专利号:US-5220016-A 优先权日:1991-07-29 标 题:Synthesis of navelbine analogs 发明人:MAGNUS PHILIP D; THURSTON LEE S 权利人:UNIV TEXAS 摘要:The invention is a de novo synthesis of the norcatharanthine moiety of navelbine. The synthesis includes condensing a Grignard reagent prepared from an amine-protected R(+)-piperidinyl methanol with an N-protected 2-methoxyoxalyl indole. The indole N-protecting group is removed to provide a 2-methoxyindole hydroxy ester which is coupled to vindoline. After removal of the amineprotecting group from the piperidinyl group, ring closure to the indole moiety provides dihydrodesethyl navelbine. Other derivatives and analogs of navelbine with potential clinical applications in cancer chemotherapy may be readily synthesized. The synthesis opens a route to a wide variety of navelbine modifications, including modifications at or near the tryptamine bridge.
专利号:US-2015182634-A1 优先权日:2012-12-28 标 题:Molecular Design and Chemical Synthesis of Pharmaceutical-Ligands and Pharmaceutical-Pharmaceutical Analogs with Multiple Mechanisms of Action 发明人:COYNE CODY P; BEAR RYAN; JONES TONI 权利人:COYNE CODY P; BEAR RYAN; JONES TONI 摘要:Multi-phase and single-phase chemical reaction schemes have been developed for the synthesis of pharmaceutical-ligand analogs, pharmaceutical-pharmaceutical analogs, and similar molecular-molecular analogs that possess multiple mechanisms of action. The multi-phase organic chemical reaction schemes include relatively mild reaction conditions, high end product yields, and comparatively rapid completion of chemical reactions, which are all of particular utility for the synthesis of preparations including covalent pharmaceutical-receptor ligand or pharmaceutical-immunoglobulin analogs. Examples of pharmaceutical-ligand preparations that can be synthesized utilizing the multi-step chemical reaction schemes include covalent chemotherapeutic-ligand agents that possess selective targeted delivery properties and a capacity to exert additive and synergistic levels of cytotoxic anti-neoplastic potency. Pharmaceutical-pharmaceutical analogs, including chemotherapeutic-chemotherapeutic analogs that are capable of exerting multiple mechanisms of action, can be synthesized using either of the described multi-phase or single-phase organic chemistry reaction schemes. Each of these representative examples has utility against a spectrum of disease states including, for example, neoplastic conditions such as mammary adenocarcinoma/carcinoma, ovarian carcinoma, prostatic carcinoma, intestinal carcinoma, melanoma, leukemia, myeloma, and lymphoma.
专利号:US-4841045-A 优先权日:1985-03-12 标 题 :Synthesis of vinblastine and vincristine type compounds 发明人:KUEHNE MARTIN 权利人:UNIV VERMONT 摘要:A new process for the stereospecific synthesis of alkaloids of the vinblastine and vincristine type including the synthesis of vinblastine and vincristine as well novel alkaloids which are active as anti-tumor agents.
专利号:US-4897477-A 优先权日:1985-03-12 标题:Synthesis of vinblastine and vincristine type compounds 发明人:KUEHNE MARTIN 权利人:UNIV VERMONT 摘要:A new process for the stereospecific synthesis of alkaloids of the vinblastine and vincristine type including the synthesis of vinblastine and vincristine as well novel alkaloids which are active as anti-tumor agents.
专利号:US-RE37449-E 优先权日:1987-02-06 标题:Process of synthesis of 3′,4′-anhydrovinblastine, vinblastine and vincristine 发明人:KUTNEY JAMES P; CHOI LEWIS S L; NAKANO JUN; TSUKAMOTO HIROKI; BOULET CAMILLE A; MCHUGH MICHAEL 权利人:UNIV BRITISH COLUMBIA 摘要:The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.
专利号:US-10973847-B2 优先权日:2017-06-30 标题 :Core-to-surface polymerization for the synthesis of star polymers and uses thereof 发明人:JOHNSON JEREMIAH A; GOLDER MATTHEW R 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:Disclosed are methods, compositions, reagents, systems, and kits to prepare star polymers, as well as compositions and uses thereof. Various embodiments show that synthesis of these polymers contain low metal concentration to provide polymers for diverse biomedical applications including in vivo applications.