专利号:US-6376676-B1 优先权日:1993-06-30 标题 :Intermediates in the synthesis of (±)-camptothecin and related compounds and synthesis thereof 发明人:CURRAN DENNIS P; LIU HUI 权利人:UNIV PITTSBURGH 摘要:The present invention provides a short, convergent total synthesis of novel intermediates in the synthesis of (±)-camptothecin and related compounds. The present synthesis scheme includes a novel 4+1 radical annulation followed by another cyclization to simultaneously assemble rings B and C of the camptothecin compound. The present invention also provides novel chemical intermediates for such 4+1 radical annulations.
专利号:US-6252079-B1 优先权日:1993-06-30 标 题 :Intermediates in the synthesis of camptothecin and related compounds and synthesis thereof 发明人:CURRAN DENNIS P; BOM DAVID 权利人:UNIV PITTSBURGH 摘要:The present invention provides a short, convergent total synthesis of irinotecan and derivative compounds which comprises of a novel 4+1 radical annulation wherein the precursoris reacted with an aryl isonitrile having the formulawherein X is Br or I, and R4 is an alkyl group, an allyl group, a propargyl group or a benzyl group, and R16 is H, a C1-C6 alkoxy group, agroup wherein p is an integer between 4 and 12, or a C1-C12 acyclic dialkylamino group. The present invention also provides novel chemical intermediates for such 4+1 radical annulations.
专利号:US-2024269636-A1 优先权日:2021-06-14 标题:Ultra-high throughput on-chip synthesis of microgels with tunable mechanical properties 发明人:LEE DAEYEON; ISSADORE DAVID AARON; WU JINGYU; YADAVALI SAGAR PRASAD 权利人:UNIV PENNSYLVANIA 摘要:Hydrogel particles (microgels) generated using microfluidic methods have superb properties such as high size uniformity and precise control over degradation and release profiles, making them useful for applications in wound healing and injectable drug delivery. However, the throughput of microfluidics is constrained by the physics governing the flow of immiscible fluids confined within microchannels. This throughput tends to be several orders of magnitude lower than what would be necessary for commercial and clinical applications. Here, we demonstrate the scaling up of on-chip synthesis of microgels by parallelizing the microfluidic channels. Taking advantage of the established fabrication technologies developed by the semiconductor industry and a high flow control system, a 4-inch silicon microfluidic chip integrating more than 4,000 microfluidic devices is developed. By incorporating a high energy flood UV source, this chip allows the synthesis of poly (ethylene glycol) diacrylate microgel particles with diameter down to 30 m at a throughput above Ikg/hr. By using photomasks that enable milli-second scale control of the UV exposure, the stiffness of microgels can be varied.
专利号:US-2023287032-A1 优先权日:2020-08-14 标 题:Synthesis of fluorinated nucleotides 发明人:CHUNG CHEOL KEUN; LIU ZHIJIAN; MALIGRES PETER E; MAO EDNA; OBLIGACION JENNIFER V; PHILLIPS ERIC M; PIRNOT MICHAEL; POIRIER MARC; SONG ZHIGUO JAKE; WANG TAO 权利人:CHUNG CHEOL KEUN; LIU ZHIJIAN; MALIGRES PETER E; MAO EDNA; OBLIGACION JENNIFER V; PHILLIPS ERIC M; PIRNOT MICHAEL; POIRIER MARC; SONG ZHIGUO JAKE; WANG TAO; MERCK SHARP & DOHME LLC 摘要:The present invention relates to efficient processes useful in the preparation of fluorinated nucleosides, such as (O—{[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl}O,O-dihydrogen phosphorothioate, also known as 2′-(S)-fluoro-thio-adenosine monophosphate or 2′-F-thio-AMP. Such fluorinated nucleosides may be useful as a biologically active compound and or as an intermediate for the synthesis of more complex biologically active compounds. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.
专利号:US-6982333-B2 优先权日:1993-06-30 标 题:Intermediates in the synthesis of camptothecin and related compounds and synthesis thereof 发明人:CURRAN DENNIS P; JOSIEN HUBERT; KO SUNG BO 权利人:UNIV PITTSBURGH 摘要:The present invention provides a short, convergent total synthesis of camptothecin and related compounds which consists of a novel 4+1 radical annulation. The present invention also provides novel chemical intermediates for such 4+1 radical annulations.
专利号:US-8722886-B1 优先权日:2012-11-13 标题:Methods for the total chemical synthesis of enantiomerically-pure 7-(2′-trimethylsilyl)ethyl camptothecin 发明人:CHEN XINGHAI; HAUSHEER FREDERICK H; MALAKHOV ANDREY; KOCHAT HARRY 权利人:CHEN XINGHAI; HAUSHEER FREDERICK H; MALAKHOV ANDREY; KOCHAT HARRY; BIONUMERIK PHARMACEUTICALS INC 摘要:The present invention discloses and claims five (5) novel, highly efficient synthetic routes for the total synthesis of enantiomerically-pure (i.e., 99%) 7-(2′-trimethylsilyl)ethyl camptothecin (BNP1350; Karenitecin; Cositecan). These aforementioned synthetic schemes are the first to disclose the total syntheses of 7-(2′-trimethylsilyl)ethyl camptothecin using a highly novel direct, non-linear and convergent synthetic strategy which involves annealing the key C7-(trimethylsilyl)ethyl side chain-bearing A ring key synthons to an enantiomerically-pure tricyclic pyridone; rather than through the conventional methodology which incorporates the C7-(trimethylsilyl)ethyl side chain as the final synthetic step on a totally synthesized camptothecin parent compound. The current novel synthetic approaches reported herein since utilize desirably functionalized A-ring with preinstalled trimethyl silyl ethyl side chain, the aforementioned synthetic methodologies have a wider scope of making wide range of pharmaceutically relevant A-ring substituted BNP1350 analogs by substituting desirably functionalized nitro or protected amino phenyl carboxy A-ring as the starting material.
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