专利号:US-5877278-A 优先权日:1992-09-24 标题:Synthesis of N-substituted oligomers 发明人:ZUCKERMANN RONALD N; GOFF DANE A; NG SIMON; SPEAR KERRY; SCOTT BARBARA O; SIGMUND AARON C; GOLDSMITH RICHARD A; MARLOWE CHARLES K; PEI YAZHONG; RICHTER LUTZ; SIMON REYNA 权利人:CHIRON CORP 摘要:A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two 'sub-monomers' directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by -NH2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a solid support-bound alpha -haloacetamide) with a sufficient amount of a second sub-monomer comprising an -NH2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology of the present method makes these oligomers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of the invention, such as N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of peptide-like compounds not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability. Combinatorial libraries of cyclic compounds are disclosed wherein the cyclic compounds are comprised of at least one ring structure derived from cyclization of a peptoid backbone. The diversity of product compounds is generated by the sequential addition of substituted submonomers. The combinatorial library includes 10 or more, preferably 100 or more, and more preferably 1,000 or more distinct and different compounds. The library includes each of the product compounds in retrievable and analyzable amounts and preferably includes at least one biologically active compound. Methods of synthesizing the combinatorial libraries and assay devices produced using the libraries are disclosed as is methodology for screening for and obtaining biologically active cyclic organic compounds.
专利号:EP-0443532-B1 优先权日:1990-02-20 标题:Temporary minimal protection synthesis of LH-RH analogs 发明人:NESTOR JOHN J JR; MCCLURE NATALIE L 权利人:SYNTEX INC 摘要:A solid phase synthesis of LH-RH analogs in which the amino acids serine and histidine, if present, are side chain protected during the synthesis with groups labile to selected alpha -amino or deprotecting agents.
专利号:US-10266503-B1 优先权日:2016-05-24 标 题 :Sulfoxide ligand metal catalyzed oxidation of olefins 发明人:WHITE M CHRISTINA; AMMANN STEPHEN E; LIU WEI; MA RULIN 权利人:UNIV ILLINOIS 摘要:The enantioselective synthesis of isochroman motifs has been accomplished via Pd(II)-catalyzed allylic C—H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C—H oxidation reaction proceeds with the broadest scope and highest levels asymmetric induction reported to date (avg. 92% ee, 13 examples ≥90% ee). Additionally, C(sp 3 )-N fragment coupling reaction between abundant terminal olefins and N-triflyl protected aliphatic and aromatic amines via Pd(II)/sulfoxide (SOX) catalyzed intermolecular allylic C—H amination is disclosed. A range of 52 allylic amines are furnished in good yields (avg. 76%) and excellent regio- and stereoselectivity (avg. >20:1 linear:branched, >20:1 E:Z). For the first time, a variety of singly activated aromatic and aliphatic nitrogen nucleophiles, including ones with stereochemical elements, can be used in fragment coupling stiochiometries for intermolecular C—H amination reactions.
专利号:WO-8911473-A1 优先权日:1988-05-27 标 题:Process for the synthesis of o-substituted oxime compounds 发明人:CHEMPOLIL THOMAS MATHEW 权利人:ALLIED SIGNAL INC 摘要:A novel process for the production of O-substituted oximes is disclosed. The process involves reacting an oxime with an alkali-metal hydroxide optionally in a solvent which forms an azeotrope with water to form a mixture of the alkali metal salt of the oxime and water, removing all or a portion of the water by distilling the mixture azeotropically and reacting the distilled mixture with an alpha halo carboxylic acid.
专利号:US-6774125-B2 优先权日:1998-06-22 标 题:Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds 发明人:AUDIA JAMES E; THOMPSON RICHARD C; WILKIE STEPHEN C; BRITTON THOMAS C; PORTER WARREN J; HUFFMAN GEORGE W; LATIMER LEE H 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
专利号:US-6509331-B1 优先权日:1998-06-22 标题:Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds 发明人:AUDIA JAMES E; THOMPSON RICHARD C; WILKIE STEPHEN C; BRITTON THOMAS C; PORTER WARREN J; HUFFMAN GEORGE W; LATIMER LEE H 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit beta-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits beta-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
参考标题:An Approach To Spirooxindoles Via Palladium-Catalyzed Remote C-H Activation And Dual Alkylation With Ch2Br2 作者:Changdong Shao,Zhuo Wu,Xiaoming Ji,Bo Zhou,Yanghui Zhang 摘要:A Facile And Efficient Approach For The Synthesis Of Spirooxindoles Has Been Developed Via The Coupling Of Spirocyclic C, C-Palladacycles With Ch2Br2. The Key Spirocyclic Palladacycles Are Generated Catalytically Via Intramolecular Remote C-H Activation. A Range Of Spirooxindoles Can Be Synthesized In Good To Excellent Yields From Readily Available Starting Materials.
合成参考文献
摘要:Kwiecień, H., Science of Synthesis Knowledge Updates, (2014) 4, 165.