180715-99-5Relevant articles and documents
The dolastatins; 18: Stereospecific synthesis of dolaproine
Pettit, George R.,Burkett, Douglas D.,Barkóczy, József,Breneman, Gary L.,Pettit, William E.
, p. 719 - 725 (1996)
Dolastatin 10 (1), isolated from the sea hare Dolabella auricularia, has proved to be an exceptionally promising antineoplastic substance. Synthesis of this new and important peptide has been achieved. However, a more convenient and stereoselective synthesis of its three chiral center dolaproine (2a) unit has become necessary. A practical solution to this challenging problem was realized by employment of the following key reaction steps. Chiral oxazolidinone 5 was condensed at -75°C with S-prolinal 4 using dibutylboron triflate to direct the stereochemical course of the aldol reaction. Methylation of the product (6, 60-80% yields) and cleavage of the amide, in 83 and 93% yields respectively, completed a facile route to N-Boc-dolaproine (2b). Pertinent aspects of the aldol reaction and cleavage of oxazolidinone amides are discussed.
NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG
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Paragraph 0241-0242, (2021/05/14)
PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
CONJUGATION OF A CYTOTOXIC DRUG WITH BIS-LINKAGE
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Paragraph 0695-0697, (2020/01/08)
What provided is the conjugation of cytotoxic to a cell-binding molecule with a bis-linker(dual-linker) as shown in Formula (I). It provides bis-linkage methods of making a conjugate of a cytotoxic drug molecule to a cell-binding agent in a specific manner. It also relates to application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.