Polymeric Protecting Groups. 6. Synthesis of a Novel N-Ethenoxyamino-Modified tert-Butoxycarbonyl-Type Amino Protecting Group

1994 ◽  
Vol 27 (18) ◽  
pp. 5227-5228 ◽  
Author(s):  
Marcus Gormanns ◽  
Helmut Ritter
Keyword(s):  
Protecting Groups ◽  
Protecting Group

Protecting Groups

2008 ◽  
Author(s):  
Jie Jack Li ◽  
Chris Limberakis ◽  
Derek A. Pflum
Keyword(s):  
Low Temperature ◽  
Organic Synthesis ◽  
Secondary Alcohol ◽  
Primary Alcohol ◽  
Protecting Groups ◽  
Silyl Ether ◽  
Benzyl Ether ◽  
Protecting Group ◽  
Selective Protection ◽  
Death Taxes

In his book, Protecting Groups, Philip J. Kocieński stated that there are three things that cannot be avoided: death, taxes, and protecting groups. Indeed, protecting groups mask functionality that would otherwise be compromised or interfere with a given reaction, making them a necessity in organic synthesis. In this chapter, for each protecting group showcased, only the most widely used methods for protection and cleavage are shown. Also, this section is not comprehensive and only addresses some of the most common blocking groups in organic synthesis. For a thorough review of protecting groups, the reader should consult the following references: (a) Wuts, P. G. M.; Greene, T. W.; Protective Groups in Organic Synthesis, 4th ed.; Wiley: Hoboken, NJ, 2007; (b) Kocienski, P. J. Protecting Groups, 3rd edition.; Thieme: Stuggart, 2004. In this section, the formation and cleavage of eight protecting groups for alcohols and phenols are presented: acetate; acetonides for diols; benzyl ether; para-methoxybenzyl (PMB) ether; methyl ether; methoxymethylene (MOM) ether; tert-butyldiphenylsilyl (TBDPS) silyl ether; and tetrahydropyran (THP). Acetate is a convenient protecting group for alcohols—easy on and easy off. Selective protection of a primary alcohol in the presence of a secondary alcohol can be achieved at low temperature. The drawback of this protecting group is its incompatibility with hydrolysis and reductive conditions.

Protecting-group-free synthesis of haterumadienone- and puupehenone-type marine natural products

2017 ◽  
Vol 19 (9) ◽  
pp. 2140-2144 ◽  
Author(s):  
Hong-Shuang Wang ◽  
Hui-Jing Li ◽  
Jun-Li Wang ◽  
Yan-Chao Wu
Keyword(s):  
Natural Products ◽  
Transition Metals ◽  
Marine Natural Products ◽  
Protecting Groups ◽  
Protecting Group

The atom- and step-economical synthesis of seven puupehenone- and haterumadienone-type marine natural products without the use of protecting groups and transition metals has been achieved from the abundant feedstock chemical sclareolide in only 6 to 9 steps.

Protecting-Group-Directed Regio- and Stereoselective Oxymercuration–Demercuration: Synthesis of Piperidine Alkaloids Containing 1,2- and 1,3-Amino Alcohol Units

Synthesis ◽  
2017 ◽  
Vol 50 (05) ◽  
pp. 1113-1122 ◽  
Author(s):  
Santosh Tilve ◽  
Sandesh Bugde ◽  
Prajesh S.Volvoikar
Keyword(s):  
Amino Alcohol ◽  
Protecting Groups ◽  
Protecting Group ◽  
Efficient Synthesis ◽  
Piperidine Alkaloids ◽  
Naturally Occurring ◽  
Pipecolinic Acid

An efficient synthesis of naturally occurring 1,2- and 1,3-amino alcohol unit containing 2-substituted piperidine alkaloids and their analogues has been developed from l-pipecolinic acid. The protocol describes the regio- and stereoselective oxymercuration–demercuration of 2-alkenyl piperidines based on protecting groups to give piperidine alkaloids as a key step.

scholarly journals The Synthesis of Carbohydrates for the Treatment of Disease

2021 ◽  
Author(s):  
◽  
Emma Marie Dangerfield
Keyword(s):  
Cell Activity ◽  
Protecting Groups ◽  
Inkt Cell ◽  
Primary Amines ◽  
Alamar Blue ◽  
Glycosidase Inhibitors ◽  
Protecting Group ◽  
Comparable Activity ◽  
Species Specific ◽  
Reduced Activity

<p>In this thesis I investigated two aspects of glycobiology. In the first, I investigated the potential of α-GalCer analogues to be used in cancer immunotherapy. Two 4-deoxy α-GalCer analogues, with either a sphinganine or a sphingosine base, were synthesised using a convergent strategy. The α-GalCer sphinganine derivative was synthesised in 14 steps from D-arabinose, and in an overall 13% yield. The α-GalCer sphingosine analogue was synthesised in 13 steps also in 13% yield. Biological analysis revealed that both 4-deoxy analogues possessed comparable activity to α-GalCer in mice, however demonstrated significantly reduced hNKT cell activity. The reduced activity was attributed to species-specific differences in iNKT cell glycolipid recognition rather than reduced CD1d presentation. From these results we suggest that glycolipids developed for potent CD1d-iNKT cell activity in humans should contain a ceramide base with the 4-hydroxyl present. The second part of this thesis focused on protecting group free methodology for the synthesis of sugar mimetics that have proven potential as glycosidase inhibitors. In this work I developed an efficient, high yielding and diastereoselective strategy for the synthesis of a number of five and six membered azasugars. This strategy utilises two novel reaction methodologies. The first enabled the stereoselective formation of cyclic carbamates from olefinic amines, the transition states controlling the stereoselectivity during this reaction are discussed. The second reaction facilitated the synthesis of primary amines without the need for protecting groups, the scope of this reductive amination methodology is also investigated. The five membered azasugars 1,4-dideoxy-1,4-imino-Dxylitol, 1,4-dideoxy-1,4-imino-L-lyxitol, 1,4-dideoxy-1,4-imino-L-xylitol and 1,2,4-trideoxy-1,4-imino-L-xylitol were prepared in 5 steps, in good overall yields (57%, 55%, 54% and 48% respectively), and without the need for protecting groups. The six membered azasugar DGJ was prepared over six steps in 33% yield using similar methodology. The synthesised compounds were also tested for anti-tubercular activity using a BCG alamar blue assay.</p>

scholarly journals Oligonucleotide synthesis using the 2-(levulinyloxymethyl)-5-nitrobenzoyl group for the 5'-position of nucleoside 3'-phosphoramidite derivatives.

1998 ◽  
Vol 45 (4) ◽  
pp. 949-976 ◽  
Author(s):  
K Kamaike ◽  
H Takahashi ◽  
K Morohoshi ◽  
N Kataoka ◽  
T Kakinuma ◽  
...  
Keyword(s):  
Comparative Study ◽  
Protecting Groups ◽  
Protecting Group ◽  
Oligonucleotide Synthesis ◽  
Amino Groups ◽  
Initiator Trna ◽  
15N Labeling

A comparative study on the utility of 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) and 2-(levulinyloxymethyl)benzoyl (LMBz) protecting groups for the 5'-positions of nucleoside 3'-phosphoramidite derivatives in the oligonucleotide synthesis is presented in terms of the syntheses of TpTpT, TpTpTpT, and UpCpApGpUpUpGpG. In addition we describe the synthesis, using the LMNBz protecting group, of the CpCpA terminus triplet of tRNAs bearing exocyclic amino groups with 15N-labeling, and the trimer Gp[A*]pG containing 2'-O-(beta-D-ribofuranosyl)adenosine ([A*]), the latter of which is found at position 64 in the yeast initiator tRNA(Met).

scholarly journals Azulene-based Protecting Groups

2021 ◽  
Author(s):  
◽  
Thomas Bevan
Keyword(s):  
Carboxylic Acids ◽  
Uv Light ◽  
Colour Change ◽  
Protecting Groups ◽  
Small Scale ◽  
Synthetic Chemistry ◽  
Coupling Reactions ◽  
Protecting Group ◽  
Complex Target ◽  
Routine Handling

<p>Protecting groups form an indispensable part of modern organic synthetic chemistry. Besides the benefits of selectively passivating certain reactive functionalities, they often provide handling benefits – such as a decrease in the polarity of the compound that facilitates purification, an increase in the structural order of a compound that allows for easier crystallisation, and chromophores that enable easy visualisation on fluorescent TLC plates under UV light.  Coloured protecting groups offer additional advantages in synthetic chemistry. They expedite purification by allowing the material to be tracked visually. Phase separation and column chromatography are easier to perform, and reduce the need for the collection of large numbers of fractions, while small-scale loss of material (left behind on taps or in flasks during routine handling) and spillages are much more readily apparent. Despite these advantages, only a few coloured protecting groups have been reported in the literature.  The azulenes are a class of compounds with several attractive qualities that can be exploited for use as protecting groups. They are coloured, but not overwhelmingly so. The colour is tunable through placement of electron-donating or electron-withdrawing groups at positions on the ring system, which further allows for protection/deprotection reactions to be designed that incorporate a colour change. Azulene itself is both non-polar and structurally compact, unlike many other organic chromophores such as triarylmethane dyes and carotenoids. Furthermore, azulene’s ability to stabilise both positive and negative charges through resonance with tropylium and cyclopentadienide motifs allows for unusual chemistry, and therefore potentially orthogonal modes of deprotection.  Four protecting group candidates incorporating azulene were devised. The 1-azulenylmethylene amine 79 and the 1-azulenesulfonamide 82 protecting group candidates for amines had fatal flaws that were discovered early, such as a tendency to rapidly degrade in open air. The 1-azulenecarboxylate protecting group candidate 74 for alcohols showed some promise, with a high-yielding protection reaction, but none of the deprotection conditions that were developed were sufficiently mild to be usable in a late-stage deprotection strategy on a complex target molecule.  The final protecting group candidate, 6-(2-[oxycarbonyl]ethyl)azulene 89, can be used for the protection of carboxylic acids, amines and alcohols as esters, carbamates and carbonates, respectively. The substitution at the 6-position of azulene allows for deprotection through an E1cB mechanism with mild base, involving a cyclopentadienide-stabilised carbanion intermediate, in a similar fashion to the FMOC protecting group. Mild conditions for the protection of all three were found: for carboxylic acids Steglich esterification is employed, and for alcohols and amines coupling with CDI is used. A selection of mild protocols for deprotection were developed, using bases such as DBU or TBAF, or involving two-step activation-deprotection procedures.  Finally, the compatibility of the protecting group 89 (dubbed Azul) with common and representative procedures in synthetic chemistry was investigated, such as with bases and with reaction conditions such as oxidations, reductions, cross-couplings, etc. Orthogonality with other common protecting groups (such as TBS, MOM, FMOC) was also explored. Some incompatibilities were found with strongly acidic conditions, high-temperature Suzuki cross-coupling reactions and Swern oxidations, but otherwise the Azul protecting group shows promise as a protecting group that expedites total synthesis through its colourful properties.</p>

scholarly journals Revisiting NO2 as Protecting Group of Arginine in Solid-Phase Peptide Synthesis

2020 ◽  
Vol 21 (12) ◽  
pp. 4464
Author(s):  
Mahama Alhassan ◽  
Ashish Kumar ◽  
John Lopez ◽  
Fernando Albericio ◽  
Beatriz G. de la Torre
Keyword(s):  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Reaction ◽  
Reducing Agent ◽  
Protecting Groups ◽  
Side Chain ◽  
Protecting Group ◽  
Mild Acid

The protection of side-chain arginine in solid-phase peptide synthesis requires attention since current protecting groups have several drawbacks. Herein, the NO2 group, which is scarcely used, has been revisited. This work shows that it prevents the formation of δ-lactam, the most severe side-reaction during the incorporation of Arg. Moreover, it is stable in solution for long periods and can be removed in an easy-to-understand manner. Thus, this protecting group can be removed while the protected peptide is still anchored to the resin, with SnCl2 as reducing agent in mild acid conditions using 2-MeTHF as solvent at 55 °C. Furthermore, we demonstrate that sonochemistry can facilitate the removal of NO2 from multiple Arg-containing peptides.

Synthetic Versatility of Lipases: Application for Si–O Bond Formation and Cleavage

Synthesis ◽  
2018 ◽  
Vol 51 (02) ◽  
pp. 477-485 ◽  
Author(s):  
Patrícia Brondani ◽  
Mateus Mittersteiner ◽  
Morgana Voigt ◽  
Bruna Klinkowski ◽  
Dilamara Riva Scharf ◽  
...  
Keyword(s):  
Room Temperature ◽  
Bond Formation ◽  
Inert Atmosphere ◽  
Protecting Groups ◽  
Silyl Ether ◽  
Secondary Alcohols ◽  
Protecting Group ◽  
Silyl Ethers ◽  
Dry Conditions ◽  
Silicon Based

Several commercially available lipases were examined in a study on O–Si bond formation and cleavage applying silicon-based protecting groups and alcohols or the corresponding silyl ethers. With regard to deprotection, from silyl ether to the corresponding alcohol, only the solvent and the lipase were necessary. The influence of the protecting group, the lipase source, and the substituent was investigated to optimize the results. The TMS moiety could be removed in 24 hours of reaction at room temperature in aqueous systems (conv. up to 99%, depending on the substrate and lipase). The reverse reactions, that is, with the protection of the alcohols, were carried out in hexane using different silyl chlorides. The TMS, TES, and TBS moieties were successfully inserted in the primary and secondary alcohols without the need for dry conditions or an inert atmosphere, presenting conversions of up to 99%, depending on the substrate.

Thietanyl Protection in the Synthesis of 8-Substituted 1-Benzyl-3-methyl-3,7-dihydro- 1H-purine-2,6-diones

2020 ◽  
Vol 17 (7) ◽  
pp. 535-539
Author(s):  
Ferkat Khaliullin ◽  
Yuliya Shabalina
Keyword(s):  
Hydrogen Peroxide ◽  
Benzyl Chloride ◽  
Bromine Atom ◽  
Protecting Groups ◽  
15N Nmr ◽  
Protecting Group ◽  
Mild Conditions ◽  
Protective Groups ◽  
The Stability ◽  
Substituted 1

Aim and Objective: 1-Аlkyl-3,7-dihydro-1H-purine-2,6-diones containing no substituents in the N7 position can be synthesized only using protecting groups, for example, benzyl protection. However, in the case of synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones, the use of benzyl protection may lead to simultaneous debenzylation of both N1 and N7 positions. Therefore, it is necessary to use other protective groups for the synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones. Materials and Methods: 8-Bromo- and 8-amino-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized with the use of thietanyl protecting group. The thietane ring was introduced via the reaction of 8-bromo-3-methyl-3,7-dihydro-1H-purine-2,6-dione with 2-chloromethylthiirane, giving rise to 8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione. The subsequent alkylation with benzyl chloride yielded 1-benzyl-8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione, which was oxidized with hydrogen peroxide to be converted to 1-benzyl-8-bromo-3-methyl-7-(1,1-dioxothietan- 3-yl)-3,7-dihydro-1H-purine-2,6-dione. This product reacted with amines to give 8-amino-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones. The reaction of 8-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones with sodium isopropoxide resulted in the removal of the thietanyl protection and afforded target 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6- diones. The structures of the targets compounds have been deduced upon their elemental analysis and spectral data (IR, 1H NMR, 13C NMR and 15N NMR). Results and Discussion: A new 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized using thietanyl protecting group. Conclusion: The present study described a new route to synthesize some new 1,8-disubstituted 3-methyl-3,7- dihydro-1H-purine-2,6-diones unsubstituted in the N7 position starting from available 8-bromo-3-methyl-3,7- dihydro-1H-purine-2,6-dione with use of thietanyl protecting group. The advantages of this protocol are the possibility of the synthesis of 1-benzyl-substituted 3,7-dihydro-1H-purine-2,6-diones, the stability of the thietanyl protecting group upon nucleophilic substitution by amines of the bromine atom in the position 8, as well as mild conditions, and simple execution of experiments.

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