244033-72-5

Upstream product

• 3699-66-9 ethyl 2-diethoxyphosphorylpropionate 
• 72155-45-4 Boc-L-phenylalaninal 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 4522-04-7 ethyl N-{[(1,1-dimethylethyl)oxy]carbonyl}-L-phenylalaninate 
• 21382-82-1 (carbethoxyethylidene)triphenylphosphorane 
• 30018-16-7 (1-ethoxycarbonylethyl)triphenylphosphonium bromide 
• 51987-73-6 (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester 
• 66605-57-0 (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 3182-95-4 L-Phenylalaninol 

Downstream Products

• 1219930-75-2 methyl (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoate 
• 1174764-13-6 (2S,4R)-4-[((R)-2-{3-[methyl-(N-methyl-(R)-pipecolyl-(S)-isoleucyl)-amino]-4-methyl-pentyl}-thiazole-4-carbonyl)-amino]-2-methyl-5-phenyl-pentanoic acid trifluoroacetic acid salt 
• 1207472-51-2 ethyl (4R)-4-[(tert-butoxycarbonyl)amino]-2-methyl-5-phenylpentanoate 
• 1266130-89-5 (S)-(E)-tert-butyl (5-hydroxy-4-methyl-1-phenylpent-3-en-2-yl)carbamate 
• 1207472-52-3 (R)-N-(tert-butoxycarbonyl)-4-methyl-1-phenylpentan-2-amine 
• 1207472-58-9 methyl (2S,4R)-4-[((R)-2-{3-[(N-benzyloxycarbonyl-(R)-pipecolyl-(S)-isoleucyl)methylamino]-4-methylpentyl}thiazole-4-carbonyl)amino]-2-methyl-5-phenylpentanoate 

Relevant academic research and scientific papers

Design, Synthesis, and Cytotoxic Activity of New Tubulysin Analogues

Synthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic

Total synthesis of tubulysin U and N14-desacetoxytubulysin H

A concise and efficient procedure for the total synthesis of tubulysin U and N14-desacetoxytubulysin H has been developed with high stereoselectivity on a gram scale. This synthesis features an elegant cascade one-pot process to install the challenging th

CONJUGATE OF CELL-BINDING RECEPTOR WITH CYTOTOXIC AGENT

PROBLEM TO BE SOLVED: To provide a conjugate of a potent cytotoxic agent with a cell-surface receptor binding molecule for targeted treatment. SOLUTION: According to the present invention, there is provided a conjugate having a structure of formula (I) and a pharmaceutical acceptable salt and a solvate thereof. The conjugate is used for treating cancer, autoimmune disease, and infectious disease. (T is a targeting or binding ligand; L is a releasable linker; a broken line is a linkage bond that L connects to a molecule inside the bracket independently; n is an integer of 1 to 20; m is an integer of 1 to 10; and a structure in parentheses is a potent antimitotic agent/drug.) SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

Total Synthesis and Biological Evaluation of Tubulysin Analogues

We report a second-generation synthesis of the exceedingly potent antimitotic agent N14-desacetoxytubulysin H (1) as well as the preparation of nine analogues of this lead structure. Highlights of our synthetic efforts include an efficient late

Synthesis and biological evaluation of pretubulysin and derivatives

Pretubulysin, a biosynthetic precursor of the tubulysins, shows potent biological activity in the subnanomolar range towards various tumor cell lines. Its activity is only slightly less than those of the structurally more complex tubulysins. With a straig

Synthesis of the tubuvaline-tubuphenylalanine (Tuv-Tup) fragment of tubulysin

(Chemical Equation Presented) Advanced intermediates and analogues of tubulysins were prepared in a convergent strategy.

Diels-Alder Reactions of Amino Acid-Derived Trienes

Triene precursors (1a-e, 2a-k) were constructed for substrate-controlled asymmetric Diels-Alder reactions. Boc-L-phenylalanal and Boc-L-valinal were condensed with triethyl phosphonoacetate or 2-phosphonopropionate to generate the α,β-unsaturated esters as dienophiles. Removal of the Boc group to give free amines 4a-d, which after, or without N-benzylation, were treated with 3,5-hexadienoyl chloride to give 1a-e, or with 2,4-hexadienoyl chloride to afford 2a-f. The trienes 2g-i were prepared via reductive alkylation of amines 4a-i with 2,4-hexadienal. The secondary amide triene 1a failed to yield any Diels-Alder product when heated at 170°C. The tertiary amide trienes 1b-e produced in refluxing toluene the major cycloaddition products that were cis-fused and derived from the exo transition states. Trienes 2a-k underwent surprisingly facile Diels-Alder reactions to produce the major trans-fused isomers that were derived from the endo transition states. For trienes 2b-h and 2j,k, Diels-Alder reactions proceeded at room temperature. For the primary amide 2a, the Diels-Alder reaction proceeded smoothly in refluxing toluene. The tertiary amide triene 22 was constructed to have two electron-withdrawing ester substituents at the termini of the triene. The Diels-Alder reaction of 22 took place spontaneously at room temperature upon benzoylation of the secondary amine 21 and produced a single isomer derived from the endo transition state. 1,3-Allylic strain is discussed as an important factor in control of the diastereo-selectivity.