(Click Chemistry) - tcichemicals.com

1 (Click Chemistry) . - 1,2,3- .. 2001 K. B. Sharpless .. 2 .. a) HIV 3). Whiting Sharpless HIV . 1. HIV . 2.. 3.. 4. (1) K i = 8 nM .. 5.. O. R HN O. O. (36 Alkynes) Ph R= N Cl HN Ph O CuSO4, Cu N. N. 1961 R. Huisgen Ph Ph t BuOH / H2O (1 : 1), N. N3 N K i = 23 nM (minimum). 50 C , 5 days [3+2] R. 1) 1,2,3- . O. 1,2,3- HN O. Ph (CH2O)n N. Ph N CH2OH.. n BuLi, THF, -78 C to 0 C . N. N N K i = 8 nM. Cl 1. Metal (cat.). Ligand N N. +. + N. N N N b) 4). Dondoni 1,2,3- . C - . (I) (2a-f) 2a-f . [(1- -1 H- . 1,2,3- -4- ) ] (TBTA) (T2993) (n = 4) 2c . (n = 6) 2d IC50 = mM . 2) mM . HO N3 N3. H3C OBn OBn OBn OBn O O O O. BnO BnO BnO BnO. N N BnO BnO BnO BnO. N. OMOM. N N OH. N. N N. N. N. H3C OH. O. HO. HO. N. T2993 (TBTA) N N. OH. O. HO. HO. n N. 2a (n = 0). 100% N N. OH. O. 2b (n = 2). HO 2c (n = 4). HO. 2d (n = 6).. 2e (n = 8). OH 2f (n = 14).. 2.. Kang . Jin . (3) (4) 3 (I) .. 5) . N-(1R,8S,9S)- [ ] -4- -9- . -1,8- -3,6- . (BCN- ) (B4062) . N3 N3 + R O(H2C)6O2C CO2(CH2)6O R.

2 C8H17 C8H17. B4062 . 9 . CuSO45H2O, Et3N N3 N N. N. (I) . Na-L-ascorbate 14) B4062 . C8H17 C8H17. THF, 35 C , 48 h n R O(H2C)6O2C CO2(CH2)6O R Strain-promoted alkyne-azide cycloaddition SPAAC 15). 3 (R = OMe) Strain-promoted alkyne- 4 (R = CN). nitrone cycloaddition SPANC 16) .. O. ( )6) H H. O. O + N O C Fluorophore O NH2. O N O O.. H. B4062. DNA RNA . (capsid) . 60 . Finn Sharpless H H. O. H. O N Fluorophore (cowpea mosaic virus) O N. H. O. O. 9.. N. N. N. N N N.. strain-promoted H H. H H alkyne-azide cycloaddition O. HO O O H. N N N3 (SPAAC) O N Fluorophore O N O. H. O O 60 O. CO2H. Virus capsid 5. CH3. N. H H O. N N CH3. O N R N. O O 60 H O. 7 (R = -C CH ). 6. 8 (R = -CH2CH2N3) H H. strain-promoted O. alkyne-nitrone cycloaddition H. O N Fluorophore (SPANC) O N O. H. N O. N. O. Cu(I) N. + HN. 5 7. Dy e n 5,6,11,12- [a,e] . N. N. N (T3241) 17) . Cu(I).. + O. 6 8. HN. Dy e n . 18) .. 7) 8) . 9) 10) 11) . 12) DNA 13) .. 3.. Metal-Free Double-click Rection ( ).

3 N.. N N. Ph . Ph E0467 . N N. Ph N3. N (Y. 60%) . + . MeOH, rt, 70 min N. T3241 N N. Ph O O. HC C I BF4 R. R. Base C CH. +. Ph N N O O. N (Y. 38%). E0467. ex.) O O. CH3. C CH C CH. O. O Y. 74% O Y. 93%.. (1- -2- ) . (D3546) Bestmann . 21,22) .. D3546 . -Bestmann .. 22). 1 . 2- -1,3- . (A2457) O O. OCH3. CH3. P. OCH3 R CHO Product Yield (%). (DSC 200 N2. Cl CHO Cl 97. D3546.. A2457 74. OHC CHO. 19) R CHO + D3546. K2CO3. 80. R S CHO S. MeOH, rt, 4-16 h CH3. N. PF6. DMAP 23). N N3. + R NH2 R N3 2 . CH3 CH2Cl2. A2457. CHO. A2457 (eq.) Yield (%). D3546 ( eq.). Entry R DMAP (eq.) Temp. Time (h). CO2Me K2CO3 ( eq.) CO2Me 1 Ph rt 87. MeOH, rt, 2 h 2 4-MeC6H4 rt 94. 3 4-AcC6H4 3 50 C 5 83 OTIPS OTIPS Yield 84%. 4 4-O2NC6H4 2 3 50 C 4 61. 5 1-naphthyl 50 C 92. 6 PhCH2CH2 5a) rt 74. 7 1-adamantyl rt 71. a) Et3N is used instead of DMAP.. 1) R. Huisgen, Int. , 2, 565. 2) Q. Wang, T. R. Chan, R. Hilgraf, V. V. Fokin, K. B. Sharpless, M. G. Finn, J. Am. Chem.

4 Soc. 2003, 125, 3192; T. R. Chan, R. Hilgraf, K. B. Sharpless, V. V. Fokin, Org. Lett. 2004, 6, 2853. 3) M. Whiting, J. C. Tripp, Y. -C. Lin, W. Lindstrom, A. J. Olson, J. H. Elder, K. B. ( ) Sharpless, V. V. Fokin, J. Med. Chem. 2006, 49, 7697. (E0467) 4) M. L. Conte, A. Marra, A. Chambery, S. S. Gurcha, G. S. Besra, A. Dondoni, J. Org. Chem. 2010, 75, 6326. - 20) 5) J. S. Park, Y. H. Kim, M. Song, C. -H. Kim, M. A. Karim, J. W. Lee, Y. -S. Gal, P.. 4.. Kumar, S. -W. Kang, S. -H., Macromol. Chem. Phys. 2010, 211, 2464. 49, 9422. 6) Q. Wang, T. R. Chan, R. Hilgraf, V. V. Fokin, K. B. Sharpless, M. G. Finn, J. Am. 15) N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc. 2004, 126, 15046. Chem. Soc. 2003, 125, 3192. 16) X. Ning, R. P. Temming, J. Dommerholt, J. Guo, D. B. Ania, M. F. Debets, M. A. 7) M. Malkoch, K. Schleicher, E. Drockenmuller, C. J. Hawker, T. P. Russell, P. Wu, Wolfert, Boons, F. L. van Delft, Angew. Chem. Int. Ed. 2010, 49, 3065.

5 V. V. Fokin, Macromolecules, 2005, 38, 3663. 17) H. N. C. Wong, P. J. Garratt, F. Sondheimer, J. Am. Chem. Soc. 1974, 96, 5604. 8) G. Franc, A. Kakkar, Chem. Commun. 2008, 5267. 18) I. Kii, A. Shiraishi, T. Hiramatsu, T. Matsushita, H. Uekusa, S. Yoshida, M. 9) S. P. Bew, R. A. Brimage, N. L. Hermite, S. V. Sharma, Org. Lett. 2007, 9, 3713. Yamamoto, A. Kudo, M. Hagiwara, T. Hosoya, Org. Biomol. Chem. 2010, 8, 10) W. R. Dichtel, O. S. Miljanic, J. M. Spruell, J. R. Heath, J. F. Stoddart, J. Am. Chem. 4051. Soc. 2006, 128, 10388. 19) M. Kitamura, M. Yano, N. Tashiro, S. Miyagawa, M. Sando, T. Okauchi, Eur. J. 11) O. S. Miljani , W. R. Dichtel, S. I. Khan, S. Mortezaei, J. R. Heath, J. F. Stoddart, Org. Chem. 2011, 458. J. Am. Chem. Soc. 2007, 129, 8236. 20) M. Ochiai, T. Ito, Y. Takaoka, Y. Masaki, M. Kunishima, S. Tani, Y. Nagao, J. Chem. 12) Y. H. Lau, P. J. Rutledge, M. Watkinson, M. H. Todd, Chem. Soc. Rev. 2011, 40, Soc. Chem. Commun. 1990, 118; , TCI , 1999, number 104, 2.

6 2848. 21) S. Ohira, Synth. , 19, 561. 13) G. A. Burley, J. Gierlich, M. R. Mofid, H. Nir, S. Tal, Y. Eichen, T. Carell, J. Am. 22) S. M ller, B. Liepold, G. J. Roth, H. J. Bestmann, Synlett 1996, 521. Chem. Soc. 2006, 128, 1398. 23) J. D. White, P. R. Blakemore, C. C. Browder, J. Hong, C. M. Lincoln, P. A. 14) J. Dommerholt, S. Schmidt, R. Temming, L. J. A. Hendriks, F. P. J. T. Rutjes, J. C. Nagomyy, L. A. Robarge, D. J. Wardrop, J. Am. Chem. Soc. 2001, 123, 8593. M. van Hest, D. J. Lefeber, P. Friedl, F. L. van Delft, Angew. Chem. Int. Ed. 2010, . 5.. 7 14. 7 14.. PEG . 14.. 9.. PEG .. A1540 5g 25g T1442 1g 5g T2666 1g 5g 25g O O. CH3 OCu CF3 S OCu O 2.. (CH3CN)4Cu BF4. Copper(I) Trifluoromethane- Tetrakis(acetonitrile)copper(I). Copper(I) Acetate sulfonate Benzene Complex Tetrafluoroborate [598-54-9] [42152-46-5] [15418-29-8]. T2665 5g C3042 200mg 1g T2993 1g 5g T3170 200mg 1g B0989 1g N N. N. NaO3S SO3Na Ru HN. Cl Cl N N N. Ru Ru N. N N. Cl Cl N N N.

7 XH2O. (CH3CN)4Cu PF6 Ru N. NH. N N. H N N. Tetrakis(acetonitrile)- Chloro(pentamethylcyclo- Tris[(1-benzyl-1H-1,2,3- Bathophenanthrolinedisulfonic copper(I) Hexafluoro- pentadienyl)ruthenium(II) triazol-4-yl)methyl]amine Tris(2-benzimidazolylmethyl) Acid Disodium Salt Hydrate phosphate [64443-05-6] Tetramer [113860-07-4] (TBTA) [510758-28-8] amine [64019-57-4] [53744-42-6]. A1786 5g 25g 100g A0930 5g 25g O. SO2N3. C OH. O. NH C CH3 N3. 4-Acetamidobenzenesulfonyl 4-Azidobenzoic Acid Azide [2158-14-7] [6427-66-3]. A2474 100mg A0971 5g A2758 200mg A2052 1g 5g A1341 5g O. S CH2N3. N3 CH3. N3 HN. O O O. O O HO O N. CH3 CH3 N3 CH CH C H. CH3 O O CH3 O. O O. 2-Azido-1,3-bis[(2,2-dimethyl- N3. 1,3-dioxan-5-yl)oxy]propane 4-Azidocinnamaldehyde 4-Azidocoumarin 3'-Azido-3'-deoxythymidine Azidomethyl Phenyl [1392500-07-0] [22736-78-3] [42373-56-8] [30516-87-1] Sulfide [77422-70-9]. A2738 100mg A2524 100mg A2290 100mg 1g A2674 1g A2729 200mg O O. O. C OH C OH.

8 HN NH. OH F F O. H H O. N3 NH2. S (CH2)4 N N3 N3 OH. H F F. N3 N3. 3-Azidopropylamine N-(3-Azidopropyl)- 4-Azidosalicylic Acid 4-Azido-2,3,5,6-tetrafluoro- 5-Azidovaleric Acid [88192-19-2] biotinamide [908007-17-0] [66761-27-1] benzoic Acid [122590-77-6] [79583-98-5]. B1110 5g 25g B3693 100mg B3694 100mg B3790 10mg D1606 25g OCH3 OCH3. N3CH2 O N3CH2 O. O CH3 CH3. N3 HC CH N3 N3 N3 CH CH N3. CH3 CH3 H O OH. N3CH2 O N3CH2 O N. S. S. N .4H2O. OCH3 OCH3 H SO3Na NaO3S. OH O. N3. 2,6-Bis(4-azidobenzylidene)- (2R,3R,5S,6S)-5,6- (2S,3S,5R,6R)-5,6- Disodium cyclohexanone (wetted with ca. Bis(azidomethyl)-2,3- Bis(azidomethyl)-2,3- Bis[2-(4-azidosalicyl- 4,4'-Diazidostilbene-2,2'- 30% Water, containing 25g on a dimethoxy-2,3-dimethyl- dimethoxy-2,3-dimethyl- amido)ethyl] Disulfide disulfonate Tetrahydrate dry weight basis) [20237-98-3] 1,4-dioxane [832117-79-0] 1,4-dioxane [1585236-34-5] [199804-21-2] [2718-90-3]. D2580 25g S0860 10mg S0952 200mg 1g T1184 1g 5g A2942 25mg 100mg O.

9 F F O. N3 O O CH3 HN. O. N3 C O N CH3 Si CH2N3. C O N HO O N. F F O CH3 O. NO2 O. Dodecylbenzenesulfonyl N-Succinimidyl 4-Azido- Azide (soft type) (mixture) N-Succinimidyl 5-Azido-2- 2,3,5,6-tetrafluorobenzoate Trimethylsilylmethyl Azide OH N3. [79791-38-1] nitrobenzoate [60117-35-3] [126695-58-7] [87576-94-1] N3-dU [26929-65-7]. A3020 250mg A3023 250mg A2791 200mg 1g A2523 100mg CH2N3. O. O O. PEG . HN NH. H H O. N3 N3 O O. OH OH S (CH2)4 N. H. O N3. HN HN. Fmoc Fmoc N-[2-[2-[2-(2-Azidoethoxy)- 4-Azido-N-Fmoc-L- 6-Azido-N-Fmoc- L- 1-(Azidomethyl)pyrene ethoxy]ethoxy]ethyl]- homoalanine [942518-20-9] norleucine [159610-89-6] [1006061-57-9] biotinamide [875770-34-6].. 7.. A2727 25mg 100mg A2388 25mg A2500 100mg A2728 25mg 100mg A2363 200mg 1g 5g O. O. O N3 O O O O O. CH3 N3 N3 N O O OH CH3 N3 N3 O NH2. 8 O O 4. 4. O. 25-Azido-2,5,8,11,14,17,20,23- 14-Azido-3,6,9,12- 13-Azido-2,5,8,11- 11-Azido-3,6,9- octaoxapentacosane Azido-PEG4-NHS Ester tetraoxatetradecanol tetraoxatridecane trioxaundecan-1-amine [869718-80-9] [944251-24-5] [86770-68-5] [606130-90-9] [134179-38-7].

10 A2293 1g A2294 100mg A1812 1g A1813 1g Ph O Ph O. O O. O O.. O. O N3 BnO N3. O O O O. N3 O OH N3 O OH NHAc NHAc 2-Acetamido-3-O-benzyl- 11-Azido-3,6,9- 11-Azido-3,6,9- 2-Acetamido-3-O-allyl-4,6- 4,6-O-benzylidene-2-deoxy- trioxaundecanoic Acid trioxaundecanol O-benzylidene-2-deoxy-b- b-D -glucopyranosyl Azide [172531-37-2] [86770-67-4] D -glucopyranosyl Azide [80887-27-0]. A1811 1g 5g A1616 1g 5g A1678 1g 5g G0257 1g 5g A2627 . Ph OAc OBn O AcO HO. O O O OAc OH. O AcO BnO O. HO N3 AcO N3 BnO N3 O. AcO O N3. O O HO O. NHAc AcHN AcHN AcO. N3. AcHN. 2-Acetamido-4,6- 2-Acetamido-3,4,6-tri- 2-Acetamido-3,4,6-tri- 2-[2-(2-Azidoethoxy)ethoxy]- O-benzylidene-2-deoxy-b- O-acetyl-2-deoxy-b- O-benzyl-2-deoxy-b- ethyl 2,3,4,6-Tetra-O-acetyl- 2-Azidoethyl 2-Acetamido-2- D -glucopyranosyl Azide D -glucopyranosyl Azide D -glucopyranosyl Azide D -galactopyranoside deoxy- -D -galactopyranoside [168397-51-1] [6205-69-2] [214467-60-4] [381716-33-2] [142072-15-9].