773155-73-0Relevant academic research and scientific papers
Stereoselective access to tubuphenylalanine and tubuvaline: Improved Mn-mediated radical additions and assembly of a tubulysin tetrapeptide analog
Friestad, Gregory K.,Banerjee, Koushik,Marié, Jean-Charles,Mali, Umesh,Yao, Lei
, p. 294 - 298 (2016)
Synthesis of tubuphenylalanine and tubuvaline (Tuv), substituted γ-amino acid building blocks for tubulysin family of antimitotic compounds, has been improved using a radical addition reaction in the presence of unprotected hydroxyl functionality. The key carbon-carbon bond construction entails stereoselective Mn-mediated photolytic additions of alkyl iodides to the C=N bond of chiral N-acylhydrazones, and generates the chiral amines in high yield with complete stereocontrol. Reductive N-N bond cleavage and alcohol oxidation converted these amino alcohols into the corresponding γ-amino acids. The route to Tuv proceeded via peptide coupling with serine methyl ester, followed by a high-yielding sequence to convert the serine amide to a thiazole. Finally, peptide bond construction established the tubulysin framework in the form of a C-terminal alcohol analog. Attempted oxidation to the C-terminal carboxylate was unsuccessful; control experiments with dipeptide 18 showed a cyclization interfered with the desired oxidation process.
Diastereocontrol in Radical Addition to β-Benzyloxy Hydrazones: Revised Approach to Tubuvaline and Synthesis of O-Benzyltubulysin v Benzyl Ester
Li, Manshu,Banerjee, Koushik,Friestad, Gregory K.
, p. 15139 - 15152 (2021/11/01)
Radical addition to chiral N-acylhydrazones has generated unusual amino acids tubuphenylalanine (Tup) and tubuvaline (Tuv) that are structural components of the tubulysin family of picomolar antimitotic agents and previously led to a tubulysin tetrapeptide analog with a C-terminal alcohol. To improve efficiency in this synthetic route to tubulysins, and to address difficulties in oxidation of the C-terminal alcohol, here we present two alternative routes to Tuv that (a) improve step economy, (b) provide modified conditions for Mn-mediated radical addition in the presence of aromatic heterocycles, and (c) expose an example of double diastereocontrol in radical addition to a β-benzyloxyhydrazone with broader implications for asymmetric amine synthesis via radical addition. An efficient coupling sequence affords 11-O-benzyltubulysin V benzyl ester.
Stereoselective Mn-mediated coupling of functionalized iodides and hydrazones: A synthetic entry to the tubulysin γ-amino acids
Friestad, Gregory K.,Marie, Jean-Charles,Deveau, Amy M.
, p. 3249 - 3252 (2007/10/03)
(Chemical Equation Presented) Synthesis of γ-amino acids, important building blocks in bioorganic and natural product chemistry, is accomplished using a stereoselective carbon-carbon bond construction of the chiral amine. Alkyl iodides and chiral hydrazon
