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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Mini-Review Article

Incorporation of Protecting Groups in Organic Chemistry: A Mini-Review

Author(s): Mehmet Murat Kisla*, Mohammed Al-Kassim Hassan, Hind M. Osman, Amine Sena Aydin, Hasan Tahsin Sen, Shan Khazei, Pınar Kul and Canan Kuş

Volume 20, Issue 5, 2023

Published on: 26 December, 2022

Page: [491 - 503] Pages: 13

DOI: 10.2174/1570179419666220820152723

Price: $65

Abstract

The approach of utilizing protecting groups (PGs) in organic chemistry has led to the successful syntheses of an array of useful organic compounds. This strategy has also addressed some of the complexities associated with many organic reactions. These PGs find useful applications in simple and complex reactions that involve the synthesis of large organic compounds such as peptides, and oligosaccharides. The fundamental role of PGs is to prevent undesired reactions that could hinder the progress or completion of such reactions. Ideal PGs must be utilized in this regard to achieve the desired objectives. This review describes the diverse protecting groups found in the literatures, the functional moieties for the protection, deprotection strategies, and their relevant applications in organic synthesis.

Keywords: Protecting groups, deprotection, functional group, organic synthesis, side reactions, oligosaccharides.

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Graphical Abstract

[1]
Patek, M. Multistep deprotection for peptide chemistry. Int. J. Pept. Protein Res., 1993, 42(2), 97-117.
[http://dx.doi.org/10.1111/j.1399-3011.1993.tb00486.x] [PMID: 8407114]
[2]
Barany, G.; Merrifield, R.B. A new amino protecting group removable by reduction. Chemistry of the dithiasuccinoyl (Dts) function. J. Am. Chem. Soc., 1977, 99(22), 7363-7365.
[http://dx.doi.org/10.1021/ja00464a050] [PMID: 915158]
[3]
Wong, C.H.; Ye, X.S.; Zhang, Z. Assembly of oligosaccharide libraries with a designed building block and an efficient orthogonal protection-deprotection strategy. J. Am. Chem. Soc., 1998, 120(28), 7137-7138.
[http://dx.doi.org/10.1021/ja9813616]
[4]
Crimmins, M.T.; Carroll, C.A.; Wells, A.J. Pinacol-type rearrangements of intramolecular photocycloadducts: Application of the 2,2-dimethyl-4-pentenoate protecting group. Tetrahedron Lett., 1998, 39(39), 7005-7008.
[http://dx.doi.org/10.1016/S0040-4039(98)01465-8]
[5]
Masters, J.J.; Link, J.T.; Snyder, L.B.; Young, W.B.; Danishefsky, S.J. Eine totalsynthese von taxol. Angew. Chem., 1995, 107(16), 1886-1888.
[http://dx.doi.org/10.1002/ange.19951071617]
[6]
Masters, J.J.; Link, J.T.; Snyder, L.B.; Young, W.B.; Danishefsky, S.J. A total synthesis of taxol. Angew. Chem. Int. Ed. Engl., 1995, 34(16), 1723-1726.
[http://dx.doi.org/10.1002/anie.199517231]
[7]
Windmüller, R.; Schmidt, R.R. Efficient synthesis of lactoneo series antigens H, Lewis X (Lex), and Lewis Y (Ley)1. Tetrahedron Lett., 1994, 35(43), 7927-7930.
[http://dx.doi.org/10.1016/0040-4039(94)80013-8]
[8]
Nakatsuka, M.; Ragan, J.A.; Sammakia, T.; Smith, D.B.; Uehling, D.E.; Schreiber, S.L. Total synthesis of FK506 and an FKBP probe reagent, [C(8),C(9)-13C2]-FK506. J. Am. Chem. Soc., 1990, 112(14), 5583-5601.
[http://dx.doi.org/10.1021/ja00170a024]
[9]
Piscopio, A.D.; Minowa, N.; Chakraborty, T.K.; Koide, K.; Bertinato, P.; Nicolaou, K.C. A highly convergent strategy towards rapamycin. Stereoselective construction of the C 8 –C 18 fragment. J. Chem. Soc. Chem. Commun., 1993, 7(7), 617-618.
[http://dx.doi.org/10.1039/C39930000617]
[10]
Nicolaou, K.C.; Chakraborty, T.K.; Piscopio, A.D.; Minowa, N.; Bertinato, P. Total synthesis of rapamycin. J. Am. Chem. Soc., 1993, 115(10), 4419-4420.
[http://dx.doi.org/10.1021/ja00063a093]
[11]
Schelhaas, M.; Waldmann, H. Protecting group strategies in organic synthesis. Angew. Chem. Int. Ed. Engl., 1996, 35(18), 2056-2083.
[http://dx.doi.org/10.1002/anie.199620561]
[12]
Kunz, H.; Waldmann, H. Construction of disaccharide N-glycopeptides—synthesis of the linkage region of the transmembrane-neuraminidase of an influenza virus. Angew. Chem. Int. Ed. Engl., 1985, 24(10), 883-885.
[http://dx.doi.org/10.1002/anie.198508831]
[13]
Hayward, C.M.; Yohannes, D.; Danishefsky, S.J. Total synthesis of rapamycin via a novel titanium-mediated aldol macrocyclization reaction. J. Am. Chem. Soc., 1993, 115(20), 9345-9346.
[http://dx.doi.org/10.1021/ja00073a083]
[14]
Hayakawa, Y.; Wakabayashi, S.; Kato, H.; Noyori, R. The allylic protection method in solid-phase oligonucleotide synthesis. An efficient preparation of solid-anchored DNA oligomers. J. Am. Chem. Soc., 1990, 112(5), 1691-1696.
[http://dx.doi.org/10.1021/ja00161a006]
[15]
Blechert, S.; Kleine-Klausing, A. Synthesis of a biologically active taxol analogue. Angew. Chem. Int. Ed. Engl., 1991, 30(4), 412-414.
[http://dx.doi.org/10.1002/anie.199104121]
[16]
Evans, D.A.; Ellman, J.A.; DeVries, K.M. The oxidative macrocyclization of phenolic peptides. A biomimetic approach to the synthesis of the vancomycin family of antibiotics. J. Am. Chem. Soc., 1989, 111(24), 8912-8914.
[http://dx.doi.org/10.1021/ja00206a021]
[17]
Armstrong, R.W.; Beau, J.M.; Cheon, S.H.; Christ, W.J.; Fujioka, H.; Ham, W.H.; Hawkins, L.D.; Jin, H.; Kang, S.H.; Kishi, Y.; Martinelli, M.J.; McWhorter, W.W.; Mizuno, M.; Nakata, M.; Stutz, A.E.; Talamas, F.X.; Taniguchi, M.; Tino, J.A.; Ueda, K.; Uenishi, J. Total synthesis of a fully protected palytoxin carboxylic acid. J. Am. Chem. Soc., 1989, 111(19), 7525-7530.
[http://dx.doi.org/10.1021/ja00201a037]
[18]
Wuts, P.G.; Greene, T.W. Greene’s Protective Groups in Organic Synthesis, 3rd ed; John Wiley & Sons: New York, 1999.
[19]
Kocienski, P.J. Protecting Groups, 3rd ed; Thieme: Stuttgart, 2005.
[http://dx.doi.org/10.1055/b-003-108603]
[20]
Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 4th ed; John Wiley & Sons: New Jersey, 2007.
[21]
Corey, E.J.; Venkateswarlu, A. Protection of hydroxyl groups as tert-butyldimethylsilyl derivatives. J. Am. Chem. Soc., 1972, 94(17), 6190-6191.
[http://dx.doi.org/10.1021/ja00772a043]
[22]
Protecting groups for alcohols. Available from: https://www.chemistrysteps.com/protecting-groups-for-alcohols/ (Accessed on: 6 April, 2021).
[23]
Ghosh, B.; Kulkarni, S.S. Advances in protecting groups for oligosaccharide synthesis. Chem. Asian J., 2020, 15(4), 450-462.
[http://dx.doi.org/10.1002/asia.201901621] [PMID: 31895493]
[24]
Holton, R.A.; Somoza, C.; Kim, H.B.; Liang, F.; Biediger, R.J.; Boatman, P.D.; Shindo, M.; Smith, C.C.; Kim, S. First total synthesis of taxol. 1. Functionalization of the B ring. J. Am. Chem. Soc., 1994, 116(4), 1597-1598.
[http://dx.doi.org/10.1021/ja00083a066]
[25]
Geiger, R.; König, W. Amine protecting groups.In: Protection of functional groups in peptide synthesis: The peptides: Analysis, synthesis and biology; Gross, E.; Meienhofer, J., Eds.; Academic Press, 1981, Vol. 3, pp. 1-99.
[26]
Ashenhurst, J. Introduction to peptide synthesis., Available from: https://www.masterorganicchemistry.com/2019/02/15/introduction-to-peptide-synthesis/ (Accessed on 6 April, 2021).
[27]
Roberts, J.D.; Caserio, M.C. Protection of amino groups in synthesis., Available from: https://chem.libretexts.org/@go/page/22348 (Accessed on: 6 April, 2021).
[28]
Roberts, J.D.; Caserio, M.C. Basic Principles of Organic Chemistry, 2nd ed; W.A. Benjamin, Inc.: Menlo Park, CA, 1977.
[29]
Mutter, M.; Hersperger, R. Efficient synthesis of N-triphenylmethyl α-amino acids. Synthesis, 1989, 1989(3), 198-200.
[http://dx.doi.org/10.1055/s-1989-27195]
[30]
Garro-Helion, F.; Merzouk, A.; Guibe, F. Mild and selective palladium(0)-catalyzed deallylation of allylic amines. Allylamine and diallylamine as very convenient ammonia equivalents for the synthesis of primary amines. J. Org. Chem., 1993, 58(22), 6109-6113.
[http://dx.doi.org/10.1021/jo00074a044]
[31]
Poole, L.B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med., 2015, 80, 148-157.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.11.013] [PMID: 25433365]
[32]
Winterbourn, C.C.; Hampton, M.B. Thiol chemistry and specificity in redox signaling. Free Radic. Biol. Med., 2008, 45(5), 549-561.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.05.004] [PMID: 18544350]
[33]
Couvertier, S.M.; Zhou, Y.; Weerapana, E. Chemical-proteomic strategies to investigate cysteine posttranslational modifications. Biochim. Biophys. Acta. Proteins Proteomics, 2014, 1844(12), 2315-2330.
[http://dx.doi.org/10.1016/j.bbapap.2014.09.024] [PMID: 25291386]
[34]
Haugaard, N. Reflections on the role of the thiol group in biology. Ann. N. Y. Acad. Sci., 2000, 899(1), 148-158.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06183.x] [PMID: 10863536]
[35]
Akabori, S.; Sakakibara, S.; Shimonishi, Y.; Nobuhara, Y. A new method for the protection of the sulfhydryl group during peptide synthesis. Bull. Chem. Soc. Jpn., 1964, 37(3), 433-434.
[http://dx.doi.org/10.1246/bcsj.37.433]
[36]
Hiskey, R.G. Sulfhydryl group protection in peptide synthesis.In: Protection of Functional Groups in Peptide Synthesis: The Peptides: Analysis, Synthesis and Biology; Gross, E.; Meienhofer, J., Eds.; Academic Press, 1981, Vol. 3, pp. 137-167.
[37]
Isidro-Llobert, A.; Alvarez, M.; Albericio, F. Amino acid-protecting groups. Chem. Rev., 2009, 109(6), 2455-2504.
[38]
Richter, L.S.; Marsters, J.C., Jr; Gadek, T.R. Two new procedures for the introduction of benzyl-type protecting groups for thiols. Tetrahedron Lett., 1994, 35(11), 1631-1634.
[http://dx.doi.org/10.1016/0040-4039(94)88305-X]
[39]
Westheimer, F.H. Why nature chose phosphates. Science, 1987, 235(4793), 1173-1178.
[http://dx.doi.org/10.1126/science.2434996] [PMID: 2434996]
[40]
Cox, J.R., Jr; Ramsay, O.B. Mechanisms of nucleophilic substitution in phosphate esters. Chem. Rev., 1964, 64(4), 317-352.
[http://dx.doi.org/10.1021/cr60230a001]
[41]
Burger, A.; Anderson, J.J. Monoesters and ester-amidates of aromatic phosphonic acids. J. Am. Chem. Soc., 1957, 79(13), 3575-3579.
[http://dx.doi.org/10.1021/ja01570a073]
[42]
Zwierzak, A.; Kluba, M. Organophosphorus esters-I. Tetrahedron, 1971, 27(14), 3163-3170.
[http://dx.doi.org/10.1016/S0040-4020(01)98109-8]
[43]
Jackson, W.R.; Moffat, M.R.; Perlmutter, P.; Tasdelen, E.E. The stereochemistry of organometallic compounds. XXXVIII. Regio-and stereo-control in the rhodium-catalyzed hydroformylation of some alkenyl phosphites. Aust. J. Chem., 1992, 45(5), 823-834.
[http://dx.doi.org/10.1071/CH9920823]
[44]
Moriguchi, T.; Wada, T.; Sekine, M. New nucleoside-sugar conjugates: 6-N-glycosyloxyphosphorylated adenosine derivatives as partial structures of agrocin 84. J. Org. Chem., 1996, 61(26), 9223-9228.
[http://dx.doi.org/10.1021/jo961489a]
[45]
Van Boom, J.H.; Burgers, P.M.J.; Verdegaal, C.H.M.; Wille, G. Synthesis of oligonucleotides with sequences identical with or analogous to the 3′-end of 16s ribosomal rna of escherichia coli: Preparation op U-C-C-U-U-A and A-C-C-U-C-C-U-U-A via the modified phosphotriester method. Tetrahedron, 1978, 34(13), 1999-2007.
[http://dx.doi.org/10.1016/0040-4020(78)80109-4]
[46]
Sim, M.M.; Kondo, H.; Wong, C.H. Synthesis and use of glycosyl phosphites: An effective route to glycosyl phosphates, sugar nucleotides, and glycosides. J. Am. Chem. Soc., 1993, 115(6), 2260-2267.
[http://dx.doi.org/10.1021/ja00059a023]
[47]
Dahl, B.H.; Bjergårde, K.; Henriksen, L.; Dahl, O.; Nielsen, M.; Lehmann, M.S.; Tokii, T. A highly reactive, odourless substitute for thiophenol/triethylamine as a deprotection reagent in the synthesis of oligonucleotides and their analogues. Acta Chem. Scand., 1990, 44, 639-641.
[http://dx.doi.org/10.3891/acta.chem.scand.44-0639]
[48]
Perich, J.W.; Alewood, P.F.; Johns, R.B. Synthesis of casein-related peptides and phosphopeptides. VII. The efficient synthesis of ser (p)-containing peptides by the use of Boc-Ser (PO3R2)-OH derivatives. Aust. J. Chem., 1991, 44(2), 233-252.
[http://dx.doi.org/10.1071/CH9910233]
[49]
Givens, R.S.; Kueper, L.W. Photochemistry of phosphate esters. Chem. Rev., 1993, 93(1), 55-66.
[http://dx.doi.org/10.1021/cr00017a004]
[50]
Ohtsuka, E.; Morioka, S.; Ikehara, M.; Polynucleotides, X.I.X. Synthesis of oligonucleotides by the use of the N-trityl-p-aminophenyl group, a new protecting group for the terminal phosphate residues. J. Am. Chem. Soc., 1973, 95(25), 8437-8440.
[http://dx.doi.org/10.1021/ja00806a039] [PMID: 4773248]
[51]
Jones, S.S.; Reese, C.B. Chemical synthesis of 5′-O-triphosphoryladenylyl-(2′. fwdarw. 5′)-adenylyl-(2′. fwdarw. 5′)-adenosine (2-5A). J. Am. Chem. Soc., 1979, 101(24), 7399-7401.
[http://dx.doi.org/10.1021/ja00518a046]
[52]
Engels, J. Selective electrochemical removal of protecting groups in nucleotide synthesis. Angew. Chem. Int. Ed. Engl., 1979, 18(2), 148-149.
[http://dx.doi.org/10.1002/anie.197901481]
[53]
Roy, B.; Depaix, A.; Périgaud, C.; Peyrottes, S. Recent trends in nucleotide synthesis. Chem. Rev., 2016, 116(14), 7854-7897.
[http://dx.doi.org/10.1021/acs.chemrev.6b00174] [PMID: 27319940]
[54]
Liu, L.; Pohl, N.L.B. A fluorous phosphate protecting group with applications to carbohydrate synthesis. Org. Lett., 2011, 13(7), 1824-1827.
[http://dx.doi.org/10.1021/ol2003435] [PMID: 21384825]
[55]
Greene, T.W. Protective groups in organic synthesis; John Wiley & Sons: New York, 1981, p. 108.
[56]
Kabalka, G.W.; Varma, M.; Varma, R.S.; Srivastava, P.C.; Knapp, F.F., Jr The tosylation of alcohols. J. Org. Chem., 1986, 51(12), 2386-2388.
[http://dx.doi.org/10.1021/jo00362a044]
[57]
Sridhar, M.; Kumar, B.A.; Narender, R. Expedient and simple method for regeneration of alcohols from toluenesulfonates using Mg-MeOH. Tetrahedron Lett., 1998, 39(18), 2847-2850.
[http://dx.doi.org/10.1016/S0040-4039(98)00314-1]
[58]
Corey, E.J.; Rücker, C. Useful synthetic reagents derived from 1-triisopropylsilylpropyne and 1,3-[triisopropylsilyl]propyne, direct, stereoselective synthesis of either or enynes. Tetrahedron Lett., 1982, 23(7), 719-722.
[http://dx.doi.org/10.1016/S0040-4039(00)86930-0]
[59]
Kownacki, I.; Marciniec, B.; Dudziec, B.; Kubicki, M. Silylative coupling of terminal alkynes with iodosilanes: New catalytic activation of sp-hybridized carbon-hydrogen bonds. Organometallics, 2011, 30(9), 2539-2545.
[http://dx.doi.org/10.1021/om200038r]
[60]
Toutov, A.A.; Betz, K.N.; Schuman, D.P.; Liu, W.B.; Fedorov, A.; Stoltz, B.M.; Grubbs, R.H. Alkali metal-hydroxide-catalyzed C (sp)-H bond silylation. J. Am. Chem. Soc., 2017, 139(4), 1668-1674.
[http://dx.doi.org/10.1021/jacs.6b12114] [PMID: 28026952]
[61]
López, S.; Fernández-Trillo, F.; Castedo, L.; Saá, C. Synthesis of callyberynes A and B, polyacetylenic hydrocarbons from marine sponges. Org. Lett., 2003, 5(20), 3725-3728.
[http://dx.doi.org/10.1021/ol0354270] [PMID: 14507215]
[62]
Chinchilla, R.; Nájera, C. Recent advances in Sonogashira reactions. Chem. Soc. Rev., 2011, 40(10), 5084-5121.
[http://dx.doi.org/10.1039/c1cs15071e] [PMID: 21655588]
[63]
Nielsen, M. Sonogashira-like coupling reactions with phosphine–gold (I) alkynyl complexes. Synthesis, 2016, 48(17), 2732-2738.
[http://dx.doi.org/10.1055/s-0035-1561664]
[64]
Larson, G. Some aspects of the chemistry of alkynylsilanes. Synthesis, 2018, 50(13), 2433-2462.
[http://dx.doi.org/10.1055/s-0036-1591979]
[65]
Gross, E.; Meienhofer, J. Protection of Functional Groups in Peptide Synthesis: The Peptides Analysis, Synthesis, Biology; Elsevier, 2014, 3.
[66]
Hansen, P.R.; Oddo, A. Fmoc Solid-phase peptide synthesis.In: Peptide Antibodies: Methods in Molecular Biology; Houen, G., Ed.; Humana Press: New York, 2015, Vol. 1348, pp. 33-50.
[http://dx.doi.org/10.1007/978-1-4939-2999-3_5]
[67]
Tymecka, D.; Misicka, A. Solution phase peptide synthesis: The case of biphalin.In: Peptide Synthesis: Methods and Protocols. Methods in Molecular Biology; Humana Press: New York, 2020, Vol. 2103, pp. 1-11.
[http://dx.doi.org/10.1007/978-1-0716-0227-0_1]
[68]
Conda-Sheridan, M.; Krishnaiah, M. Protecting groups in peptide synthesis.In: Peptide Synthesis. Methods and Protocols; Hussein, W.M.; Skwarczynski, M.; Toth, I., Eds.; Humana Press: New York, 2020, pp. 111-128.
[http://dx.doi.org/10.1007/978-1-0716-0227-0_7]
[69]
Orain, D.; Ellard, J.; Bradley, M. Protecting groups in solid-phase organic synthesis. J. Comb. Chem., 2002, 4(1), 1-16.
[http://dx.doi.org/10.1021/cc0001093] [PMID: 11790135]
[70]
Petrou, C.; Sarigiannis, Y. Peptide synthesis.In: Peptide Applications in Biomedicine, Biotechnology and Bioengineering; Koutsopoulos, S., Ed.; Woodhead Publishing: Elsevier, 2018, pp. 1-21.
[http://dx.doi.org/10.1016/B978-0-08-100736-5.00001-6]
[71]
Mäde, V.; Els-Heindl, S.; Beck-Sickinger, A.G. Automated solid-phase peptide synthesis to obtain therapeutic peptides. Beilstein J. Org. Chem., 2014, 10(1), 1197-1212.
[http://dx.doi.org/10.3762/bjoc.10.118] [PMID: 24991269]
[72]
Thieriet, N.; Guibé, F.; Albericio, F. Solid-phase peptide synthesis in the reverse (N --> C) direction. Org. Lett., 2000, 2(13), 1815-1817.
[http://dx.doi.org/10.1021/ol0058341] [PMID: 10891165]
[73]
Karskela, T. Solid-phase organic synthesis: Bicyclic peptides and purine- derived small molecules, PhD Dissertation, University of Turku: Finland, 2013.
[74]
Wong, C.H.; Zimmerman, S.C. Orthogonality in organic, polymer, and supramolecular chemistry: From Merrifield to click chemistry. Chem. Commun., 2013, 49(17), 1679-1695.
[http://dx.doi.org/10.1039/c2cc37316e] [PMID: 23282586]

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