Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Bimodal Glycosyl Donors Protected by 2-O‑(orthoTosylamido)benzyl Group Feiqing Ding, Akihiro Ishiwata,* and Yukishige Ito* Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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S Supporting Information *
ABSTRACT: A glucosyl donor equipped with C2-o-TsNHbenzyl ether was shown to provide both α- and β-glycosides stereoselectivity, by changing the reaction conditions. Namely, β-glycosides were selectively obtained when the trichloroacetimidate was activated by Tf2NH. On the other hand, activation by TfOH in Et2O provided α-glycosides as major products. This “single donor” approach was employed to assemble naturally occurring trisaccharide α-D-Glc-(1→2)-α-DGlc-(1→6)-D-Glc and its anomers.
S
Scheme 1. Preparation of C2-o-TsNHbenzyl D-Glucosyl Trichloroacetimidate 6b as Donor
tereoselective O-glycosylation is essential in order for the efficient synthesis of biologically relevant oligosaccharides.1 The performance of such reactions is influenced by a variety of factors including the leaving group, the activator, protective groups, and reaction conditions.2 In most cases, 1,2trans glycosylation has exploited neighboring-group participation (NGP) of a 2-O-acyl group.3 On the other hand, donors having 2-O-ether protection favor the formation of axial glycosides for stereoelectronic reasons (Figure 1, donor 1).4 Aimed at achieving stereocontrolled glycosylation, nonclassical NGP strategies involving C2 chiral auxiliaries (Figure
1, 2)5 or the 2-O-picolyl group (3) have been developed.3a,6 More recently, the use of 2-O-ortho-substituted benzyl groups such as o-nitrobenzyl (4)7 and o-cyanobenzyl (5)8 have shown to be effective for the formation of 1,2-trans-glycosides (Figure 1, donor 4 and donor 5). In spite of these, synthetic schemes for complex oligosaccharides are usually complicated, because formation of 1,2-cis and -trans glycosides usually requires distinct donors. A generalized strategy for the stereoselective synthesis of both Figure 1. Application of the ether-type participating groups in glycosylation reactions. © XXXX American Chemical Society
Received: June 20, 2018
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DOI: 10.1021/acs.orglett.8b01922 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Screening of Reaction Conditionsa
Scheme 2. Glycosylation with Various Acceptorsa
entry
cat.
solvent (M)
t (°C)
yield (%)b
α:βc
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
TMSOTf TMSOTf TMSOTf TMSOTf Tf2NH Tf2NH Tf2NH Tf2NH Tf2NH TMSOTf TMSOTf TMSOTf TfOH Cu(OTf)2 AgOTf ZnBr2 TfOH TfOH TfOH TfOH TfOH
toluene (0.1) MeCN (0.1) DCM (0.1) DCM (0.1) EtCN (0.1) DCM (0.1) toluene (0.1) Et2O (0.1) Et2O (0.1) THF (0.1) Et2O (0.1) Et2O (0.1) Et2O (0.1) Et2O (0.1) Et2O (0.1) Et2O (0.1) Et2O (0.01) Et2O (0.004) Et2O (0.004) Et2O (0.004) Et2O (0.004)
0 0 0 −78d −78d −78d −78d −78d rt 0 0 rt rt rt rt rt rt rt 0 −40d −78d
98 95 99 93 91 87 85 84 90 94 92 96 92 88 14 74 95 71e 92 87 72
35:65 13:87 33:67 2:98 β β β 14:86 39:61 55:45 73:27 74:26 76:24 75:25 62:18 77:23 81:19 84:16 74:26 71:29 69:31
a Reaction conditions: donor 6b (1.0 equiv), cyclohexanol 8a (1.2 equiv), catalyst (0.1 equiv), MS 3 Å (100 mg/mL). bCombined yield of the anomeric mixture of corresponding glycoside. cDetermined by the integration ratio obtained from 1H NMR of crude mixture. dFor 2 h. eIsolated yield of corresponding α-glycoside.
isomers from a single donor has yet to be established. With the goal of achieving stereocontrolled construction of both α- and β-glycosidic bonds from a single donor, our attention was turned to the 2-O-(ortho-tosylamido)benzyl (TAB) modified donor 6 (Figure 1).9 We expected that its behavior could be tuned by modulating the internal hydrogen bonding with the C-2 oxygen (A) or the incoming nucleophile (B). As a prototypical donor, we designed the trichloroacetimidate 6b which was prepared, as depicted in Scheme 1. To evaluate the stereodirecting ability of the 2-O-TAB group, initial experiments were carried out using cyclohexanol (8a) as an acceptor. In the presence of 10 mol % of TMSOTf (Table 1, entries 1−5), the product 9a was obtained in modest to high stereoselectivity which favored the β-isomer (α/β = 33/67 to 2/98) (entries 1−4). In the presence of triflimide (Tf2NH),10 nearly complete selectivity was observed in EtCN, DCM, or toluene (entries 5−7). Interestingly, the β-isomer was still dominant in Et2O at low temperature (entry 8, α/β = 14/86). By contrast, variable α-selectivity was observed when other Brønsted or Lewis acids were employed in ether (Table 1, entries 11−21). Screening of the reaction conditions revealed that (1) TfOH was most effective, (2) α-selectivity was enhanced at lower concentration, and (3) lowering the reaction temperature was not beneficial. The scope of the reaction was assessed under conditions A (Table 1, entry 5) and B (Table 1, entry 18), which are suitable for 1,2-cis and -trans selective glucosylations, respectively (Scheme 2). Under conditions A, reactions with benzyl alcohol (8b), 1-adamantanol (8c), and L-menthol (8h) gave corresponding glycosides 9b and 9c with complete βstereoselectivity, whereas tert-butanol (8d) exhibited lower selectivity. In contrast, conditions B predominantly gave αisomers (α/β = 85/15 to 92/8). Subsequently, steroids (8i−j),
a
Conditions A: entry 5, Table 1; conditions B: entry 18, Table 1. Determined by the integration ratio obtained from 1H NMR of crude mixture. b
Scheme 3. Stereocontrolled Galactosylationa
a
Conditions A: entry 5, Table 1; conditions B: entry 18, Table 1. Determined by the integration ratio obtained from 1H NMR of crude mixture. b
protected amino acids (8e−g),11 and glycosides 8k−q12 were examined as acceptors. β-Glucosylated products (9k−q) were obtained in good yield and excellent stereoselectivity under conditions A, whereas 9m and 9n were obtained as mixtures of isomers. In the latter cases, conditions B exhibited excellent αselectivity. Similarly, α-glucosides were obtained from 8k (GlcO‑6), 8l (GlcO‑4), 8o (GlcO‑2), 8p (ManO‑2), and 8q (βGalO‑3-(1→4)-Glc), albeit in somewhat attenuated selectivity. B
DOI: 10.1021/acs.orglett.8b01922 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 4. (A) Structures of Isomeric Trisaccharides D-Glc(1→2)-D-Glc-(1→6)-D-Glc; (B) Selective Deprotection of Bn and TsNHBn Ethers
Scheme 6. Reactions of the 2-O-Benzylated Donor 1b
Scheme 7. Proposed Mechanism for α- and β-Selective Glycosylations
standard debenzylation conditions (Scheme 4). Conversely, removal of benzyl groups was achieved by DDQ without deteriorating the TAB group to give 15 (Scheme 4). Selective cleavage of the TAB ether was achieved in three steps through Boc protection, deprotection of the tosyl group by Mg treatment, and treatment with DDQ to give 17 with complete preservation of the benzyl groups (Scheme 4). Our protocol for the selective cleavage of the TAB ether could be completed in 24 h which was sufficient for the current purpose. Indeed, disaccharides β-9k and α-9k were efficiently converted to β-21 and α-21 via corresponding 18, 19, and 20, in 46% and 53% overall yields, respectively (Scheme 5). Subsequent glycosylation of β-21 with 6b under conditions A produced the trisaccharide β-D-Glc-(1→2)-β-D-Glc-(1→6)-αD-Glc-OMe (22) in a highly stereoselective fashion. Coupling under conditions B produced isomeric trisaccharide α-D-Glc(1→2)-β-D-Glc-(1→6)-α-D-Glc-OMe (23) in 61% yield.
Acid-labile groups such as t-Bu, Boc, and benzylidene acetal were compatible with both conditions. We also examined the effects of the 2-O-TAB group for galactosylation. To this end, the galactose donor 6c was prepared (see Supporting Information) and reacted with 8a, 8j, 8k, and 8n (Scheme 3). Similarly to 6a, it produced the corresponding β- (β-9r−9u) and α-galactosides (α-9r−9u) under conditions A and B, respectively. Subsequently, we planned to assemble all four isomers of trisaccharides D-Glc-(1→2)-D-Glc-(1→6)-D-Glc13 (10−13) (Scheme 4) using 6b as the common donor. To put our plan into practice, selective deprotection of the TsNHBn group was examined first. Initially, the glycosylated product α-9a was subjected to hydrogenolysis (H2, Pd/C) to produce the tetraol 14, confirming that the TAB group is removable under
Scheme 5. Synthesis of Four Isomers of D-Glc-(1→2)-D-Glc-(1→6)-D-Glc Using 6b as a Common Donor
C
DOI: 10.1021/acs.orglett.8b01922 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Similarly, α-21 obtained from α-9k led to the trisaccharides βD-Glc-(1→2)-α-D-Glc-(1→6)-α-D-Glc-OMe (24) (conditions A: α/β = 8/92, 59% isolated yield of the β-isomer) and α-DGlc-(1→2)-α-D-Glc-(1→6)-α-D-Glc-OMe (25) (conditions B: α/β = 90/10, 47% isolated yield of the α-isomer), respectively. All four isomers of D-Glc-(1→2)-D-Glc-(1→6)-α-D-Glc-OMe (10−13) were obtained after conventional mild global deprotections of the protected trisaccharides (Scheme 5). These results indicate that the TAB group behaves differently in ethereal and nonethereal solvents, serving as an NGP active substituent in DCM, toluene, and EtCN. Reactions using perbenzylated donor 1b provided corresponding glycoside 26 with diminished stereoselectivity (α/β = 11/ 89 compared to β-only for 6b), while the stereoselectivity was similar between 1b and 6b (α/β = 83/17 and 84/16) under conditions B (Scheme 6). To explain the stereodirecting effects of the TAB group, we postulate the contribution of a hydrogen bonding between tosylamide and the benzylic oxygen, as NH signals of donor (1d) and glycosides (3) were significantly shifted downfield (∼8 ppm). The proposed quasi-bicyclic form I is reminiscent of a 2-phthalimide group, which is well-known to be powerful as a 1,2-trans directing group.14 Subsequent formation of the oxocarbenium ion would initiate NGP by the sulfonamide oxygen (i.e., formation of II) to give β-glycosides. On the other hand, the intramolecular hydrogen is likely to be disrupted in ether, leading the TAB group into NGP inactive form III. This view was reinforced by control experiments conducted in the absence of alcohol. When the donor was activated under conditions A, β-trichloroacetamide 27 was obtained. On the other hand, conditions B afforded seven-membered cyclic Nglucoside 28 as a mixture of anomers (α/β = 87/13), suggesting that the tosylamide group is relieved of the internal oxygen and able to attack the anomeric position intramolecularly (Scheme 7). In summary, we have developed a glycosyl donor having oTsNHbenzyl ether as a stereodirecting element, which allows for α- or β-stereoselective glycoylation by switching conditions. This approach was applied to the synthesis of all four isomers of the naturally occurring trisaccharides D-Glc-(1→2)-D-Glc(1→6)-D-Glc. Clarification of its mechanistic detail, optimization of reaction conditions, and expansion to other sugar components will be subjects of future study.15
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Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank Dr. Takemichi Nakamura and Dr. Hiroyuki Koshino (RIKEN, CSRS) for measurement of mass spectra and lowtemperature NMR measurements, respectively. We also thank Ms. Akemi Takahashi (RIKEN, SCCL) for technical assistance. This work was partly supported by a Grant-in-Aid for Specially Promoted Research (No. 16H06290 to YI) from the Ministry of Education, Culture, Sports, Science, and Technology, for Scientific Research (No. 26350966, 15H02443 to AI) from the Japan Society for the Promotion of Science, and Special Postdoctoral Program (FD) from RIKEN.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b01922. Experimental and spectral data (PDF)
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REFERENCES
(1) Selected reviews: (a) Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900−1934. (b) Seeberger, P. H. Acc. Chem. Res. 2015, 48, 1450−1463. (c) Danishefsky, S. J.; Shue, Y.-K.; Chang, M. N.; Wong, C.-H. Acc. Chem. Res. 2015, 48, 643−652. (d) Wang, Z.; Chinoy, Z. S.; Ambre, S. G.; Peng, W.; McBride, R.; de Vries, R. P.; Glushka, J.; Paulson, J. C.; Boons, G.-J. Science 2013, 341, 379−383. (e) Yang, Y.; Zhang, X.; Yu, B. Nat. Prod. Rep. 2015, 32, 1331−1355. (f) Ranade, S. C.; Demchenko, A. V. J. Carbohydr. Chem. 2013, 32, 1−43. (g) Guo, J.; Ye, X.-S. Molecules 2010, 15, 7235−7265. (2) Selected recent examples: (a) Boltje, T. J.; Buskas, T.; Boons, G.J. Nat. Chem. 2009, 1, 611−622. (b) Ishiwata, A.; Kaeothip, S.; Takeda, Y.; Ito, Y. Angew. Chem., Int. Ed. 2014, 53, 9812−9816. (c) Park, Y.; Harper, K. C.; Kuhl, N.; Kwan, E. E.; Liu, R. Y.; Jacobsen, E. N. Science 2017, 355, 162−166. (d) Sun, L.; Wu, X.; Xiong, D.-C.; Ye, X.-S. Angew. Chem., Int. Ed. 2016, 55, 8041−8044. (e) Shu, P.; Xiao, X.; Zhao, Y.; Xu, Y.; Yao, W.; Tao, J.; Wang, H.; Yao, G.; Lu, Z.; Zeng, J.; Wan, Q. Angew. Chem., Int. Ed. 2015, 54, 14432−14436. (f) Xiao, X.; Zhao, Y.; Shu, P.; Zhao, X.; Liu, Y.; Sun, J.; Zhang, Q.; Zeng, J.; Wan, Q. J. Am. Chem. Soc. 2016, 138, 13402− 13407. (g) Liu, H.; Zhang, Y.; Wei, R.; Andolina, G.; Li, X. J. Am. Chem. Soc. 2017, 139, 13420−13428. (3) Selected examples: (a) Smoot, J. T.; Pornsuriyasak, P.; Demchenko, A. V. Angew. Chem., Int. Ed. 2005, 44, 7123−7126. (b) Yamada, T.; Takemura, K.; Yoshida, J.; Yamago, S. Angew. Chem., Int. Ed. 2006, 45, 7575−7578. (c) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Danishefsky, S. J. J. Am. Chem. Soc. 1997, 119, 10064−10072. (d) Ye, X.-S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410−2431. (e) Fürstner, A.; Jeanjean, F.; Razon, P.; Wirtz, C.; Mynott, R. Chem. - Eur. J. 2003, 9, 320−326. (f) Ning, J.; Zhang, W.; Yi, Y.; Yang, G.; Wu, Z.; Yi, J.; Kong, F. Bioorg. Med. Chem. 2003, 11, 2193−2203. (g) Pleuss, N.; Kunz, H. Angew. Chem., Int. Ed. 2003, 42, 3174−3176. (h) Orgueira, H. A.; Bartolozzi, A.; Schell, P.; Litjens, R. E. J. N.; Palmacci, E. R.; Seeberger, P. H. Chem. - Eur. J. 2003, 9, 140. (i) Dziadek, S.; Brocke, C.; Kunz, H. Chem. - Eur. J. 2004, 10, 4150− 4162. (j) Rele, S. M.; Iyer, S. S.; Baskaran, S.; Chaikof, E. L. J. Org. Chem. 2004, 69, 9159−9170. (k) Zhu, X.; Yu, B.; Hui, Y.; Schmidt, R. R. Eur. J. Org. Chem. 2004, 965−973. (4) (a) Bols, M.; Hansen, H. C. Chem. Lett. 1994, 23, 1049−1052. (b) Crich, D.; Sharma, I. J. Org. Chem. 2010, 75, 8383−8391. (c) Kim, K. S.; Suk, D.-H. Trends Glycosci. Glycotechnol. 2011, 23, 53− 65. (d) Ishiwata, A.; Ito, Y. J. Am. Chem. Soc. 2011, 133, 2275−2291. (5) (a) Kim, J.-H.; Yang, H.; Park, J.; Boons, G.-J. J. Am. Chem. Soc. 2005, 127, 12090−12097. (b) Boltje, T. J.; Kim, J.-H.; Park, J.; Boons, G.-J. Org. Lett. 2011, 13, 284−287. (c) Stalford, S. A.; Kilner, C. A.; Leach, A. G.; Turnbull, W. B. Org. Biomol. Chem. 2009, 7, 4842− 4852. (d) Fascione, M. A.; Adshead, S. J.; Stalford, S. A.; Kilner, C. A.; Leach, A. G.; Turnbull, W. B. Chem. Commun. 2009, 5841−5843. (e) Cox, D. J.; Fairbanks, A. J. Tetrahedron: Asymmetry 2009, 20, 773−780.
AUTHOR INFORMATION
Corresponding Authors
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[email protected]. ORCID
Feiqing Ding: 0000-0002-0211-7101 Akihiro Ishiwata: 0000-0002-5542-2214 Yukishige Ito: 0000-0001-6251-7249 D
DOI: 10.1021/acs.orglett.8b01922 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters (6) (a) Smoot, J. T.; Demchenko, A. V. J. Org. Chem. 2008, 73, 8838−8850. (b) Yasomanee, J. P.; Demchenko, A. V. J. Am. Chem. Soc. 2012, 134, 20097−20102. (c) Pistorio, S. G.; Yasomanee, J. P.; Demchenko, A. V. Org. Lett. 2014, 16, 716−719. (7) Buda, S.; Gołębiowska, P.; Mlynarski, J. Eur. J. Org. Chem. 2013, 3988−3991. (8) (a) Hoang, K. L. M.; Liu, X.-W. Nat. Commun. 2014, 5, 5051− 5059. (b) Buda, S.; Nawój, M.; Gołębiowska, P.; Dyduch, K.; Michalak, A.; Mlynarski, J. J. Org. Chem. 2015, 80, 770−780. (9) (a) Di Bussolo, V.; Caselli, M.; Romano, M. R.; Pineschi, M.; Crotti, P. J. Org. Chem. 2004, 69, 7383−7386. (b) Di Bussolo, V.; Romano, M. R.; Pineschi, M.; Crotti, P. Org. Lett. 2005, 7, 1299− 1302. (c) Ding, F.; William, R.; Wang, F.; Ma, J.; Ji, L.; Liu, X.-W. Org. Lett. 2011, 13, 652−655. (d) Ding, F.; William, R.; Wang, S.; Gorityala, B. K.; Liu, X.-W. Org. Biomol. Chem. 2011, 9, 3929−3939. (e) Ding, F.; William, R.; Cai, S. T.; Ma, J.; Liu, X.-W. J. Org. Chem. 2012, 77, 5245−5254. (10) (a) Kowalska, K.; Pedersen, C. M. Chem. Commun. 2017, 53, 2040−2043. (b) Ding, F.; William, R.; Wang, F.; Liu, X.-W. Chem. Commun. 2012, 48, 8709−8711. (c) Mundal, D. A.; Avetta, C., Jr.; Thomson, R. J. Nat. Chem. 2010, 2, 294−297. (d) Boxer, M. B.; Yamamoto, Y. Nat. Protoc. 2006, 1, 2434−2438. (11) (a) Mastalic, J.; Jerković, I.; Vinković, V.; Dzolić, Z.; VikićTopić, D. Croat. Chem. Acta 2004, 77, 491−500. (b) Noguchi, K.; Nakagawa, H.; Yoshiyama, M.; Shimura, S.; Kirimura, K.; Usami, S. J. Ferment. Bioeng. 1998, 85, 436−438. (c) Yamauchi, T.; Hara, M.; Mihashi, K. Phytochemistry 1972, 11, 3345−3347. (12) (a) Tejler, J.; Tullberg, E.; Frejd, T.; Leffler, H.; Nilsson, U. J. Carbohydr. Res. 2006, 341, 1353−1362. (b) Stannard, K. A.; Collins, P. M.; Ito, K.; Sullivan, E. M.; Scott, S. A.; Gabutero, E.; Grice, I. D.; Low, P.; Nilsson, U. J.; Leffler, H.; Blanchard, H.; Ralph, S. J. Cancer Lett. 2010, 299, 95−110. (c) Sato, S.; Ito, Y.; Ogawa, T. Carbohydr. Res. 1986, 155, C1−5. (d) Sato, S.; Ito, Y.; Ogawa, T. Tetrahedron Lett. 1988, 29, 5267−5270. (13) (a) Pozsgay, V.; Nánási, P.; Neszmélyi, A. Carbohydr. Res. 1979, 75, 310−313. (b) Rychener, M.; Bigler, P.; Pfander, H. Helv. Chim. Acta 1984, 67, 378−385. (c) Gómez de Segura, A.; Alcalde, M.; Bernabé, M.; Ballesteros, A.; Plou, F. J. J. Biotechnol. 2006, 124, 439− 445. (d) Brissonnet, Y.; Ladevèze, S.; Tezé, D.; Fabre, E.; Deniaud, D.; Daligault, F.; Tellier, C.; Š esták, S.; Remaud-Simeon, M.; PotockiVeronese, G.; Gouin, S. G. Bioconjugate Chem. 2015, 26, 766−772. (e) Ahrazem, O.; Rubio-Moraga, A.; Jimeno, M.; Gómez-Gómez, L. Front. Plant Sci. 2015, 6, 971−985. (14) (a) Wang, P.; Zhu, J.; Yuan, Y.; Danishefsky, S. J. J. Am. Chem. Soc. 2009, 131, 16669−16671. (b) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J. Am. Chem. Soc. 1988, 110, 5583− 5584. (c) Deng, S.; Gangadharmath, U.; Chang, C.-W. T. J. Org. Chem. 2006, 71, 5179−5185. (15) We recently developed stereoselective α- and β-mannosylation using a TAB-modified donor: Ding, F.; Ishiwata, A.; Ito, Y. Submitted.
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DOI: 10.1021/acs.orglett.8b01922 Org. Lett. XXXX, XXX, XXX−XXX
