133565-37-4Relevant academic research and scientific papers
Process Development and GMP Production of a Conjugate Warhead: Auristatin F-HPA-Ala/TFA (XMT-1864/TFA)
Conlon, Patrick R.,Gurijala, Venu Reddy,Kaufman, Michael,Li, Dachang,Li, Jiuyuan,Li, Yuanyuan,Reddy, Bollu Satyanarayan,Wagler, Thomas,Wang, Zedong,Xu, Zhongmin,Yin, Mao,Yurkovetskiy, Aleksandr V.,Zhu, Lei
, (2022/03/01)
An efficient, large-scale manufacturing process is described for XMT-1864/TFA (1-TFA), an auristatin F derivative, used as a novel, highly potent, cytotoxic warhead in Mersana's oncology antibody-drug conjugate platforms. The process achieves high diastereomeric purity and controls the impurities with all intermediates readily isolated by crystallization or precipitation in high yield and purity. Protecting groups were selected to ensure tolerability, scalability, and stability of the intermediates under various solution-phase peptide coupling conditions. Crystallization of the final product was developed to remove specified impurities and provide a high-purity active warhead molecule for use in the bioconjugation processing. The convergent synthesis involving six non-GMP steps and five GMP steps has been carried out in multiple cGMP productions on 1-kg scale to produce 1-TFA in >98% chemical purity and 1% total diastereomeric contamination with ～50% overall yield for the GMP steps.
Stereoselective Synthesis of Dolastatin 10 and Its Congeners
Shioiri, Takayuki,Hayashi, Kyoko,Hamada, Yasumasa
, p. 1913 - 1924 (2007/10/02)
Efficient synthesis of dolastatin 10 (1), a potent antitumor peptide from a sea hare Dolabella auricularia, has been achieved in a stereoselective manner.Trisnordolastatin 10 (2) and its C9-epimer (3) have also been synthesized.
On the reversal of the stereoselectivity in the Evans aldol reaction of α-amino aldehydes
Hayashi,Hamada,Shioiri
, p. 7287 - 7290 (2007/10/02)
Reversal of the stereoselectivity in the Evans aldol reaction of Boc-(S)-prolinal (3), observed during the total synthesis of dolastatin 10 (1), was proved to be due to the amounts of dibutylboron triflate and triethylamine. (R)-Alaninal derivatives (14)
Efficient stereoselective synthesis of dolastatin 10, an antineoplastic peptide from a sea hare
Hamada, Yasumasa,Hayashi, Kyoko,Shioiri, Takayuki
, p. 931 - 934 (2007/10/02)
The stereoselective and efficient synthetic route to dolastatin 10, an antineoplastic peptide from a sea hare, has been developed. Dolaproine, one of the unusual constituents, was prepared in a highly stereoselective manner by the Evans aldol methodology.
