- Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid
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Enantiomerically pure derivatives of 2-amino-4,4,4-trifluorobutanoic acid are in great demand as bioisostere of leucine moiety in the drug design. Here, we disclose a method specifically developedforlarge-scale(>150g)preparationofthetarget(S)-N-Fmoc-2-ami
- Han, Jianlin,Takeda, Ryosuke,Liu, Xinyi,Konno, Hiroyuki,Abe, Hidenori,Hiramatsu, Takahiro,Moriwaki, Hiroki,Soloshonok, Vadim A.
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supporting information
(2019/12/25)
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- TUBULYSIN ANALOGUES AS ANTICANCER AGENTS AND PAYLOADS FOR ANTIBODY-DRUG CONJUGATES AND METHODS OF TREATMENT THEREWITH
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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
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Page/Page column 153; 155; 158
(2019/06/17)
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- Expedient Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid via Alkylation of Chiral Nucleophilic Glycine Equivalent
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Here we disclose a practical asymmetric synthesis of an enantiomerically 97.8% ee pure N-Fmoc derivative of (S)-2-amino-4,4,4-trifluorobutanoic acid performed on >10 g scale of the target product. The method is based on alkylation (CF3-CH2-I) of a new generation of a chiral nucleophilic equivalent conducted at ambient temperature with an excellent stereochemical outcome. The developed protocol does not require any chromatographic separations and includes only one purification step via recrystallization of the final product.
- Mei, Haibo,Hiramatsu, Takahiro,Takeda, Ryosuke,Moriwaki, Hiroki,Abe, Hidenori,Han, Jianlin,Soloshonok, Vadim A.
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p. 629 - 634
(2019/04/30)
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- 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
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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.
- Nicolaou,Erande, Rohan D.,Yin, Jun,Vourloumis, Dionisios,Aujay, Monette,Sandoval, Joseph,Munneke, Stefan,Gavrilyuk, Julia
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supporting information
p. 3690 - 3711
(2018/03/21)
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- Helix propensity of highly fluorinated amino acids
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Highly fluorinated amino acids have been used to stabilize helical proteins for potential application in various protein-based biotechnologies. To gain further insight into the effect of these highly fluorinated amino acids on helix formation exclusively, we measured the helix propensity of three highly fluorinated amino acids: (S)-5,5,5,5′,5′,5′-hexafluoroleucine (Hfl), (S)-2-amino-4,4,4-trifluorobutyric acid (Atb), and (S)-pentafluorophenylalanine (Pff). We have developed a short chemoenzymatic synthesis of Hfl with extremely high enantioselectivity (>99%). To measure the helix propensity (w) of the amino acids, alanine-based peptides were synthesized, purified, and investigated by circular dichroism spectroscopy (CD). On the basis of the CD data, the helix propensity of hydrocarbon amino acids can decrease up to 24-fold (1.72 kcal·mol-1·residue-1) upon fluorination. This difference in helix propensity has previously been overlooked in estimating the magnitude of the fluoro-stabilization effect (which has been estimated to be 0.32-0.83 kcal·mol-1·residue-1 for Hfl), resulting in a gross underestimation. Therefore, the full potential of the fluoro-stabilization effect should provide even more stable proteins than the fluoro-stabilized proteins to date. Copyright
- Chiu, Hsien-Po,Suzuki, Yuta,Gullickson, Donald,Ahmad, Raheel,Kokona, Bashkim,Fairman, Robert,Cheng, Richard P.
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p. 15556 - 15557
(2007/10/03)
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