Trifluoroacetyl as an orthogonal protecting group for guanidines

The trifluoroacetyl moiety has been used as a new protecting group for guanidine functionality. The protecting group is easily cleaved under mild basic conditions and is complementary to the Boc, Cbz, and Ddpe protecting groups. The protecting group can be applied to peptide synthesis in solution as well as on a solid phase as it is orthogonal to a Boc and Cbz strategy and semiorthogonal to an Fmoc strategy.     

Protecting groups in carbohydrate chemistry: influence on stereoselectivity of glycosylations

Saccharides are polyhydroxy compounds, and their synthesis requires complex protecting group manipulations. Protecting groups are usually used to temporarily mask a functional group which may interfere with a certain reaction, but protecting groups in carbohydrate chemistry do more than protecting groups usually do. Particularly, protecting groups can participate in reactions directly or indirectly, thus affecting the stereochemical outcomes, which is important for synthesis of oligosaccharides. Herein we present an overview of recent advances in protecting groups influencing stereoselectivity in glycosylation reactions, including participating protecting groups, and conformation-constraining protecting groups in general.     

Bromine catalyzed conversion of S-tert-butyl groups into versatile and, for self-assembly processes accessible, acetyl-protected thiols

The facile and efficient conversion of a tert-butyl protecting group to an acetyl protecting group for thiols by catalytic amounts of bromine in acetyl chloride and the presence of acetic acid has been developed. The fairly mild reaction conditions are of particular interest for new protecting group strategies for sulfur functionalised target structures.     

醇(酚)羟基的硅烷化保护与去保护研究进展

醇(酚)羟基的硅烷化保护是一类重要的有机合成手段,目的在于使羟基稳定化,消除或减轻其引起的副反应。保护基中硅原子连接的基团空间位阻越小,该保护基的反应活性越大,生成的相应硅醚的稳定性则越差,在弱酸或弱碱的条件下即可脱除;硅原子连接的基团越大,该保护基的反应活性则越小,硅醚化反应越难发生,需要借助催化剂才能进行。本文尽可能全面地论述了有机硅烷保护基的类型,如三甲基硅烷、三乙基硅烷、叔丁基二甲基硅烷、三异丙基硅烷、苯基取代硅烷和桥型硅烷等,并讨论了其在不同环境下的活性及稳定性。     

Protecting-group-based colorimetric monitoring of fluorous-phase and solid-phase synthesis of oligoglucosamines

A new hydroxyl protecting group, nitrophthalimidobutyric (NPB) acid, has been synthesized in one solvent-free step for colorimetric monitoring of reaction cycles upon its facile removal with hydrazine acetate in the solid-phase and fluorous-phase syntheses of antigenic oligoglucosamines associated with infectious Staphylococcus aureus. The NPB group serves as a convenient hydroxyl protecting group that is stable to the basic conditions required for the synthesis of the common trichloroacetimidate protecting groups, the strongly acidic conditions used in glycosylation reactions, as well as conditions commonly used to remove silicon-based protecting groups.     

A fluorous phosphate protecting group with applications to carbohydrate synthesis

The first fluorous protecting group for phosphate is reported. This group can be used as a facile tag for purification and be removed under mild reducing conditions using zinc and ammonium formate. Synthesis of a disaccharide from Leishmania using this fluorous protecting group demonstrated the group's stability to the acidic conditions necessary for glycosylation as well as its orthogonality to several other common protecting groups.     

Application of the NG-(2,2,5,7,8-pentamethylchroman-6-sulphonyl) derivative of FMOC-arginine to peptide synthesis

The trifluoroacetic acid labile pentamethylchromanylsulphonyl protecting group for the guanidino group of arginine has been used in conjunction with the base-labile Fmoc Nα protecting group for the synthesis of arginine-containing peptides.     

A comprehensive approach to the synthesis of sulfate esters

A comprehensive approach to the synthesis of sulfate esters was developed. This approach permits the direct and high-yielding synthesis of protected sulfate monoesters. Subsequent deblocking to reveal sulfate monoesters is accomplished in near-quantitative yield. The exceptionally stable neopentyl protecting group and the labile isobutyl protecting group were utilized in the synthesis of aromatic and aliphatic sulfate monoesters. Strategies for tuning protecting group reactivity were also explored and developed.     

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.     

5-Chloro-8-quinolyl group as high efficient phosphate protecting group for the synthesis of oligoribonucleotides

5-Chloro-8-quinolyl group is found to be very suitable for the protecting group on phosphates in the internucleotidic bonds. The oligoribonucleotides were obtained in good yields by a simple procedure using this phosphate protecting group.     

The tertiary-butyl group: Selective protection of the anomeric centre and evaluation of its orthogonal cleavage

The tertiary-butyl group has not been examined extensively as a protecting group. In this work, we describe the synthesis of tert-butyl glycosides via the Fischer glycosylation protocol. Furthermore, its utility as a temporary anomeric protecting group was evaluated. A range of differentially protected monosaccharides was used to investigate the stability of the tert-butyl group upon the introduction of other protecting groups; and compatibility of its cleavage in the presence of the latter.     

烯丙基保护基在多羟基化合物中的应用

烯丙基保护基由于能够在温和的反应条件下,在羟基、氨基等基团中引入和脱除,并且具有很好的区域选择性和化学选择性,因此被广泛应用于有机合成中。本文介绍了烯丙基保护基的发展历史,综述了烯丙保护基对多羟基化合物中不同羟基的选择性保护应用,并阐述了烯丙保护基的引入和脱除的机理及方法。     

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.     

A formal total synthesis of (+/-)-neplanocin A

Stereoselective formal synthesis of (+/-)-neplanocin A from a cyclopentane derivative employing an elegant strategy involving reiterative usage of an already existing acetonide protecting group is reported. The acetonide protecting group that is carried forward intact right from the starting adduct to an advanced intermediate is shuffled around twice as in a "relay race" through the synthetic sequence, thus avoiding unnecessary employment of additional protecting groups.     

Advances in Protecting Groups for Oligosaccharide Synthesis

Carbohydrates contain numerous hydroxyl groups and sometimes amine functionalities which lead to a variety of complex structures. In order to discriminate each hydroxyl group for the synthesis of complex oligosaccharides, protecting group manipulations are essential. Although the primary role of a protecting group is to temporarily mask a particular hydroxyl/amino group, it plays a greater role in tuning the reactivity of coupling partners as well as regioselectivity and stereoselectivity of glycosylations. Several protecting groups offer anchimeric assistance in glycosylation. They also alter the solubility of substrates and thereby influence the reaction outcome. Since oligosaccharides comprise branched structures, the glycosyl donors and acceptors need to be protected with orthogonal protected groups that can be selectively removed one at a time without affecting other groups. This minireview is therefore intended to provide a discussion on new protecting groups for amino and hydroxyl groups, which have been introduced over last ten years in the field of carbohydrate synthesis. These protecting groups are also useful for synthesizing non‐carbohydrate target molecules as well.     

Chemical synthesis of RNA via 2′-O-cyanoethylated intermediates

It was found that 2′-O-cyanoethyl group could be removed from 2′-O-cyanoethylated ribonucleoside derivatives by treatment with Bu₄NF. This finding was successfully applied to the synthesis of oligoribonucleotides via their 2′-O-cyanoethylated derivatives as key intermediates where a cyanoethyl group was used as the 2′-hydroxyl protecting group. The rate of condensation using this protecting group in the presence of various activators was generally faster than that observed when a TBDMS group was used as the protecting group.     

A new safety-catch protecting group and linker for solid-phase synthesis

The use of two derivatives of 2-methoxy-4-methylsulfinylbenzyl alcohol is demonstrated as a safety-catch protecting group and linker for solid-phase peptide synthesis. The protecting group and linker are stable to TFA and are readily removed under reductive acidolytic conditions.     

π-Picclhtyi,Group as a New Audio Propeocting Group for Peptide Synthesis

Previous work has suggested that metal ion sensitive protecting groups may have utility in organic synthesis⁽¹⁾. We report hore the use of the α -picolinyl group as an amino protecting group for peptide synthesis.     

Linear synthesis of a protected H-type II pentasaccharide using glycosyl phosphate building blocks.

A linear synthesis of a fully protected H-type II blood group determinant pentasaccharide utilizing glycosyl phosphate and glycosyl trichloroacetimidate building blocks is reported. Envisioning an automated solid-phase synthesis of blood group determinants, the utility of glycosyl phosphates in the stepwise construction of complex oligosaccharides, such as the H-type II antigen, is demonstrated. Installation of the central glucosamine building block required the screening of a variety of nitrogen protecting groups to ensure good glucosamine donor reactivity and protecting group compatibility. The challenge to differentiate C2 of the terminal galactose in the presence of other hydroxyl and amine protecting groups prompted us to introduce the 2-(azidomethyl)benzoyl group as a novel mode of protection for carbohydrate synthesis. The compatibility of this group with traditionally employed protecting groups was examined, as well as its use as a C2 stereodirecting group in glycosylations. The application of the 2-(azidomethyl)benzoyl group along with a systematic evaluation of glycosyl donors allowed for the completion of the pentasaccharide and provides a synthetic strategy that is expected to be generally amenable to the solid support synthesis of blood group determinants.     

1-naphthylpropargyl ether group: a readily cleaved and sterically minimal protecting system for stereoselective glycosylation

[reaction: see text] The (1-naphthyl)propargyl group is introduced as a sterically unobtrusive alcohol protecting group that is cleaved in a single step by exposure to dichlorodicyanoquinone in wet dichloromethane. In conjunction with the 4,6-O-benzylidene protecting group, and the use of the sulfoxide glycosylation method, 3-O-naphthylpropargyl-protected mannosyl donors are extremely beta-selective.