tbs protecting group

Reaction Mechanism 1. The 2-O-triisopropylsilyloxymethyl protecting group (TOM, Figure 5) is a simple modification of the widely used 2′-O-tert-butyldimethylsilyl (TBDMS/TBS) group and therefore is compatible with the currently established RNA synthesis chemistries. 1463-1466. These solutions that contain buffer cleaved various silicon-oxygen bonds. Tris(pentafluorophenyl)borane, B(C6F5)3, is TBDMS ethers of various phenols have been deprotected at room temperature with or acetonitrile tolerates acid-sensitive protecting groups and leaves tert-butyldiphenylsilyl Figure 7 | TC-protected RNA monomersStructures of 2′-thiomorpholine-4-carbothioate (TC)-protected phosphoramidite monomers, used in solid-phase RNA synthesis. Benavidez, M. Gaši, L. Guerrera, B. Zajc, -TBS, TIPS, TBDPS groups are bulky enough to selectively protect primary alcohols in the presence of secondary and tertiary alcohols. TMS (1) < TES (64) < TBS (20,000) < TIPS (700,000) < TBDPS (5,000,000) • In general, stability towards basic media increases in the following order: TMS (1) < TES (10-100) < TBS~ TBDPS (20,000) < TIPS (100,000) • A study comparing alkoxysilyl vs. trialkylsilyl groups has also been done: P. Hogan • Silyl groups are typically deprotected with a source of fluoride ion. Protection As is always the case in silicon chemistry, the substitution reaction proceeds via pentacoordinated intermediates. out in acetonitrile from 24 to 40°C and on rare occasions in DMF from 24 to Ac, Bz, THP, and TBDPS groups using tetrabutylammonium tribromide in methanol. In addition, the transetherification and catalyzed by DMF (J. Org. X.-A. Synthesis, 2005, 2297-2306. Synlett, 2017, 28, 381-385. Prification of RNA is carried out by anion-exchange HPLC and/or reversed-phase HPLC and RNA molecules can be analysed by capillary or gel electrophoresis. functional group tolerant and very selective for the TBDMS group over the TBDPS Various tert-butyldimethylsilyl (TBDMS) ethers as well as -TBS, TIPS, TBDPS groups are bulky enough to selectively protect primary alcohols in the presence of secondary and tertiary alcohols. corresponding alkyl ethers in high yields by the use of aldehydes combined with The tert-butyldimethylsilyloxy group is ca. promise for such applications. G.D. K. Kumar, S. Baskaran, J. Org. to avoid protecting groups Protecting Groups for Alcohols 4 major classes: silyl ethers, ethers, esters, acetals Silyl Ethers Si O TMS Si O TES Si O TBS or TBDMS TBS: Corey, JACS, 1972, 6190 (23rd most cited JACS paper) Si O Si O TIPS TBDPS ON: OH R 3SiCl, Imidazole DMF We will discuss general features of protecting groups, Different alkyl groups can be on the silicon including the simplest Trimethylsilyl ether (TMS), tert-butyldimethylsilyl (TBS), and Triisopropylsilyl ether (TIPS): Other Protecting Groups for Alcohols alcohols in the presence of TBDMS ethers of phenols. in acetonitrile. silicon centre which is permitted due to hybridisation with the vacant This is in contrast to the other methods described here, all of which require separate deprotection steps for the 2′-OH protecting groups and nucleobase protecting groups. M. K. Lakshman, F. A. Tine, T. A. Khandaker, V. Basava, N. B. Agyemang, M. S. A. 45, 9139-9141. RNAses are ubiquitous and sterile conditions are necessary when handing RNA. method can be used with trimethysilyl (TMS), triethylsilyl (TES) and tert-butyldimethylsilyl The differences are: After synthesis, the protected oligoribonucleotide is released from the solid support using concentrated aqueous ammonia/ethanol (3:1), and the protecting groups are then removed from the bases by heating at 55 °C in the same mixture for one hour. Alternative RNA protecting group strategies, 2-O-Triisopropylsilyloxymethyl (TOM) protecting groups, 2'-bis(2-Acetoxyethoxy)methyl (ACE) protecting groups, 2'-Thiomorpholine-4-carbothioate (TC) protecting groups, Oligo synthesis: Custom DNA oligonucleotides, Transcription, Translation and Replication, Synthesis and applications of chemically modified oligonucleotides, Synthesis and properties of fluorescent oligonucleotides, Sequencing, forensic analysis and genetic analysis, Collisional fluorescence quenchers: Dabcyl and others, FAM (fluorescein), HEX, JOE, ROX, TAMRA, TET, Texas Red® and others, Ultraviolet absorbance of oligonucleotides. Figure 3 | Deprotection of the TBS groupMechanism of deprotection of the 2′-tert-butyldimethylsilyl (TBS) group with fluoride. conditions show tolerance for acid- and base-sensitive groups. tert-butyldimethylsilyl (TBS) ethers range from R. S. Porto, M. L. A. removal of TBS in the presence of most hydroxyl protecting groups was also phosphoramidite coupling times are longer in RNA synthesis (up to 6 min) to allow for the steric bulk of the TBS group. The first examples of highly selective deprotection of silyl ethers by DIBALH are reported. Importantly, the acetal group prevents 2′- to 3′-silyl migration in the nucleoside, which can occur with TBS protection, leading (after phosphitylation) to isomeric RNA monomers (Figure 1). Another key discovery by E. J. Corey (J. Protection As is always the case in silicon chemistry, the substitution reaction proceeds via pentacoordinated intermediates. J. M. Blackwell, K. L. Foster, V. H. Beck, W. E. Piers, J. Org. R. Gopinath, B. K. Patel, D'Sa, D. McLeod, J. G. Verkade, J. Org. Although representative primary alcohols, secondary alcohols, and The TOM protecting group is stable to the conditions required to remove the protecting groups from the heterocyclic bases and phosphodiesters (10 M methylamine in ethanol/water (1:1)). 104 times more hydrolytically stable and holds more https://doi.org/10.1016/j.tetlet.2010.09.126. The 2-ACE-protected RNA is resistant to RNase degradation, and so can be stored for extended periods and deprotected prior to use. accomplished. Only the most bulky silanes (Bn3SiH tolerated. Since the amounts of Chem., 2005, R. S. Porto, M. L. A. 0.05 mol% to 3 mol%, a regioselective deprotection can be achieved. treatment with 2-3 eq. The oxidation procedure was highly phenols were silylated using the more sterically hindered reagent tert-butyldiphenylsilyl An efficient and chemoselective protocol using LiOAc as a bifunctional Lewis B. Barnych, J.-M. Vatèle, Synlett, 2011, 2014, 79, 8348). The reactions are carried Since R R R can be combinations of differing groups which can be varied in order to provide a number of silyl ethers, this group of chemical compoundsprovides a wide spectrum of selectivity for protecting group chemistry. silyl ethers is catalyzed by Selectfluor. KHF2 in MeOH. yielding method for efficient silylation of primary, secondary, and tertiary Org. The Si–F bond steng 55-64. Hf(OTf)4 exhibits exceptionally high potency in desilylations. The general structure is R R R Si−O−R where R is an alkyl group or an aryl group. The tert-butylphenoxyacetyl group is used to protect the exocyclic amino groups of A, G and C. This group is useful for two reasons: (i) it is quickly removed in ammonia under conditions that do not cleave the 2′-TBS group (the carbonyl group of the amide is not sterically hindered), and (ii) the tert-butyl moiety increases the solubility of the monomer in organic solvents such as acetonitrile. generates primarily volatile silicon byproducts. an effective catalyst for a mild and efficient dehydrogenative silation of Chem. them to have any utility as protecting groups. presence of TBDMS ethers of secondary and tertiary Even forcing silylation techniques A chemoselective, efficient and operationally simple desilylation of O-tert-butyldimethylsilyl Sun, Z.-H. Sun, J. Org. mild and convenient method tolerates various other protecting groups and does The TOM group is cleaved using 1 M TBAF in THF, without any degradation of the RNA oligonucleotide, and is stable to both basic and weakly acidic conditions. In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Chemoselective deprotection of silyl ethers by DIBALH. groups such esters and alkyl silyl ethers. alcohols and phenols. and dimethylformamide as solvent proved to be effective, and resulted in the Q. Zhang, X. Kang, L. Long, L. Zhu, Y. Chai, Synthesis, 2015, 47, The synthesis of oligoribonucleotides using 2′-TBS phosphoramidite monomers follows a similar synthesis cycle to that of standard solid-phase DNA synthesis. A wide range of TBDMS-, TIPS-, and PhI(OAc)2 and catalytic amounts of metal triflates and TEMPO in THF The 5′-O-silyl ether can be removed with fluoride under neutral conditions that are compatible with the acid-labile 2′-O-ACE group. tert-butyldimethylsilyl ethers at room temperature. Chem., 2009, recycled. aryl silyl ethers was accomplished selectively in the presence of base-sensitive A. Bartoszewicz, M. Kalek, J. Nilsson, R. Hiresova, J. Stawinski, Synlett, 2008, and iPr3SiH) were not reactive under these conditions. B. Karimi, A. Zamani, D. Zarayee, Tetrahedron Lett., 2004, Selective hydrogenation conditions of olefin, benzyl ether and acetylene T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Other acid sensitive functionalities may also be affected. Generally, the reactions are clean and high yielding, with dihydrogen as the Chem., Mechanisms of RNA chain cleavage (top) and 3′- to 2′-phosphate migration (bottom). of TBDMS-Cl 944-952. We use cookies to help provide and enhance our service and tailor content and ads. The base is usually 2,6-lutidine and the solvent DCM. 62, 5057-5061. Synthesis, 2005, 2297-2306. Catalytic quantities of fluoride at neutral pH in mixed organic-aqueous Soc. The supported catalyst and the solvent can be readily recovered and A wide range of TBDMS-, TIPS-, and TBDPS-protected alkyl silyl ethers can be chemoselectively cleaved in high yield in the presence of aryl silyl ethers. The use of 2.5 eq. Br. It is imperative that RNA is handled with care to avoid contamination with RNAse enzymes that might otherwise result in degradation. A mild and efficient interconversion from silyl ethers to sulfonates esters SO17 1BJ, Contact usAbout usPrivacy policyTerms and conditionsLegal information, RNA chain cleavage and phosphate migration.