2-(4-Tolylsulfonyl)ethoxymethyl (TEM)-a new 2'-OH protecting group for solid-supported RNA synthesis

The 2-(4-tolylsulfonyl)ethoxymethyl (TEM) as a new 2'-OH protecting group is reported for solid-supported RNA synthesis using phosphoramidite chemistry. The usefulness of the 2'-O-TEM group is exemplified by the synthesis of 12 different oligo-RNAs of various sizes (14-38 nucleotides long). The stepwise coupling yield varied from 97-99% with an optimized coupling time of 120 s. The synthesis of all four pure phosphoramidite building blocks is also described. Two new reliable parameters, delta(C2')-delta(C3') and delta(H2')-delta(H3'), have been suggested for the characterization of isomeric 2'-O-TEM and 3'-O-TEM as well as other isomeric mono 2'/3'-protected ribonucleoside derivatives. The most striking feature of this strategy is that the crude RNA prepared using our 2'-O-TEM strategy is sufficiently pure (>90%) for molecular biology research without any additional purification step, thereby making oligo-RNAs easily available at a relatively low cost, saving both time and lab resources.     

2-(Prenyloxymethyl)benzoyl (POMB) group: a new temporary protecting group removable by intramolecular cyclization

2-(Prenyloxymethyl)benzoates can be prepared from alcohols and readily available 2-(prenyloxymethyl)benzoic acid by standard acylation techniques or by Mitsunobu reaction with inversion of configuration. The POMB group can be cleaved first by oxidative removal of the prenyl group with DDQ followed by lactonization with expulsion of the alcohol catalyzed by Yb(OTf)₃. These reaction conditions are compatible with the presence of a large number of common protecting groups.     

2-(2-pyridyl-)ethyl esters A new carboxyl protecting group in peptide synthesis

2-(2-pyridyl-)ethyl esters are used as chemically inert, highly selective protecting groups that are removable under mild conditions via a two step procedure.     

2-(Prenyloxymethyl)benzoyl (POMB) as a new temporary protecting group for alcohols

The 2-(prenyloxymethyl)benzoyl (POMB) group was introduced in high yields to hydroxyl functions using the crystalline reagent, 2-(prenyloxymethyl)benzoic acid, in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). 2-(Prenyloxymethyl)benzoic acid is readily available, in two steps, from phthalide in 65% overall yield. The POMB group can be cleaved, in two steps, by treatment with 2,3-dichloro-5,6-dicyanoquinone (DDQ) followed by intramolecular lactonisation of the resulting hydroxy ester induced by a catalytic amount of Yb(OTf)₃·H₂O. The reaction conditions are compatible with the presence of a number of protecting groups such as isopropylidene, benzyl, acetyl, chloroacetyl, benzoyl, levulinoyl, Fmoc and Boc groups.     

Anthraquinon-2-ylmethoxycarbonyl (Aqmoc): a new photochemically removable protecting group for alcohols

[see structure]. Synthesis and photochemistry of a new photochemically removable protecting group for alcohols is described. Four carbonates of galactose derivatives (1-4) were synthesized from the corresponding arylmethanols via 4-nitrophenyl carbonate intermediates. Among them, photolysis of anthraquinon-2-ylmethoxycarbonyl (Aqmoc) galactose (1) proceeded with overall photolysis efficiency of 150 (quantum yield 0.10, and molar absorptivity 1500 M(-1) x cm(-1)) and rate constant of approximately 10(6) s(-1). To demonstrate its application to a biologically related molecule, 5'-Aqmoc-adenosine (5) was synthesized and photolyzed to yield adenosine in 91% yield.     

2-(1,3-Dioxan-2-yl)ethylsulfonyl group: a new versatile protecting and activating group for amine synthesis

[reaction: see text] 2-(1,3-Dioxan-2-yl)ethylsulfonyl (Dios) chloride was synthesized and used as a new versatile sulfonating agent for amines. Primary and secondary amines were sulfonated very easily in excellent yields with Dios chloride. N-Nonsubstituted and N-monosubstituted Dios-amides, activated amines, were alkylated satisfactorily under new Mitsunobu conditions utilizing (cyanomethylene)tributylphosphorane (CMBP). The Dios group is very stable under basic and reductive conditions and is removed by heating in a hot aqueous solution of trifluoroacetic acid.     

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.     

The (1-methyl)cyclopropyloxycarbonyl (MPoc) carbamate: a new protecting group for amines

The (1-methyl)cyclopropyl carbamate (MPoc) group represents a new and useful protecting group for amines. It adds relatively little molecular weight and has a simple ¹H NMR spectrum. It is orthogonal to the commonly used BOC, Cbz, Alloc, and FMOC groups. MPoc protected amines are resistant to extremes of pH, amines, halogens, many oxidizing agents, and to hydrogenation at ambient temperature. The MPoc group is cleaved by exposure to hypobromous acid or upon hydrogenolysis over palladium at 80 °C.     

2-diphenylmethylsilylethyl group as a new protecting group of internucleotidic phosphates in oligonucleotide synthesis

Internucleotidic phosphates were protected by 2-diphenylmethylsilylethyl which was selectively removed by treatment with tetrabutylammonium fluoride.     

A new photochemically removable protecting group for amines

A new arylmethylsulfonyl chloride reacts with secondary or primary amines to give sulfonamides which can be photochemically cleaved, making it suitable for use as a photoremovable protecting group.     

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.     

1-[2-(2-hydroxyalkyl)phenyl]ethanone: a new photoremovable protecting group for carboxylic acids

[reaction: see text] A new photoremovable protecting group for carboxylic acids is introduced. The protecting group 1-[2-(2-hydroxyalkyl)phenyl]ethanone, HAPE, is used to protect various carboxylic acids. When photolyzed, the protected compound releases the acid in 70-85% isolated yields. The synthesis and the results of photorelease of the protected acids are presented here.     

A new oligosaccharide synthesis using special hydroxy protecting group

A new hydroxy protecting group for convenient preparation of oligosaccharide was developed using uni-chemo protection (UCP) concept. The UCP group was comprised of polymerized amino acid derivatives and protecting each hydroxyl groups by ester linkage. Depending on the polymerization degree, the hydroxyl groups were characterized and controlled. Using this protecting group, two kinds of sialyl-T analogues were successfully synthesized from same sugar parts merely by repeating Edman degradation and coupling.     

Base mediated deprotection strategies for trifluoroethyl (TFE) ethers,a new alcohol protecting group

A trifluoroethyl (TFE) ether is specifically introduced as a protecting group in organic chemistry. Its first strategic application and removal in the total synthesis of vinigrol is discussed. Two lithium base mediated deprotection strategies for its removal are presented in this Letter. In one deprotection approach, the trifluoroethyl ether is converted to a difluorovinyl ether and then catalytically cleaved using osmium tetraoxide, while in the second approach a difluorovinyl anion is formed and trapped with an electrophilic oxygen reagent (MoOPH) to form a labile difluoroacetate. To further aid the reader, a summary of approaches for forming trifluoroethyl ethers is included as well as a discussion of alternate deprotection strategies.     

2-Arylallyl as a new protecting group for amines, amides and alcohols

Amines, amides and ethers containing 2-arylallyl groups are selectively and easily deprotected with tert-butyllithium. This transformation probably involves a carbolithiation reaction of the styrenyl moiety followed by a beta-elimination process.     

The 2-(methylthiomethoxy)ethoxycarbonyl [mtmec] protecting group

Alcohols (ROH) may be converted into their MTMEC derivatives ($\text{6}$) by acylation with 2-(methylthiomethoxy)ethoxycarbonyl chloride ($\text{5}$); the MTMEC “protected protecting group” may be removed by treatment first with Hg(II) perchlorate in the presence of 2,4,6-collidine or pyridine in acetone-water solution, followed by hydrolysis under very mild basic conditions.     

Epoc group: transformable protecting group with gold(iii)-catalyzed fluorene formation

This study presents the novel concept of a transformable protecting group, which changes its properties through structural transformation. Based on this concept, we developed a 2-(2-ethynylphenyl)-2-(5-methylfuran-2-yl)-ethoxycarbonyl (Epoc) group. The Epoc group was transformed into an Fmoc-like structure with gold(iii)-catalyzed fluorene formation and was removable under Fmoc-like mild basic conditions post-transformation even though it was originally stable under strongly basic conditions. As an application for organic synthesis, the Epoc group provides the novel orthogonality of gold(iii)-labile protecting groups in solid-phase peptide synthesis. In addition, the high turnover number of fluorene formation in aqueous media is suggestive of the applicability of the Epoc group to biological systems.

A protecting group removable with gold(iii)-catalyzed fluorene formation and the subsequent addition of piperidine was developed.     

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.