79677-62-6Relevant academic research and scientific papers
RA-XXV and RA-XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation
Hitotsuyanagi, Yukio,Hirai, Masahito,Odagiri, Masumi,Komine, Miho,Hasuda, Tomoyo,Fukaya, Haruhiko,Takeya, Koichi
, p. 205 - 215 (2019)
Two RA-series bicyclic hexapeptides, RA-XXV (4) and RA-XXVI (5), which have no N-methyl group at Tyr-5, were isolated from the roots of Rubia cordifolia L. Their amino acid compositions and sequences were determined by interpretation of MS, and 1D and 2D NMR data and their relative structures were elucidated by XRD analysis of 4 and RA-XXVI acetate (6). The absolute stereochemistry of 4 was established by the total synthesis of 4, and that of 5, by the chemical correlation with 4. Peptides 4 and 5 exhibited cytotoxicity toward human promyelocytic leukemia HL-60 (IC50=0.062 and 0.066 μm, respectively) and human colonic carcinoma HCT-116 (IC50=0.028 and 0.051 μm, respectively) cell lines. Analysis of the conformational structures of 4 and 6 in the crystalline state and those of 4 and 5 in solution revealed that the N-methyl group at Tyr-5 functions to make this series of peptides preferentially adopt the active conformation.
Synthesis of the Rubiyunnanin B Core Aglycon
Moschitto, Matthew J.,Lewis, Chad A.
, p. 4773 - 4777 (2016/10/13)
Rubiyunnanin B possesses an intriguing anticancer profile whose activity is dependent on the glycosylation of a fused tyrosinyl residue. We have developed a rapid synthesis of the rubiyunnanin B dityrosine core using a Suzuki coupling. Furthermore, the atropisomeric and isomeric products obtained were identified and their distribution controlled. The two major products obtained from the dityrosine coupling were discovered to be locked cis/trans isomers of the internal amide with atropisomerization quantifiable on the NMR timescale.
LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs
Augustyn, Evan,Finke, Karissa,Zur, Arik A.,Hansen, Logan,Heeren, Nathan,Chien, Huan-Chieh,Lin, Lawrence,Giacomini, Kathleen M.,Colas, Claire,Schlessinger, Avner,Thomas, Allen A.
supporting information, p. 2616 - 2621 (2016/05/09)
The transporter protein Large-neutral Amino Acid Transporter 1 (LAT-1, SLC7A5) is responsible for transporting amino acids such as tyrosine and phenylalanine as well as thyroid hormones, and it has been exploited as a drug delivery mechanism. Recently its role in cancer has become increasingly appreciated, as it has been found to be up-regulated in many different tumor types, and its expression levels have been correlated with prognosis. Substitution at the meta position of aromatic amino acids has been reported to increase affinity for LAT-1; however, the SAR for this position has not previously been explored. Guided by newly refined computational models of the binding site, we hypothesized that groups capable of filling a hydrophobic pocket would increase binding to LAT-1, resulting in improved substrates relative to parent amino acid. Tyrosine and phenylalanine analogs substituted at the meta position with halogens, alkyl and aryl groups were synthesized and tested in cis-inhibition and trans-stimulation cell assays to determine activity. Contrary to our initial hypothesis we found that lipophilicity was correlated with diminished substrate activity and increased inhibition of the transporter. The synthesis and SAR of meta-substituted phenylalanine and tyrosine analogs is described.
Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement
David, Nadège,Pasceri, Raffaele,Kitson, Russell R. A.,Pradal, Alexandre,Moody, Christopher J.
supporting information, p. 10867 - 10876 (2016/07/27)
A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A.
The diazo route to diazonamide A: Studies on the tyrosine-derived fragment
Palmer, Francine N.,Lach, Franck,Poriel, Cyril,Pepper, Adrian G.,Bagley, Mark C.,Slawin, Alexandra M. Z.,Moody, Christopher J.
, p. 3805 - 3811 (2007/10/03)
Various approaches to the tyrosine-derived fragment of the marine secondary metabolite diazonamide A are described. Initial efforts were focused on the originally proposed structure of the natural product, and a feasibility study established that a model
Synthesis of the side chain cross-linked tyrosine oligomers dityrosine, trityrosine, and pulcherosine
Skaff, Ojia,Jolliffe, Katrina A.,Hutton, Craig A.
, p. 7353 - 7363 (2007/10/03)
An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation-Suzuki coupling to give protected dityrosine. The choice of
A convenient preparation of dityrosine via Miyaura borylation-Suzuki coupling of iodotyrosine derivatives
Hutton, Craig A.,Skaff, Ojia
, p. 4895 - 4898 (2007/10/03)
Dityrosine has been prepared from 3-iodo-L-tyrosine derivatives by sequential Miyaura borylation and Suzuki coupling reactions. A tandem borylation-coupling protocol results in improved yields of the dityrosine derivatives. Suitable protecting group strat
Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides
Burke Jr., Terrence R.,Yao, Zhu-Jun,Zhao, He,Milne, George W. A.,Wu, Li,Zhang, Zhong-Yin,Voigt, Johannes H.
, p. 9981 - 9994 (2007/10/03)
Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus- containing phosphotyrosyl (pTyr) mimetics, wh
