- Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides
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An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
- van der Heijden, Gydo,van Schaik, Timo B.,Mouarrawis, Valentinos,de Wit, Martin J. M.,Velde, Christophe M. L. Vande,Ruijter, Eelco,Orru, Romano V. A.
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supporting information
p. 5313 - 5325
(2019/06/10)
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- USE OF 21 (S) ARGATROBAN FOR TREATING THROMBOSIS AND INHIBITING PLATELET AGGREGATION
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This invention refers to the preparation of a direct thrombin inhibitor, especially the application of a thrombin inhibitor of 21 (s) Argatroban. The chemical name of 21(S) Argatroban is: (2R, 4R) -1- { (2S) -5- [ ( Aminoiminomethyl) amino] -1-oxo-2-{ [ (3S) -1, 2, 3, 4-tetrahydro-3-methyl-8- quinolinyl] sulf onyl] amino] pentyl] -4-methyl-2-piperidine carboxylic acid, and the supplies which can be accepted in medicine. The 21(S) prolongation of coagulation time of whole blood (CT) is twice as long as 21 (R) 's, prolongation of recalcif ication time (RT) is three times of 21 (R) 's, extending prothrombin time (PT) is twice as 21 (R) 's, prolongation of thrombin time (TT) is little stronger than 21 (R) and prolongation of kaolin partial thromboplastin time (APTT) is twice as 21(R). Anticoagulation action of 21(S) Argatroban is 2-3 times of 21(R). Therefore, the 21 (S) isomer of Argatroban can be used as a new generation of direct thrombin inhibitor.
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Page/Page column 5-6
(2008/12/08)
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