous solid-phase extraction.     

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.     

A convenient method for the synthesis of N-hydroxyureas

Treatment of amines with 1-(4-nitrophenol)-N-(O-benzylhydroxy)carbamate yields the O-benzyl protected N-hydroxyureas. Hydrogenation of the O-benzyl protected N-hydroxyureas over 5% Pd/BaSO₄ cleanly gives the N-hydroxyureas in good yield. In addition to primary and secondary aliphatic and aromatic amines, this method converts amino sugars to the corresponding N-hydroxyureas without extensive protecting group chemistry.     

N-substitution of polybenzimidazoles: Synthesis and evaluation of physical properties

Series of N-substituted polybenzimidazoles (PBI) were synthesized using selective alkyl groups with varying bulk and flexibility, viz., methyl, n-butyl, methylene trimethylsilane and 4-tert-butylbenzyl. PBI-I based on 3,3′-diaminobenzidine (DAB) and isophthalic acid and PBI-BuI based on DAB and 5-tert-butyl isophthalic acid were chosen for N-substitution. Structural characterizations of substituted polymers by FT-IR and ¹H NMR revealed elimination of hydrogen bonding. Evaluation of their physical properties revealed that N-substitution rendered better solvent solubility in common organic solvents, more open polymer matrix, but reduced thermal properties in comparison to their respective parent PBI. 4-tert-butylbenzyl, methylene trimethylsilane or n-butyl group substituted polymers were soluble even in chlorinated solvents (CHCl₃ and TCE). Substantial variations in gas permeability of inert gases, He and Ar and attractive P_He/P_Ar selectivity, especially after methyl group substitution depicted potential of these materials for gas separation.     

Synthesis of dinucleoside phosphates and their analogs by the boranophosphotriester method using azido-based protecting groups

Oligodeoxyribonucleotides and their backbone-modified analogs were synthesized in good yields by the boranophosphotriester method in solution. The oligodeoxyriobonucleoside boranophosphates, fully protected with 2-(azidomethyl)benzoyl groups, were converted to the various backbone-modified DNA analogs via the corresponding H-phosphonate intermediates. A new efficient protecting group for the O⁶-position of 2′-deoxyguanosine, 4-[(2-azidomethyl)benzoyloxy]benzyl (AZBn) group, was also developed. The AZBn group was found to be quickly removed by treatment with MePPh₂ in dioxane-2-mercaptoethanol-H₂O.     

Cleavage of alkoxycarbonyl protecting groups from carbamates by t-BuNH2

An efficient, simple protocol for the selective cleavage of a variety of N-alkoxycarbonyl protecting groups by t-BuNH₂/MeOH is described. The scope of the procedure was explored for a series of indole, aniline and pyrrolidine carbamate derivatives containing other potentially reactive functional groups affording a clean cleavage of the carbamate group.     

Selective deprotection and amidation of 2-pyridyl esters via N-methylation

The 2-pyridyl residue serves as a protecting group for various carboxylic acids. The protecting group is selectively cleaved under mild conditions via N-methylation of the pyridyl group. During the deprotection process, the various functional groups as well as the other ester moieties remain intact. The N-methylated active esters can be subsequently transformed into amides.     

Synthesis of the sphingolipid activator protein, saposin C, using an azido-protected O-acyl isopeptide as an aggregation-disrupting element

In order to achieve an efficient synthesis of highly hydrophobic proteins by the native chemical ligation (NCL) reaction, we examined to incorporate the O-acyl isopeptide method, which is known to improve the solubility of the segment, to the NCL reaction: a peptide thioester having O-acyl isopeptide structures is prepared by the Boc mode solid-phase method using an azido group as a protecting group for the isopeptide site, and then ligated with C-terminal segment with an in situ reduction of the azido group followed by an O- to N-acyl shift. This method was successfully applied to the synthesis of the sphingolipid activator protein, saposin C.     

The use of 2-O-propagyloxycarbonyl protecting group in the selective formation of 1,2-trans-glycosidic linkage

The effect of N-phenylcarbamoyl (Car) and propagyloxycarbonyl (Poc) protecting groups at the O-2 position of donors was examined. The usefulness of Poc group in the selective formation of 1,2-trans-glycosidic linkage is shown by comparing the reactivity of donors having Car or acyl (Bz) groups.     

Synthesis of N,N-Ac,Boc laurylthio sialoside and its application to O-sialylation

The combination of the 5-N-tert-butoxycarbonyl (Boc) group of laurylthio sialoside and cyclopentyl methyl ether (CPME) as a solvent enhanced the reactivity and α-selectivity of the sialyl donor during sialylation. Selective deprotection of the N-Boc group of sialoside, including an acid-sensitive isopropylidene function, was successfully achieved by Yb(OTf)₃-SiO₂. Transformation of N,N-Ac,Boc into an N-acetylglycolyl group of sialoglycoside was easily performed via selective N-deacylation of the mixed Ac-N-Boc carbamate, subsequent Boc group removal, and acylation.     

Selective O-acylation of unprotected N-benzylserine methyl ester and O,N-acyl transfer in the formation of cyclo[Asp-Ser] diketopiperazines

The synthesis of two diastereomeric cyclo[Asp-N-Bn-Ser] diketopiperazines (2a and 2b) was investigated. Initial formation of the Boc-aspartyl-N-benzyl serine isopeptide methyl esters (4a and 4b) was observed, which derive from the selective O-acylation of unprotected (S)- or (R)-N-benzylserine. This unexpected O-acylation is preferred over the formation of the tertiary amide and the resulting ester bond is stable in solution to O,N-acyl transfer. The O,N-acyl migration is then triggered by cleavage of the Boc protecting group and treatment with base, which also promotes immediate cyclization to the diketopiperazines.     

4-Methoxybenzyloxymethyl group as an N-protecting group for histidine to eliminate side-chain-induced racemization in the Fmoc strategy

The 4-methoxybenzyloxymethyl (MBom) group was introduced at the N^π-position of histidine, and its utility was examined under the conditions for peptide synthesis by Fmoc strategy. The N^π-MBom group proved to prevent the risk of racemization during incorporation of the His residue and to possess all of the chemical properties required for Fmoc chemistry. The side reaction associated with formaldehyde generated from the N^π-MBom group upon acidolysis could be effectively prevented by performing the standard TFA treatment in the presence of methoxyamine·hydrochloride (MeONH₂·HCl).     

Chemoselective protection of thiols versus alcohols and phenols. The Tosvinyl group

The conjugate addition of aliphatic and aromatic thiols to ethynyl p-tolyl sulphone (tosylacetylene) has been managed to afford Tosvinyl derivatives chemoselectively (in the presence of oxygen nucleophiles) and stereoselectively (isomers Z) in practically quantitative yields. The conditions of choice are: catalytic amounts of Et₃N (only 0.5-1.0 mol%), a reaction temperature around 0°C and, for the less acidic thiols, CF₃CH₂OH or CH₃CN/CF₃CH₂OH as the solvent. Thus, N-Boc-Cys-OMe has been quantitatively protected as its S-Tosvinyl derivative in the presence of N-Boc-Ser-OMe and N-Boc-Tyr-OMe. This novel protecting group is stable to several basic and acidic conditions; its removal is achieved at rt by treatment with an excess of pyrrolidine or at 0°C with alkanethiolate ions.     

Protecting group migration in the chemistry of 1-t-butyldimethylsilyl-4-hydroxymethyl-2-azetidinone

The alkoxide anion derived from 1-t-butyldimethylsilyl-4-hydroxymethyl-2-azetidinone (1) rearranged at −78°C into amide anion by N-O migration of the silyl protecting group. The occurrence of this intermediate was proved by quenching with benzyl bromide and phenethyl chloroformate, giving respectively N-benzyl (4) and N-(phenethyloxycarbonyl) (6) derivatives of 4-(t-butyldimethylsilyloxy)methyl-2-azetidinone.     

A general method for the asymmetric synthesis of both enantiomers of 1-substituted 1,2,3,4-tetrahydro-β-carbolines employing pyroglutamic acid derivatives as chiral auxiliaries

9-(S)-Pyroglutaminyl-β-carbolines were allowed to react with a nucleophile (allyltributyltin or a silyl enol ether) in the presence of 2,2,2-trichloroethyl chloroformate to give 1,2-addition products in good yields and high diastereoselectivity. The chiral auxiliary at N-9 was readily removed by a mild hydrolysis. The same chiral source afforded both enantiomers by simply altering a protecting group of the amide nitrogen. That is, (S)-pyroglutaminyl groups which had an N-alkyl group afforded the (S) isomer, whereas the ones having an N-acyl group produced the (R) isomer of the addition products.     

Degradation of trichloroethylene in aqueous solution by persulfate activated with Fe(III)–EDDS complex

In this study, an environmentally friendly complexing agent, S,S′-ethylenediamine-N,N′-disuccinic acid (EDDS), was applied in Fe(III)-mediated activation of persulfate (PS), and the degradation performance of trichloroethylene (TCE) was investigated. The effects of PS concentration, Fe(III)/EDDS molar ratio, and inorganic anions on TCE degradation were evaluated, and the generated reactive oxygen species responsible for TCE removal were identified. The results showed that nearly complete TCE degradation was achieved with PS of 15.0 mM and a molar ratio of Fe(III)/EDDS of 4:1. An increase in PS concentration or Fe(III)/EDDS molar ratio to a certain value resulted in enhanced TCE degradation. All of the anions (Cl^?, HCO₃ ^?, SO₄ ^2?, and NO ₃ ^? ) at tested concentrations had negative effects on TCE removal. In addition, investigations using radical probe compounds and radical scavengers revealed that sulfate radicals (SO ₄ ^·? ), hydroxyl radicals (^·OH), and superoxide radical anions (O ₂ ^·? ) were all generated in the Fe(III)–EDDS/PS system, and ^·OH was the primary radical responsible for TCE degradation. In conclusion, the Fe(III)–EDDS-activated PS process is a promising technique for TCE-contaminated groundwater remediation.     

A facile synthesis of 2-(N-alkylamino)-pyrimidin-4-one derivatives

Substituted 2-(N-alkylamino)-pyrimidin-4-ones were synthesized from N-alkyl β-amino acid esters starting with guanidinylation using Pbf-activated thiourea. The six-membered pyrimidinones were obtained in good yields via intramolecular cyclization during TFA cleavage of the Pbf protecting group.     

Biodegradation analyses of trichloroethylene (TCE) by bacteria and its use for biosensing of TCE

Trichloroethylene (TCE) is a toxic, recalcitrant groundwater pollutant. TCE-degrading microorganisms were isolated from various environments. The aerobic bacteria isolated from toluene- and tryptophan-containing media were Pseudomonas sp. strain ASA86 and Burkholderia sp. strain TAM17, respectively; these are necessary for inducing TCE biodegradation in a selective medium. The half-degradation time of TCE to a concentration of 1 mg/L was 18 h for strain ASA86 and 7 days for strain TAM17. While identifying toluene/TCE degradation genes, we found that in strain ASA86, the gene was the same as the todC1 gene product encoding toluene dioxygenase identified in Pseudomonas putida F1, and that in strain TAM17, the gene was similar to the tecA1 gene product encoding chlorobenzene dioxygenase identified in Burkholderia sp. PS12. A novel TCE biosensor was developed using strain ASA86 as the inducer of toluene under aerobic conditions. The TCE biosensor exhibited a linear relationship below 3 ppm TCE. Detection limit of the biosensor was 0.05 ppm TCE. The response time of the biosensor was less than 10 min. The biosensor response displayed a constant level during a 2 day period. The TCE biosensor displayed sufficient sensitivity for monitoring TCE in environmental systems.     

Synthesis of photolabile o-nitroveratryloxycarbonyl (NVOC) protected peptide nucleic acid monomers

The chemical synthesis of peptide nucleic acid (PNA) monomers was accomplished using various combinations of the o-nitroveratryloxycarbonyl (NVOC) group (N-aminoethylglycine backbone) and base labile acyl-type nucleobase protecting groups (anisoyl for adenine and cytosine; isobutyryl for guanine), thus offering a photolithographic solid-phase PNA synthetic strategy compatible with photolithographic oligonucleotide synthesis conditions and allowing the in situ synthesis of PNA microarrays in an essentially neutral medium, by avoiding the use of the commonly used deprotection reagents such as trifluoroacetic acid or piperidine. Convenient methods were also explored to prepare 1-(carboxymethyl)-4-N-(4-methoxybenzoyl)cytosine and 9-(carboxymethyl)-2-N-(isobutyryl)guanine with good yields.     

A practical approach to non-natural or N-unsubstituted α-arylglycine derivatives: Hf(OTf)4-doped Me3SiCl system-catalyzed aminomethylation of electron-rich arenes with a new type of N,O-acetal

The authors have demonstrated the Hf(OTf)₄-doped Me₃SiCl system-catalyzed aminomethylation of electron-rich aromatic compounds, such as indoles and anilines, with new types of N,O-acetals having a variety of functional groups, such as cyano, ester, bis(trimethylsilyl)amino, diallylamino, and cyclic amino moieties, for the preparation of non-natural aromatic amino acid derivatives. Aminomethylation using an N,O-acetal with a bis(trimethylsilyl)amino group was particularly successful in the direct preparation of an N-unsubstituted α-indolylglycine derivative, which required only a standard aqueous workup.