우리는이 작업을 지원 스토니 브룩 뉴욕 주립 대학에서 관대 시작 자금을 인정합니다. 우리는 또한 Togni 시약 II의 합성에 대해 우리에게 TMSCF 3 시약을 제공 토소 F-테크, 주식 회사 감사합니다.

1. 전구체 제조 : 메틸 4- (N의 -hydroxyacetamido) 벤조 에이트 (1A)의 합성 <ol><li> 메틸 4- 니트로 벤조 에이트의 감소. <ol><li> 오븐 건조 된 250 ml의 2 차원에 메틸 4- 니트로 벤조 에이트 (27.6 밀리몰, 1.00 당량), 탄소 5 % 로듐의 159 mg의 로듐 (Rh / C, 0.300 몰 % RH) 및 자기 교반 바을 5.00 g을 넣고 (18 시간 동안 150 ℃에서 건조) 목 환저 플라스크. 참고 : 시약 주변 분위기에서 계량 할 수 있습니다. 그러나, 반응은 질소 분위기 하에서 수행 될 필요가있다. </li><li> 질소 / 진공 매니 폴드에 플라스크의 한 목을 연결하고 격막과 다른 목 모자. 세 진공 재충전 사이클을 수행 (즉, 플라스크 중 공기를 펌핑하고, 질소 가스로 인한 진공을 대체), 질소 가스와 함께 플라스크 내에서 공기를 교체. </li><li> 기밀 주사기를 사용하여 반응 플라스크에 138 ml의 무수 테트라 히드로 푸란 (THF, 0.200 M)를 첨가. 차가운 반응 믹스트를 저어15 분 동안 0 ℃에서 URE. </li><li> 기밀 주사기를 사용하여 0 ℃에서 반응 액에 히드라진 일 수화물 1.47 ㎖ (1.52 g, 30.4 밀리몰, 1.20 당량)를 적가. 박층 크로마토 그래피 (T​​LC)를 사용하여 반응을 모니터한다. 헥산을 사용하여 에틸 아세테이트 (EtOAc)에 (4 : 1 V / V, R의 F = 0.23)을 전개 용매로 TLC를 개발. </li><li> 메틸 4- 니트로 벤조 에이트가 완전히 소모되면, 진공 여과를 사용하여 부 흐너 깔때기를 프릿 60 ㎖ 중의 규조토의 짧은 패드 (즉, 셀 라이트, 5g)을 통하여 반응 혼합물을 필터. EtOAc로 필터 (20 ㎖ × 3 회)를 씻으십시오. 추가의 정제없이 직접 사용되는 조 메틸 4- (N의 -hydroxyamino) 벤조 에이트를 수득 회전 증발기로 감압 여과 액을 농축시켰다. </li></ol></li><li> 메틸 4- (N의 -hydroxyamino) 벤조산 아세틸 보호 <ol><li> 중탄산 나트륨 2.55 g을 추가 (의 NaHCO3, 30.4 밀리몰, 1.20 당량), 모든 조질이전 단계에서 수득 된 메틸 4- (N의 -hydroxyamino) 벤조 에이트, 및 오븐 건조 된 500㎖의 두 구 둥근 바닥 플라스크에 교반 바. </li><li> 격막 하나의 목을 모자와 질소 / 진공 매니 폴드에 다른 목을 연결합니다. 플라스크 내를 질소 가스로 공기를 대체하기 위해 세 진공 재충전 사이클을 수행한다. </li><li> 기밀 주사기를 사용하여 반응 플라스크에 138 ml의 무수을 디 에틸 에테르 (ET 2 O, 0.200 M)를 첨가. 냉각시키고 15 분 동안 0 ℃에서 반응 혼합물을 교반한다. </li><li> 무수을 Et2O (138 ㎖, 0.220 M)을 (2.17 ㎖, 2.39 g, 30.4 밀리몰, 1.20 당량), 아세틸 클로라이드의 용액을 제조 하였다. 10.0 ㎖ / 시간의 속도로 시린지 펌프를 이용하여 0 ℃에서 반응 혼합물에 용액을 첨가. </li><li> 첨가의 마지막에, 규조토의 짧은 패드를 ​​통해 반응 혼합물을 필터링 (즉, 셀 라이트, 5g) 60 ㎖ 중의 진공 여과를 사용하여 부 흐너 깔때기를 프릿. EtOAc로 필터 (20 ㎖ × 3 회)를 씻으십시오. 집중회전 증발기를 사용하여 진공 여과. </li><li> 헥산으로 플래쉬 컬럼 크로마토 그래피 (35) 용리와 조질 생성물을 정제 : EtOAc로를 (4 : 1 내지 1 : 1 (V / V)) (R의 F = 0.13, 헥산 :을 EtOAc (4 : 1 (V / V))로 5.31을 수득 밝은 황색 고체 (25.4 밀리몰, 수율 92 %)로서 메틸 4- (N의 -hydroxyacetamido) 안식향산의 g. </li></ol></li></ol> 벤조 에이트 (2A) - 메틸 4- ((트리 플루오 로메 톡시) 아세트 N) 2. 합성 <ol><li> 메틸 4- (N의 -hydroxyacetamido) 벤조 에이트 (1A) (9.56 밀리몰, 1.00 당량) 2.00 g, 세슘 2 CO 3의 311 mg의 (0.956 밀리몰, 10.0 몰 %), Togni 시약 II의 3.63 g (11.5 밀리몰 추가 1.20 당량), 및 글로브 박스 (질소 분위기 안에서 오븐 - 건조 된 250 mL의 둥근 바닥 플라스크에 자기 교반 바). 주 :이 반응은 또한 글로브 박스 밖에서 슈렌 기법을 사용하여 수행 될 수있다. 주의 : 순수 Togni 시약 II는 충격과 마찰에 민감한, 불꽃입니다S는, 불꽃 및 / 또는 그라인딩을 피해야한다. 부드럽고 광택이 도구는 조작을 위해 사용되어야한다. 또한, 반응 혼합물 안전 실드 뒤에 교반한다. 36 </li><li> 반응 플라스크에 건조 및 탈기 클로로포름 95.6 ㎖ (클로로포름, 0.100 M)를 첨가. </li><li> 중격 플라스크 캡 내부 또는 16 시간 동안 글러브 박스의 외부에 N 2 분위기 하에서 23 ℃에서 반응 혼합물을 저어. </li><li> 임의의 고체 잔류 물을 제거하기 위해 필터 깔때기를 통해 반응 혼합물을 필터. 회전 증발기를 사용하여 진공 하에서 여과 액을 농축시켰다. </li><li> 디클로로 메탄 (CH 2 CL 2) 플래시 칼럼 크로마토 그래피는 헥산으로 용출하여 조질 생성물을 정제 (7 : 0~3 : 1 (V / V)) (R의 F = 0.44 (CH 2 CL (2))을 수득 (- (트리 플루오 로메 톡시) 아세트 N) 벤조 에이트 (9.05 밀리몰, 수율 95 %)의 4- 메틸 2.51 g. 참고 : Togni 시약 II는 준비 협정이다문헌 절차 37, -35 ℃에서 냉동 글로브 박스에 저장하기에 보내고 장기간에 걸쳐 그 품질을 유지한다. 이 반응은 산소에 민감하다. 모든 시약을 실온에서 주위 분위기하에 칭량 할 수 있지만, 반응 플라스크로부터 모든 산소를 제거하여 매우 중요하다. 건조 및 동결 - 펌프 - 해동 절차의 3주기를 수행 한 다음, 질소 분위기 하에서 2 CAH에서 증류에 의해 제조된다 클로로포름 탈기. </li></ol> 3. 메틸의 합성 4- 아세트 아미도 -3- (트리 플루오 로메 톡시) 벤조 에이트 OCF 3 -migration (3A)를 통해 <ol><li> 50 ml의 압력 용기로 벤조 에이트 (9.05 밀리몰, 1.0 당량), 자기 볶음 바, 특산 2 (1.00 M)의 9.05 ml의 - 2.51 g의 메틸 4- ((트리 플루오 로메 톡시) 아세트 N)를 추가합니다. 스크류 캡으로 용기를 모자. </li><li> 20 시간 동안 안전 실드 뒤에 120 ℃에서 반응 혼합물을 교반한다. 주의 : 불순한 니트로 메탄폭발성이므로, 반응 혼합물 안전 실드 뒤에 교반한다. </li><li> RT 반응 액을 냉각. </li><li> 100㎖의 환저 플라스크에, 반응 혼합물을 전송. </li><li> 회전 증발기를 사용하여 진공 하에서 반응 혼합물을 농축시킨다. </li><li> 플래시 칼럼 크로마토 그래피는 헥산으로 용출하여 조질 생성물을 정제 : EtOAc로를 (9 : 1~7 : 3 (V / V)) (R의 F = 0.51 헥산 :을 EtOAc (4 : 1 (V / V))로 정제하여 메틸 -4- 아세트 아미도 -3- (트리 플루오 로메 톡시) 벤조산 2.13 g (7.69 밀리몰, 85 %). 주 :이 반응은 주변 대기 하에서 수행 될 수있다. 질소 분위기가 필요하지 않습니다. 물 응축기가 장착 된 둥근 바닥 플라스크를 대체 반응 장치로서 사용될 수있다. </li></ol> 신제품 4. 특성 <ol><li> 1 H, 13 C NMR 분광법 및 고해상도 질량 분광법으로 모든 신규 화합물을 특성화하고 19 F NMR 분광법을 사용불소 원자를 함유하는 화합물을 특성화. 34 </li></ol>

<ol>
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Rev. 96, 1757-1777 (1996).</li><li>Umemoto, T., Adachi, K., Ishihara, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CF3+oxonium+salts,+O-(trifluoromethyl)dibenzofuranium+salts:+in+situ+synthesis,+properties,+and+application+as+a+real+CF3++species+reagent.">CF3 oxonium salts, O-(trifluoromethyl)dibenzofuranium salts: in situ synthesis, properties, and application as a real CF3+ species reagent.</a> J. Org. Chem. 72, 6905-6917 (2007).</li><li>Stanek, K., Koller, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactivity+of+a+10-I-3+hypervalent+iodine+trifluoromethylation+reagent+with+phenols.">Reactivity of a 10-I-3 hypervalent iodine trifluoromethylation reagent with phenols.</a> J. Org. Chem. 73, 7678-7685 (2008).</li><li>Koller, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Zinc-mediated+formation+of+trifluoromethyl+ethers+from+alcohols+and+hypervalent+iodine+trifluoromethylation+reagents.">Zinc-mediated formation of trifluoromethyl ethers from alcohols and hypervalent iodine trifluoromethylation reagents.</a> Angew. Chem. Int. Ed. 48, 4332-4336 (2009).</li><li>Trainor, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+preparation+of+O-trifluoromethyl+carbohydrates.">The preparation of O-trifluoromethyl carbohydrates.</a> J. Carbohydr. Chem. 4, 545-563 (1985).</li><li>Nishida, M., Vij, A., Kirchmeier, R. L., Shreeve, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+polyfluoro+aromatic+ethers+-+a+facile+route+using+polyfluoroalkoxides+generated+from+carbonyl+and+trimethysilyl+compounds.">Synthesis of polyfluoro aromatic ethers - a facile route using polyfluoroalkoxides generated from carbonyl and trimethysilyl compounds.</a> Inorg. Chem. 34, 6085-6092 (1995).</li><li>Kolomeitsev, A. A., Vorobyev, M., Gillandt, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Versatile+application+of+trifluoromethyl+triflate.">Versatile application of trifluoromethyl triflate.</a> Tetrahedron Lett. 49, 449-454 (2008).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+deeper+insight+into+direct+trifluoromethoxylation+with+trifluoromethyl+triflate.">A deeper insight into direct trifluoromethoxylation with trifluoromethyl triflate.</a> J. Fluorine Chem. 131, 200-207 (2010).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+and+direct+trifluoromethoxylation+of+aliphatic+substrates+with+2,4-dinitro(trifluoromethoxy)benzene.">A new and direct trifluoromethoxylation of aliphatic substrates with 2,4-dinitro(trifluoromethoxy)benzene.</a> Adv. Synth. Catal. 352, 2831-2837 (2010).</li><li>Huang, C. H., Liang, T., Harada, S., Lee, E., Ritter, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Silver-mediated+trifluoromethoxylation+of+aryl+stannanes+and+arylboronic+acids.">Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.</a> J. Am. Chem. Soc. 133, 13308-13310 (2011).</li><li>Rozen, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+fluorinations+by+reagents+containing+the+OF+group.">Selective fluorinations by reagents containing the OF group.</a> Chem. Rev. 96, 1717-1736 (1996).</li><li>Venturini, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+trifluoro-methoxylation+of+aromatics+with+perfluoro-methyl-hypofluorite.">Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite.</a> J. Fluorine Chem. 140, 43-48 (2012).</li><li>Hojczyk, K. N., Feng, P., Zhan, C., Ngai, M. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethoxylation+of+arenes:+synthesis+of+ortho-trifluoromethoxylated+aniline+derivatives+by+OCF3+migration.">Trifluoromethoxylation of arenes: synthesis of ortho-trifluoromethoxylated aniline derivatives by OCF3 migration.</a> Angew. Chem. Int. Ed. 53, 14559-14563 (2014).</li><li>Still, W. C., Kahn, M., Mitra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+chromatographic+technique+for+preparative+separations+with+moderate+Resolution.">Rapid chromatographic technique for preparative separations with moderate Resolution.</a> J. Org. Chem. 43, 2923-2925 (1978).</li><li>Fiederling, N., Haller, J., Schramm, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Notification+about+the+Explosive+Properties+of+Togni's+Reagent+II+and+One+of+Its+Precursors.">Notification about the Explosive Properties of Togni's Reagent II and One of Its Precursors.</a> Org. Process Res. Dev. 17, 318-319 (2013).</li><li>Matousek, V., Pietrasiak, E., Schwenk, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+synthesis+of+hypervalent+iodine+reagents+for+electrophilic+trifluoromethylation.">One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.</a> J. Org. Chem. 78, 6763-6768 (2013).</li></ol>

The authors declare no competing financial interests.

인해 trifluoromethoxylated 아렌의 합성에 대해 일반적이고 사용자 친화적 인 절차의 부족, 많은 OCF 3 - 함유 방향족 화합물은 매우 고가이다. (34) 우리의 전략은 광범위한 관능기 허용 변위 각종 trifluoromethoxylated 아렌에 대한 쉬운 접근을 제공한다. 이들 화합물은 새로운 의약품, 농약, 및 재료의 발견과 개발을위한 가치있는 빌딩 블록을 제공 할 수있다. 히드라진 니트로 아렌의 로듐 - 촉매 환원을위한 수소 공급원으로 사용 하였다. 품질은 높은 수율의 감소 제품을 얻는 열쇠 중 하나입니다. 몇 개월 된 하이드라진을 사용했을 때 감소 수익률은 떨어졌다. 재현성을 보장하기 위해, 우리는 작은 20 ㎖ 유리 병에 대형 상업 병에서 히드라진의 일부를 옮겨 20 ㎖ 유리 병에서 사용. 또, 속도를 느리게하는 냉장고 (4 ℃)에 저장된분해. 또한, 히드라진의 느린 또한 좋은 수율로 깨끗한 히드 록실 아민을 얻기에 매우 중요하다. O- trifluoromethylation 라디칼은 중재 프로세스이기 때문에, 반응 혼합물로부터 산소의 배제가 중요하다. 용매 않은 탈기 클로로포름을 사용하거나 주위 분위기에서 반응이 낮은 수율 결과 수행. 우리의 예비 역학적 연구는 열 관련 OCF 3 -migration 프로세스가 nitrenium 이온과 trifluoromethoxide의 꽉 이온 쌍을 생성하기 위해 N-OCF 3 결합의 heterolytic 분열을 유도하는 것으로 나타났다. 34 Trifluoromethoxide는 오르 nitrenium 이온의 α 위치를 공격 한 다음 tautomerization는 오르토 원하는 trifluoromethoxylated 아닐린 유도체를 수득 하였다. 전자 불충분 한 기판에 nitrenium 이온의 형성은 정력적으로 선호되지이며, 따라서 더 높은 반응 온도를 필요로한다. 요약해서 말하면메리, 우리는 오르 -OCF 3 아닐린 유도체의 위치 선택적 합성을위한 일반 및 실험실 규모의 합성 프로토콜을보고했다. 이 전략은 몇 가지 독특한 특징 갖는다 : (ⅰ) 작용기 및 치환 패턴 허용되는 다양한; (ⅱ) 광범위한 합성 커뮤니티에 사용할 수 trifluoromethoxylation 렌더링 할 우리의 프로토콜의 동작 단순; 및 (iii) 최종 제품은 신규하며, 수명 및 재료 과학 연구를위한 유용한 합성 빌딩 블록으로서 사용될 수있다. 일부 해결 절차가 여기에 설명된다 : (i)가 냉동실에, 환원 생성물, 아릴 하이드 록실 아민을 보관하거나 즉시 다음 단계에 사용; (II) 니트로 아렌 또는 N- 히드 록시 아민의 보호의 감소를 통해 방지하기 위해 밀접하게 TLC와 감소 / 보호 반응을 모니터링; (III) 반응 혼합물로부터 산소를 배제 니트로 아렌과 O의 -trifluoromethylation의 저감에 중요하다; (ⅳ) 더 높은 reactioN 온도는 분자 내 OCF 3 -migration 단계에서 전자 결핍 아렌 필요합니다.

플루오 로메는 (OCF 3) 그룹이 때문에 높은 전기 음성도의 독특한 조합에 1935 년 2 트리 플루오로 에테르의 첫 번째 합성 이후의 삶과 재료 과학 연구에 지대한 영향을 만들었습니다 (χ = 3.7) 3과 우수한 친 유성 (Π X = 1.04), 4 플루오 로메 그룹은 의학, 농업, 및 재료 산업의 광범위한 응용 프로그램을 발견했다. 5-10 그러나, 유기 분자, 특히 방향족 화합물로 OCF 3 그룹의 손쉬운 도입은 합성 화학의 주요 과제로 남아. 지난 몇 년 동안이 문제를 해결하기 위해 노력 trifluoromethoxylated 아렌의 합성 변환의 소수의 개발을 주도 5-7,9-11 trichlorinated 전구체에 이러한 포함 (I) 염소 / 불소 교환,., 12 fluoroformates의 -17 (II) deoxyfluorination 18 </SUP&gt; (III) 산화 fluorodesulfurization; 19-21 (IV) 알코올의 친 전자 trifluoromethylation; 22-25 (V) 핵성 trifluoromethoxylation; 26-30, 아릴 스탄 난과 붕산염의 (VI), 전이 금속 - 매개 trifluoromethoxylation 31 및 (Ⅶ ) 라디칼 trifluoromethoxylation. 32,33 그러나 이러한 접근 방법 중 하나는 많은 열악한 기재 범위 고통 또는 높은 독성 및 / 또는 열적으로 불안정한 시약의 사용을 필요로한다. 따라서, OCF 3 인해 함유 화합물을 합성 일반 사용자 친화적 방법의 부족, OCF 3 그룹의 화학 전위는 충분히 악용되지 않았다. trifluoromethoxylation 반응에서 우리의 관심의 일환으로, 우리는 34 메틸 4- 아세트 아미도 -3- (트리 플루오 로메 톡시의 합성 본원 두 단계의 프로토콜 (예를 들어, 라디칼과 O의 -trifluoromethylation 열 유도 OCF 3 -migration)을 묘사메틸 4- (N의 -hydroxyacetamido) 벤조 에이트 (1A)에서 벤조 에이트 (3A)). 이 전략은 오르 -trifluoromethoxylated 아닐린 유도체의 넓은 범위의 합성에-작동하기 쉽고 적용 할 수있다.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">5% Rhodium on carbon</td>
			<td style="width:71px;">Aspira Scientific</td>
			<td style="width:119px;">300835</td>
			<td style="width:167px;">5% wt% dry loading</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">hydrazine monohydrate</td>
			<td style="width:71px;">Sigma-Alderich</td>
			<td style="width:119px;">13696HMV</td>
			<td style="width:167px;">Reagent grade, 98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Acetyl chloride</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">10176887</td>
			<td style="width:167px;">98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Sodium bicarbonate</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">134826</td>
			<td style="width:167px;">Chemical pure</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Cesium carbonate</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">12887</td>
			<td style="width:167px;">99.9%, metals basis</td>
		</tr>
		<tr height="148">
			<td height="148" style="height:148px;width:216px;">Togni Reagent II</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Prepared according to the literature procedure (ref 37). Caution: Pure Togni reagent II is impact and friction sensitive, treat it with great care (see ref. 36).</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Tetrahydrofuran</td>
			<td style="width:71px;">BDH</td>
			<td style="width:119px;">BDH1149-4LG</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Diethyl Ether</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">148221</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">Chloroform</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">141739</td>
			<td style="width:167px;">Dried over CaH2 and distilled</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">nitro methane</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">J03z053</td>
			<td style="width:167px;">Dried over CaSO4 and distilled</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Silica gel</td>
			<td style="width:71px;">SILICYCLE</td>
			<td style="width:119px;">60514</td>
			<td style="width:167px;">40-63 &#181;m (230-400 mesh)</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Cilite</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">2012040674</td>
			<td style="width:167px;">Not acid washed</td>
		</tr>
	</tbody>
</table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

플루오 로메 (OCF 3) 그룹을 함유 분자들은 약리학 및 생물 학적 속성을 원하는 보여줍니다. 그러나 trifluoromethoxylated 방향족 화합물의 손쉬운 합성은 유기 합성의 강력한 도전 남아있다. 종래의 접근 방식은 종종 열악한 기재 범위 고통, 또는 높은 독성 어려운 핸들의 사용을 필요로, 및 / 또는 열적으로 불안정한 시약. 여기서, 우리가 사용한 메틸 -4- 아세트 아미도 -3- (트리 플루오 로메 톡시) 벤조 에이트의 합성을위한 사용자 친화적 인 프로토콜을보고 -1- 플루오로 메틸 -1,2- benziodoxol -3- (1H) - 온 (시약 Togni II). 탄산 세슘의 촉매량의 존재하에 Togni 시약 II와 메틸 4- (N의 -hydroxyacetamido) 벤조 에이트 (1A)을 치료하는 CS (2 CO 3) RT에서 클로로포름 메틸 -4-을 수득 하였다 (N - (트리 플루오 로메 톡시) 아세트 아미도) 벤조산 (2A). 이 중간이어서 최종 제품 메틸 -4- 아세트 -3- (트라이 플루오로 전환시켰다120 ° C에서 니트로 메탄에 thoxy) 벤조 에이트 (3A). 이 절차는 일반적이며 새로운 의약품, 농약, 기능성 재료의 발견과 개발을위한 유용한 합성 빌딩 블록을 제공 할 수 -trifluoromethoxylated 오르토 아닐린 유도체의 광범위한 스펙트럼의 합성에 적용될 수있다.

메틸 4- (N의 -hydroxyacetamido) 벤조 에이트 (1A)는, 즉, 촉매로서 5 % Rh / C를 사용하여 히드라진 메틸 -4- 니트로 벤조 에이트를 환원하여 메틸 4- (형성한다 (두 단계 절차를 통해 92 % 격리 수율로 합성 하였다 N의 -hydroxyamino) 벤조 에이트, 생성 된 히드 록실 아민의 아세틸 보호 하였다). 탄산 세슘의 촉매량의 존재하에 Togni 시약 II와 1A의 O- Trifluoromethylation (CS를 RT에서 클로로포름 2 CO 3) 원하는 4-을 수득 하였다 ( N - 95 % 절연 수율 (트리 플루오 로메 톡시) 아세트) 벤조 에이트 (2A). 이 화합물은 열적 절연 85 % 수율로 목적하는 메틸 -4- 아세트 아미도 -3- (트리 플루오 로메 톡시) 벤조 에이트 (3A)을 수득하기 위해 120 ℃에서 2 특산 OCF 3 -migration 유도 받았다. 1 H, <sup&gt; 13 C, 및 최종 생성물 19 (3a)의 F NMR 스펙트럼을 각각도 1,도 2 및도 3에 도시된다. 13 C NMR 스펙트럼에 큰 결합 상수 (258.9 Hz에서)와 120.6 ppm으로 중주 피크를 구별는 CF 3 탄소에 해당합니다. OCF 3 -migration이 발생하는 경우, -65 PPM (2A)에서 19 F NMR의 급격한 변화는 (3A)이 관찰된다 -58.1ppm합니다. (3a)의 상세 특성화 데이터가 다음과 같이보고된다 : R의 F = 0.51 (헥산 / EtOAc로 4 : 1 (V / V)). NMR 분광학 : 1 H NMR (700 MHz의, CDCl3 중, 25 ° C, δ) : 8.56 (D, J = 8.6 Hz에서, 1H), 7.97 (D, J = 8.6 Hz에서, 1H), 7.93 (S, 1H) , 7.56 (. BR S, 1H), 3.92 (S, 3H), 2.27 (S, 3H) 13 C NMR (175 MHz의, CDCl3 중, δ 25 ° C). 168.5, 165.6, 137.2, 134.7, 129.3 , 125.8, 121.5, 120.8, 120.6 (Q, J = 258.9 Hz로), (52). 0.5, 25.2 (19) F NMR (376 MHz의, CDCl3 중, 25 ° C, δ) : -58.1 (들). 질량 스펙트럼 : HRMS (ESI-TOF) (m / z) : C 11 H 11 NO 3 4 F ([M + H] +)에 대한 계산치 278.0640는 278.0643를 발견했다. 이 프로토콜은 방향족 화합물 (표 1)의 다양한에 공통으로 적용 할 수있다. - (3리터 3G), CF 3 기 (3m, 3N) 반응 관능 에스테르를 비롯한 기 (3A, 3D)의 넓은 스펙트럼, 케톤 (3B), 니트릴 (3C), 에테르 (3E, 3m), 할로겐을 견뎌 아미드 (3O)과 헤테로 고리의 치환기 (3O). 할로겐 치환체, 특히 브롬과 나는 그들이 더 작용에 대한 합성 핸들을 제공하기 때문에 특히 유용하다. 파라 SELEC 이상 - 또한, 오르 높은 수준에서tivity는 (- 3리터 3 층, K) 관찰된다. 동일하지 않은 두 오르토 위치의 존재하에 regiocontrol의 낮은 수준 (3D, 3E, 3K, 3m)을 얻을 수있다. 또한, OCF 3 -migration 단계 반응 온도는 아렌의 전자적 성질에 의존한다. 일반적으로, 더 많은 전자 결핍 아렌 높은 반응 온도를 필요로한다. <img alt="그림 1" src="/files/ftp_upload/53789/53789fig1.jpg" /> (3a)의 1. 1 H NMR 스펙트럼을 그림. 화학 변화와 레이블이 특징적인 양자의 상대적 통합. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53789/53789fig1large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> (3a)의 2. 13 C NMR 스펙트럼을 그림. 특성 탄소의 화학 변화가 표시됩니다. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53789/53789fig2large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 3" src="/files/ftp_upload/53789/53789fig3.jpg" /> (3a)의 3. 19 F NMR 스펙트럼을 그림. 특성 불소의 화학 변화는 내부 기준으로 트리 플루오로 (-63.3 PPM)를 사용하여 레이블이 붙어 있습니다. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53789/53789fig3large.jpg" target="_blank">이 F의 더 큰 버전을 보려면 여기를 클릭하십시오</a>igure. <img alt="표 1" src="/files/ftp_upload/53789/53789table1highres.jpg" width="700" /> 표 아렌의 trifluoromethoxylation 1. 선정 예 반응 시간 :. 11-48 시간. 인용 수율과 이성체 비는 OCF 3 (2-3) -migration 단계 및 플래쉬 칼럼 크로마토 그래피에 의해 절연 재료이다. [A]의 50 ° C. [B]를 120 ° C. [C]의 140 ° C. [D] 5 % 미만의 파라 - 산물이 검출되었다. THF = 테트라 히드로 푸란; ACCL는 = 아세틸 클로라이드. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53789/53789table1highres.jpg" target="_blank">이 테이블의 더 큰 버전을 보려면 여기를 클릭하십시오.</a>

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

의 합성을위한 프로토콜<em&gt; 직교</em&gt; -trifluoromethoxylated 아닐린 파생 상품

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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9.8K 조회수.  State University of New York at Stony Brook. An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

비디오: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

생성 Cyanocarbenes의 응용 프로그램에 대한 고원자가 요오드 알키 트라이 플레이트의 합성

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

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Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

중간 과산화물을 통해 광화학 및 산 - 촉매 CH 기능화에 의한 항 바이러스 Tetrahydrocarbazole 유도체의 합성 (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

복잡한 아미노 구아니딘 함유 천연 제품의 합성에 대한 직접, 초기 단계 Guanidinylation 프로토콜

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST 바닐린-1의 합성에 대해 불균일 촉매로서

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

A Protocol for the Production of Gliadin-cyanoacrylate Nanoparticles for Hydrophilic Coating

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray coating. These nanoparticles are produced by the polymerization reaction of alkyl cyanoacrylate on the surface of cereal protein (gliadin) molecules. Alkyl cyanoacrylate is a monomer that instantly polymerizes at RT when it is applied to the surface of materials. Its polymerization reaction is initiated by the trace amounts of weakly basic or nucleophilic species on the surface, including moisture. Once polymerized, the polymerized alkyl cyanoacrylates show a strong affinity with the object materials because nitrile groups are in the backbone of poly (alkyl cyanoacrylate). Proteins also work as initiator for this polymerization because they contain amine groups that can initiate the polymerization of cyanoacrylate. If aggregated protein is used as an initiator, protein aggregate is surrounded by the hydrophobic poly(alkyl cyanoacrylate) chains after the polymerization reaction of alkyl cyanoacrylate. By controlling the experimental condition, particles in the nanometer range are produced. The produced nanoparticles readily adsorb to the surface of most materials including glass, metals, plastics, wood, leather, and fabrics. When the surface of a material is sprayed with the produced nanoparticle suspension and rinsed with water, the micellar structure of nanoparticle changes its conformation, and the hydrophilic proteins are exposed to the air. As a result, the nanoparticle-coated surface changes to hydrophilic.

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic. The produced nanoparticle is an assembly of gliadin-cyanoacrylate diblock copolymers. Spray coating with the produced nanoparticle changes the surface of target material to a hydrophilic surface.

친수성 코팅 글 리아 딘 - 시아 노 아크릴 레이트 나노 입자의 생산을위한 프로토콜

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Photoredox 촉매를 사용하여 가시 광선 중재 분산 중합에 의해 웜 형상 미셀 손쉬운 합성

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5&#39;-[CUA CGG AAU CAU]-3&#39; containing zero, one, or two modifications located at the C2&#39;-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2&#39;-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

This article provides a detailed procedure on the solid-phase synthesis, purification, and characterization of dodecamers of RNA modified at the C2&#39;-O-position. UV-vis and circular dichroism photometric analyses are used to quantify and characterize structural aspects, i.e., single-strands or double-strands.

2&#39;- 포스 핀 올리고 뉴클레오타이드를 함유하는 올리고머의 고상 합성을위한 프로토콜<em&gt; O</em&gt; 원형 이색 성을 통한 - 티오 페닐 메틸 변형 및 특성 분석

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

합성 및 올리고 peptoids의 질량 분석 분석

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges, since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for the simultaneous extraction of metabolites, proteins, and lipids (MPLEx) from the same soil sample was created by adapting a solvent-based approach. This MPLEx protocol has proven to be both simple and robust for many sample types, even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations.

A protocol is presented for simultaneously extracting metabolites, proteins, and lipids from a single soil sample, allowing reduced sample preparation times and enabling multi-omic mass spectrometry analyses of samples with limited quantities.

멀티-omic 토양 샘플의 분석을 위한 MPLEx 프로토콜

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and ...