银介导的N-芳基丙烯酰胺串联环化反应研究进展

doi:10.6023/cjoc202211003

摘要/Abstract

作为明星分子, N-芳基丙烯酰胺可发生自由基加成串联环化反应, 从而高效构建C(3)-二取代吲哚-2-酮骨架. 吲哚-2-酮类化合物是一类重要的杂环化合物, 具有广泛的生物活性, 一直是有机化学和药物化学领域的研究热点. 银催化剂具有独特的催化活性, 毒性低, 在有机合成中的应用愈加广泛. 从不同的自由基前体及成键类型(C—C、C—N、 C—P、C—S)出发, 对银介导的N-芳基丙烯酰胺串联环化反应研究进展进行了综述, 并对代表性底物及反应机理进行了归纳和讨论.

关键词: 银介导反应, N-芳基丙烯酰胺, 串联环化反应, C(3)-二取代吲哚-2-酮

As a star molecule, N-arylacrylamides can undergo tandem radical addition/cyclization to efficiently construct C(3)-disubstituted indolin-2-ones. Indolin-2-ones are a class of important heterocyclic compounds with a wide range of biological activities, and the synthesis of which has been a research hotspot in the field of organic chemistry and medicinal chemistry. Silver catalysts are low in toxicity, and have unique catalytic activities, which are widely used in organic synthesis. In this paper, starting from different radical precursors and bond types (C—C, C—N, C—P, C—S), the research progress of silver-mediated synthesis of C(3)-disubstituted indolin-2-ones via tandem radical addition/cyclization of N-arylacrylamides is reviewed, and the representative substrates and reaction mechanisms are also summarized and discussed.

Key words: silver-mediated reaction, N-arylacrylamides, tandem cyclization, C(3)-disubstituted indolin-2-ones

引用此文

任志军, 罗维纬, 周俊. 银介导的N-芳基丙烯酰胺串联环化反应研究进展[J]. 有机化学, 2023, 43(6): 2026-2039.

Zhijun Ren, Weiwei Luo, Jun Zhou. Recent Progress in Silver-Mediated Tandem Cyclization of N-Arylacrylamides[J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 2026-2039.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 19

图1. 具有吲哚-2-酮骨架药物的部分示例

Figure 1. Some examples of drugs with an indolin-2-one backbone

图2. 毒扁豆碱及吡咯烷酮类药物

Figure 2. Physostigmine and pyrrolidone drugs

图式1. α-氧代羧酸的脱羧酰基/芳基化反应

Scheme 1. Decarboxylative acylarylation of α-oxocarboxylic acids

图式2. 草胺酸类化合物的脱羧酰基/芳基化反应

Scheme 2. Decarboxylative acylarylation of oxamic acids

图式3. 1,3-二羰基化合物的烷基/芳基化反应

Scheme 3. Alkyl/arylation of 1,3-dicarbonyl compounds

图式4. 环丙醇类化合物的烷基/芳基化反应

Scheme 4. Alkyl/arylation of cyclopropanols

图式5. 氨基酸类化合物的脱羧氨基烷基化反应

Scheme 5. Decarboxylative aminoalkylation of amino acids

图式6. 二氟乙酰胺类化合物的二氟甲基化反应

Scheme 6. Difluoromethylation of difluoroacetamides

图式7. 二氟乙酸酯类化合物的二氟甲基化反应

Scheme 7. Difluoromethylation of difluoroacetate compounds

图式8. 二氟芳基乙酸钾的二氟甲基化反应

Scheme 8. Difluoromethylation of potassium difluoroarylacetate

图式9. 二氟芳基乙酸的二氟甲基化反应

Scheme 9. Difluoromethylation of difluoroarylacetic acids

图式10. 银催化活性烯烃通过C—H键裂解的叠氮-碳环化反应

Scheme 10. Ag-promoted azido-carbocyclization of activated alkenes via C—H bond cleavage

图式11. 银催化N-芳基丙烯酰胺的叠氮化反应

Scheme 11. Silver-catalyzed azido reaction of N-arylacrylamides

图式12. 银促进N-芳基丙烯酰胺的硝化反应

Scheme 12. Silver-promoted nitration of N-arylacrylamides

图式13. 银催化N-芳基丙烯酰胺的硝化反应

Scheme 13. Silver-catalyzed nitration of N-arylacrylamides

图式14. 银催化N-芳基丙烯酰胺的膦酰化反应

Scheme 14. Silver-catalyzed phosphonylation of N-arylacryl- amides

图式15. 银促进丙烯磺酰胺类化合物的膦酰化/叠氮化反应

Scheme 15. Silver-promoted phosphonylation/azidization of acrylsulfonamides

图式16. 银促进N-芳基丙烯酰胺的三氟甲硫基化反应

Scheme 16. Silver-promoted trifluoromethylthiolation of N- arylacrylamides

图式17. 银促进N-芳基丙烯酰胺的硫氰化反应

Scheme 17. Silver-promoted thiocyanation of N-arylacrylamides

参考文献 47

[1]	Dalpozzo, R. Org. Chem. Front. 2017, 4, 2063. doi: 10.1039/C7QO00446J
[2]	Kaur, M.; Singh, M.; Chadha, N.; Silakari, O. Eur. J. Med. Chem. 2016, 123, 858. doi: 10.1016/j.ejmech.2016.08.011
[3]	Millemaggi, A.; Taylor, R.-J.-K. Eur. J. Org. Chem. 2010, 4527.
[4]	Ding, Z.; Zhou, M.; Zeng, C. Arch. Pharm. 2020, 353, 1900367. doi: 10.1002/ardp.v353.3
[5]	Luo, W.-M.; Yu, Q.-S.; Kulkarni, S.-S.; Parrish, D.-A.; Holloway, H.-W.; Tweedie, D.; Shafferman, A.; Lahiri, D.-K.; Brossi, A.; Greig, N.-H. J. Med. Chem. 2006, 49, 2174. doi: 10.1021/jm050578p
[6]	Yu, Q.-S.; Zhu, X.-X.; Holloway, H.-W.; Whittaker, N.-F.; Brossi, A.; Greig, N.-H. J. Med. Chem. 2002, 45, 3684. doi: 10.1021/jm010491d
[7]	Sumpter, W.-C. Chem. Rev. 1945, 37, 443. doi: 10.1021/cr60118a003
[8]	Yamamoto, K.; Qureshi, Z.; Tsoung, J.; Pisella, G.; Lautens, M. Org. Lett. 2016, 18, 4954. pmid: 27632781
[9]	Jang, Y.-J.; Larin, E.-M.; Lautens, M. Angew. Chem., Int. Ed. 2017, 56, 11927. doi: 10.1002/anie.201704922
[10]	(a) Rodríguez, J.-F.; Zhang, A.; Bajohr, J.; Whyte, A.; Mirabi, B.; Lautens, M. Angew. Chem., Int. Ed. 2021, 60, 18478. doi: 10.1002/anie.v60.34
	(b) Marchese, A.-D.; Wollenburg, M.; Mirabi, B.; Abel-Snape, X.; Whyte, A.; Glorius, F.; Lautens, M. ACS Catal. 2020, 10, 4780. doi: 10.1021/acscatal.0c00841
[11]	Sperger, T.; Le, C.-M.; Lautens, M.; Schoenebeck, F. Chem. Sci. 2017, 8, 2914. doi: 10.1039/C6SC05001H
[12]	Marchese, A.-D.; Larin, E.-M.; Mirabi, B.; Lautens, M. Acc. Chem. Res. 2020, 53, 1605. doi: 10.1021/acs.accounts.0c00297
[13]	(a) Liu, Y.-J.; Lin, L.-Q.; Han, Y.-H.; Zhang, X. Chin. J. Org. Chem. 2019, 39, 2705. (in Chinese)
	(刘颖杰, 林立青, 韩莹徽, 张鑫, 有机化学, 2019, 39, 2705.) doi: 10.6023/cjoc201904014
	(b) Wang, L.-L.; Zhang, Z.-Y.; Han, H.-B.; Liu, X.-L.; Bu, Z.-W.; Wang, Q.-L. Chin. J. Org. Chem. 2021, 41, 12. (in Chinese) doi: 10.6023/cjoc202007045
	(王乐乐, 张子莹, 韩华彬, 刘雄利, 卜战伟, 王琪琳, 有机化学, 2021, 41, 12.) doi: 10.6023/cjoc202007045
	(c) Abdukader, A.; Zhang, Y.-H.; Zhang, Z.-P.; Liu, C.-J. Chin. J. Org. Chem. 2016, 36, 875. (in Chinese)
	(阿布力米提•阿布都卡德尔, 张永红, 张增鹏, 刘晨江有机化学, 2016, 36, 875.)
	(d) Zhao, Y.; Lv, Y.; Xia, W. Chem. Rec. 2019, 19, 424. doi: 10.1002/tcr.v19.2-3
	(e) Singh, J.; Sharma, A. Adv. Synth. Catal. 2021, 363, 4284. doi: 10.1002/adsc.v363.18
[14]	(a) Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108, 3149. doi: 10.1021/cr078365q pmid: 18637695
	(b) Álvarez-Corral, M.; Muñoz-Dorado, M.; Rodríguez-Garcí, R. Chem. Rev. 2008, 108, 3174. doi: 10.1021/cr078361l pmid: 18637695
	(c) Naodovic, M.; Yamamoto, H. Chem. Rev. 2008, 108, 3132. doi: 10.1021/cr068413r pmid: 18637695
	(d) Fang, G.-C.; Cong, X.-F.; Zanoni, G.; Liu, Q.; Bi, X-H. Adv. Synth. Catal. 2017, 359, 1422. doi: 10.1002/adsc.v359.9 pmid: 18637695
[15]	(a) Mai, W.-P.; Wang, J.-T.; Yang, L.-R.; Yuan, J.-W.; Mao, P.; Xiao, Y.-M.; Qu, L.-B. Chin. J. Org. Chem. 2014, 34, 1958. (in Chinese) doi: 10.6023/cjoc201405006
	(买文鹏, 王继涛, 杨亮茹, 袁金伟, 毛璞, 肖咏梅, 屈凌波, 有机化学, 2014, 34, 1958.) doi: 10.6023/cjoc201405006
	(b) Chen, J.-R.; Yu, X.-Y.; Xiao, W.-J. Synthesis 2015, 47, 604. doi: 10.1055/s-00000084
	(c) Song, R.-J.; Liu, Y; Xie, Y.-X.; Li, J.-H. Synthesis 2015, 47, 1195. doi: 10.1055/s-00000084
	(d) Li, C.-C.; Yang, S.-D. Org. Biomol. Chem. 2016, 14, 4365. doi: 10.1039/C6OB00554C
	(e) Wu, Y.-C.; Xiao, Y.-T.; Yang, Y.-Z.; Song, R.-J.; Li, J.-H.; ChemCatChem 2020, 12, 5312. doi: 10.1002/cctc.v12.21
[16]	For recent reviews, see: (a) Baudoin, O. Angew. Chem. 2007, 119, 1395; Angew. Chem., Int. Ed. 2007, 46, 1373. doi: 10.1002/(ISSN)1521-3757 pmid: 21792454
	(b) Gooßen, L.-J.; Rodríguez, N.; Gooßen, K. Angew. Chem., Int. Ed. 2008, 47, 3100. doi: 10.1002/(ISSN)1521-3773 pmid: 21792454
	(c) Satoh, T.; Miura, M. Synthesis 2010, 3395. pmid: 21792454
	(d) Rodríguez, N.; Gooßen, L.-J. Chem. Soc. Rev. 2011, 40, 5030. doi: 10.1039/c1cs15093f pmid: 21792454
	(e) Shang, R.; Liu, L. Sci. China: Chem. 2011, 54,1670. pmid: 21792454
	(f) Dzik, W.-I.; Lange, P.-P.; Gooßen, L.-J. Chem. Sci. 2012, 3, 2671. doi: 10.1039/c2sc20312j pmid: 21792454
	(g) Cornella, J.; Larrosa, I. Synthesis 2012, 653. pmid: 21792454
[17]	Wang, H.; Guo, L.-N.; Duan, X.-H. Adv. Synth. Catal. 2013, 355, 2222. doi: 10.1002/adsc.201300468
[18]	Bai, Q.-F.; Jin, C.-G.; He, J.-Y.; Feng, G.-F. Org. Lett. 2018, 20, 2172. doi: 10.1021/acs.orglett.8b00449
[19]	Gao, Q.-S.; Jin, Q.; Chen, Y.; Sun, J.; Zhou, M.-D. Chin. J. Org. Chem. 2022, 42, 257. (in Chinese) doi: 10.6023/cjoc202105025
	(高启升, 荆祺, 陈阳, 孙京, 周明东, 有机化学, 2022, 42, 257.) doi: 10.6023/cjoc202105025
[20]	Beck, E.; Grimster, N.; Hatley, R.; Gaunt, M. J. Am. Chem. Soc. 2006, 128, 2528. doi: 10.1021/ja058141u
[21]	Wang, H.; Guo, L.-N.; Duan, X.-H. Chem. Commun. 2013, 49, 10370. doi: 10.1039/C3CC46114A
[22]	Li, Y.-H.; Wang, J.-J.; Wei, X.-H.; Yang, S.-D. Chin. J. Org. Chem. 2015, 35, 638. (in Chinese) doi: 10.6023/cjoc201412030
	(李永红, 王君姣, 魏小红, 杨尚东, 有机化学, 2015, 35, 638.) doi: 10.6023/cjoc201412030
[23]	Kanyiva, K.-S.; Makino, S.; Shibata, T. Chem. Asian J. 2018, 13, 496. doi: 10.1002/asia.v13.5
[24]	For selected book chapters and reviews, see: (a) Wang, J.; Sánchez-Rosellò, M.; Aceña, J.-L.; Delpozo, C.; Sorochinsky, A.-E.; Fustero, S.; Soloshonok, V.-A.; Liu, H. Chem. Rev. 2014, 114, 2432. doi: 10.1021/cr4002879 pmid: 26756377
	(b) Gillis, E.-P.; Eastman, K.-J.; Hill, M.-D.; Donnelly, D.-J.; Meanwell, N.-A. J. Med. Chem. 2015, 58, 8315. doi: 10.1021/acs.jmedchem.5b00258 pmid: 26756377
	(c) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J.-L.; Soloshonok, V.-A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422. doi: 10.1021/acs.chemrev.5b00392 pmid: 26756377
[25]	(a) Blackburn, G.-M.; England, D.-A.; Kolkmann, F. J. Chem. Soc., Chem. Commun. 1981, 930.
	(b) Xu, Y.; Aoki, J.; Shimizu, K.; Umezu-Goto, M.; Hama, K.; Takanezawa, Y.; Yu, S.; Mills, G.-B.; Arai, H.; Qian, L.; Prestwich, G.-D. J. Med. Chem. 2005, 48, 3319. doi: 10.1021/jm049186t
	(c) Meanwell, N.-A. J. Med. Chem. 2011, 54, 2529. doi: 10.1021/jm1013693
[26]	Wang, C.; Chen, Q.; Guo, Q.-P.; Liu, H.; Xu, Z.-Q.; Liu, Y.-B.; Wang, M.-R.; Wang, R. J. Org. Chem. 2016, 81, 5782. doi: 10.1021/acs.joc.6b01013
[27]	Wang, X.-L.; Wan, W.; Chen, Y.-R.; Li, J.-L.; Jiang, H.-Z.; Wang, Y.; Deng, H.-M.; Hao, J. Eur. J. Org. Chem. 2016, 3773.
[28]	Wan, W.; Li, J.-L.; Ma, G.-B.; Chen, Y.-R.; Jiang, H.-Z.; Deng, H.-M.; Hao, J. Org. Biomol. Chem. 2017, 15, 5308. doi: 10.1039/C7OB00955K
[29]	(a) Middleton, W.-J.; Bingham, E.-M. J. Org. Chem. 1980, 45, 2883. doi: 10.1021/jo01302a025 pmid: 21125999
	(b) Hagele, G.; Haas, A. J. Fluorine Chem. 1996, 76, 15. doi: 10.1016/0022-1139(95)03346-7 pmid: 21125999
	(c) Lal, G.-S.; Pez, G.-P.; Pesaresi, R.-J.; Prozonic, F.-M.; Cheng, H. J. Org. Chem. 1999, 64, 7048. doi: 10.1021/jo990566+ pmid: 21125999
	(d) Singh, R.-P.; Majumder, U.; Shreeve, J.-M. J. Org. Chem. 2001, 66, 6263. pmid: 21125999
	(e) Umemoto, T.; Singh, R.-P.; Xu, Y.; Saito, N. J. Am. Chem. Soc. 2010, 132, 18199. doi: 10.1021/ja106343h pmid: 21125999
[30]	Li, Y.-L.; Wang, J.-B.; Wang, X.-L.; Cao, Y.; Deng, J. Eur. J. Org. Chem. 2017, 6052.
[31]	For some examples, see: (a) Saha, G.; Khanapure, S.-P.; Powell, W.-S.; Rokach, J. Tetrahedron Lett. 2000, 41,6313. doi: 10.1016/S0040-4039(00)01064-9 pmid: 19737023
	(b) Kim, S.; Adiyaman, Y.; Saha, G.; Powell, W.-S.; Rokach, J. Tetrahedron Lett. 2001, 42,4445. doi: 10.1016/S0040-4039(01)00699-2 pmid: 19737023
	(c) Pinney, K.-G.; Mejia, M.-P.; Villalobos, V.-M.; Rosenquist, B.-E.; Petit, G.-R.; Verdier-Pinard, P.; Hamel, E. Bioorg. Med. Chem. 2000, 8, 2417. doi: 10.1016/S0968-0896(00)00176-0 pmid: 19737023
	(d) Dutta, A.-K.; Fei, X.-S.; Vaughan, R.-A.; Gaffaney, J.-D.; Wang, N.-N.; Lever, J.-R.; Reith, M.-E. Life Sci. 2001, 68, 1839. pmid: 19737023
	(e) Hennessy, E.-T.; Betley, T.-A. Science 2013, 340, 591. doi: 10.1126/science.1233701 pmid: 19737023
	For some reviews, see: (f) Gramlich, E.-M.-P.; Wirges, C.-T.; Manetto, A.; Carell, T. Angew. Chem., Int. Ed. 2008, 47, 8350. doi: 10.1002/anie.v47:44 pmid: 19737023
	(g) Amblard, F.; Cho, J.-H.; Schinazi, R.-F. Chem. Rev. 2009, 109, 4207. doi: 10.1021/cr9001462 pmid: 19737023
	(h) Sletten, E.-M.; Bertozzi, C.-R. Acc. Chem. Res. 2011, 44, 666. doi: 10.1021/ar200148z pmid: 19737023
	(i) Schilling, C.-I.; Jung, N.; Biskup, M.; Schepers, U.; Bräse, S. Chem. Soc. Rev. 2011, 40, 4840. doi: 10.1039/c0cs00123f pmid: 19737023
	(j) Huryn, D.-M.; Okabe, M. Chem. Rev. 1992, 92, 1745. doi: 10.1021/cr00016a004 pmid: 19737023
[32]	For some general reviews, see: (a) Chiba, S. Synlett 2012, 21 pmid: 20617243
	(b) Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem. 2005, 117, 5320; Angew. Chem., Int. Ed. 2005, 44, 5188. doi: 10.1002/(ISSN)1521-3757 pmid: 20617243
	(c) Driver, T.-G. Org. Biomol. Chem. 2010, 8, 3831. doi: 10.1039/c005219c pmid: 20617243
	(d) Minozzi, M.; Nanni, D.; Spagnolo, P. Chem. Eur. J. 2009, 15, 7830. doi: 10.1002/chem.v15:32 pmid: 20617243
[33]	Yuan, Y.-Z.; Shen, T.; Wang, K.; Jiao, N. Chem. Asian J. 2013, 8, 2932. doi: 10.1002/asia.v8.12
[34]	Wei, X.-H.; Li, Y.-M.; Zhou, A.-X.; Yang, T.-T.; Yang, S.-D. Org. Lett. 2013, 15, 4158. doi: 10.1021/ol402138y
[35]	Barrett, A.-G.-M.; Graboski, G.-G. Chem. Rev. 1986, 86, 751. doi: 10.1021/cr00075a002
[36]	Li, Y.-M.; Shen, Y.-H.; Chang, K.-J.; Yang, S.-D. Tetrahedron Lett. 2014, 55, 2119. doi: 10.1016/j.tetlet.2014.02.043
[37]	Wei, X.-H.; Wu, Q.-X.; Yang, S.-D. Synlett 2015, 26, 1417. doi: 10.1055/s-00000083
[38]	(a) Jeught, S.-V.; Stevens, C.-V. Chem. Rev. 2009, 109, 2672. doi: 10.1021/cr800315j pmid: 18831570
	(b) George, A.; Veis, A. Chem. Rev. 2008, 108, 4670. doi: 10.1021/cr0782729 pmid: 18831570
	(c) Bialy, L.; Waldmann, H. Angew. Chem., Int. Ed. 2005, 44, 3814. doi: 10.1002/(ISSN)1521-3773 pmid: 18831570
	(d) Alexandre, F.; Amador, A.; Bot, S.; Caillet, C.; Convard, T.; Jakubik, J.; Musiu, C.; Poddesu, B.; Vargiu, L.; Liuzzi, M.; Roland, A.; Seifer, M.; Standring, D.; Storer, R.; Dousson, C.-B. J. Med. Chem. 2011, 54, 392. doi: 10.1021/jm101142k pmid: 18831570
[39]	(a) Glueck, D.-S. Top. Organomet. Chem. 2010, 31, 65.
	(b) Baillie, C.; Xiao, J.-L. Curr. Org. Chem. 2003, 7, 477. doi: 10.2174/1385272033372761
	(c) Coudray, L.; Mxontchamp, J.-L. Eur. J. Org. Chem. 2008, 3601.
	(d) Leroux, F.; Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827. doi: 10.1021/cr040075b
	(e) Manteau, B.; Pazenok, S.; Vors, J.-P.; Leroux, F.-R. J. Fluorine Chem. 2010, 131, 140. doi: 10.1016/j.jfluchem.2009.09.009
[40]	Li, Y.-M.; Sun, M.; Wang, H.-L.; Tian, Q.-P.; Yang, S.-D. Angew. Chem., Int. Ed. 2013, 52, 3972. doi: 10.1002/anie.v52.14
[41]	Kong, W.-Q.; Merino, E.; Nevado, C. Angew. Chem., Int. Ed. 2014, 53, 5078. doi: 10.1002/anie.v53.20
[42]	(a) Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525. doi: 10.1021/cr60274a001
	(b) Yagupol’skii, L.-M.; Il'chenko, A.-Y.; Kondratenko, N.-V. Russ. Chem. Rev. 1974, 43, 32. doi: 10.1070/RC1974v043n01ABEH001787
	(c) Hansch, C.; Leo, A.; Taft, R.-W. Chem. Rev. 1991, 91, 165. doi: 10.1021/cr00002a004
	(d) Leroux, F.; Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827. doi: 10.1021/cr040075b
	(e) Manteau, B.; Pazenok, S.; Vors, J.-P.; Leroux, F.-R. J. Fluorine Chem. 2010, 131, 140. doi: 10.1016/j.jfluchem.2009.09.009
[43]	Yin, F.; Wang, X.-S. Org. Lett. 2014, 16, 1128. doi: 10.1021/ol403739w
[44]	Kong, D.-L.; Du, J.-X.; Chu, W.-M.; Ma, C.-Y.; Tao, J.-Y.; Feng, W.-H. Molecules 2018, 23, 2727. doi: 10.3390/molecules23102727
[45]	Zeng, Y.-F.; Tan, D.-H.; Chen, Y.; Lv, W.-X.; Liu, X.-G.; Li, Q.; Wang, H. Org. Chem. Front. 2015, 2, 1511. doi: 10.1039/C5QO00271K
[46]	Bruehlman, R.-J.; Verhoek, F.-H. J. Am. Chem. Soc. 1948, 70, 1401. doi: 10.1021/ja01184a033
[47]	Vosburgh, W.-C.; Cogswell, S.-A. J. Am. Chem. Soc. 1943, 65, 2412. doi: 10.1021/ja01252a049