856838-98-7Relevant articles and documents
TUBULYSIN ANALOGUES AS ANTICANCER AGENTS AND PAYLOADS FOR ANTIBODY-DRUG CONJUGATES AND METHODS OF TREATMENT THEREWITH
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Page/Page column 112-113, (2019/06/17)
In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect
Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates
Nicolaou,Erande, Rohan D.,Yin, Jun,Vourloumis, Dionisios,Aujay, Monette,Sandoval, Joseph,Munneke, Stefan,Gavrilyuk, Julia
supporting information, p. 3690 - 3711 (2018/03/21)
Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described.
Preparation method of levobupivacaine hydrochloride
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Paragraph 0043; 0045-0047, (2017/09/26)
The invention belongs to the technical field of chemical synthesis and particularly relates to a preparation method of levobupivacaine hydrochloride. The preparation method comprises the steps of carrying out catalytic hydrogenation on racemic or S-form 2-piperidinecarboxylicacid as a raw material and n-butanal so as to obtain 1-butylpiperidine-2-carboxylic acid, carrying out condensation reaction on 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline so as to generate bupivacaine or levobupivacaine, and carrying out subsequent treatment, so as to obtain a final product, namely levobupivacaine hydrochloride. Compared with existing synthetic routes, the preparation method has the advantages that the synthetic route is short, the method is simple, convenient in operation, low in cost and easy for industrial production, reaction conditions of each step are relatively mild, the process is stable, a strong-corrosion chlorinated reagent is not used, and the environmental pollution is reduced.
Preparation method of levobupivacaine hydrochloride
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Paragraph 0044; 0045; 0046; 0047, (2017/07/19)
The invention belongs to the technical field of chemical synthesis and in particular relates to a preparation method of levobupivacaine hydrochloride. The preparation method takes racemic or S-configuration 2-piperidinecarboxylic acid as a starting raw material and comprises the following steps: taking the starting raw material and n-butylaldehyde to react and carrying out borohydride reduction reaction to obtain 1-butylpiperidine-2-carboxylic acid; taking the 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline to be subjected to condensation reaction, so as to generate bupivacaine or levobupivacaine; carrying out subsequent treatment to obtain a final product levobupivacaine hydrochloride. Compared with an existing synthesis route, the preparation method has the advantages of short synthesis route, simple method, convenience for operation, low cost and easiness for industrial production; reaction conditions of each step are relatively moderate, a process is stable, a strong-corrosion chlorination reagent is not used, the pollution to environment is reduced and the like.
DESACETOXYTUBULYSIN H AND ANALOGS THEREOF
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Page/Page column 162, (2016/09/22)
In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein R1, R2, R3, R4, X1, X2, X3, and A1 are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein.