599201-28-2Relevant articles and documents
Total Synthesis and Antimycobacterial Activity of Ohmyungsamycin A, Deoxyecumicin, and Ecumicin
Hawkins, Paige M. E.,Tran, Wendy,Nagalingam, Gayathri,Cheung, Chen-Yi,Giltrap, Andrew M.,Cook, Gregory M.,Britton, Warwick J.,Payne, Richard J.
, p. 15200 - 15205 (2020/10/23)
The ohmyungsamycin and ecumicin natural product families are structurally related cyclic depsipeptides that display potent antimycobacterial activity. Herein the total syntheses of ohmyungsamycin A, deoxyecumicin, and ecumicin are reported, together with the direct biological comparison of members of these natural product families against Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB). The synthesis of each of the natural products employed a solid-phase strategy to assemble the linear peptide precursor, involving a key on-resin esterification and an optional on-resin dimethylation step, before a final solution-phase macrolactamization between the non-proteinogenic N-methyl-4-methoxy-l-tryptophan amino acid and a bulky N-methyl-l-valine residue. The synthetic natural products possessed potent antimycobacterial activity against Mtb with MIC90’s ranging from 110–360 nm and retained activity against Mtb in Mtb-infected macrophages. Deoxyecumicin also exhibited rapid bactericidal killing against Mtb, sterilizing cultures after 21 days.
Conformation-Enabled Total Syntheses of Ohmyungsamycins A and B and Structural Revision of Ohmyungsamycin B
Hur, Joonseong,Jang, Jaebong,Sim, Jaehoon,Son, Woo Sung,Ahn, Hee-Chul,Kim, Tae Sung,Shin, Yern-Hyerk,Lim, Changjin,Lee, Seungbeom,An, Hongchan,Kim, Seok-Ho,Oh, Dong-Chan,Jo, Eun-Kyeong,Jang, Jichan,Lee, Jeeyeon,Suh, Young-Ger
supporting information, p. 3069 - 3073 (2018/02/26)
The first total syntheses of the bioactive cyclodepsipeptides ohmyungsamycin A and B are described. Key features of our synthesis include the concise preparation of a linear cyclization precursor that consists of N-methyl amides and non-proteinogenic amino acids, and its macrolactamization from a bent conformation. The proposed structure of ohmyungsamycin B was revised based on its synthesis. The cyclic core of the ohmyungsamycins was shown to be responsible for the excellent antituberculosis activity, and ohmyungsamycin variants with truncated chains were evaluated for their biological activity.
Total Synthesis of Ecumicin
Hawkins, Paige M. E.,Giltrap, Andrew M.,Nagalingam, Gayathri,Britton, Warwick J.,Payne, Richard J.
, p. 1019 - 1022 (2018/02/23)
The first total synthesis of the potent anti-mycobacterial cyclic depsipeptide natural product ecumicin is described. Synthesis was achieved via a solid-phase strategy, incorporating the synthetic non-proteinogenic amino acids N-methyl-4-methoxy-l-tryptophan and threo-β-hydroxy-l-phenylalanine into the growing linear peptide chain. The synthesis employed key on-resin esterification and dimethylation steps as well as a final macrolactamization between the unusual N-methyl-4-methoxy-l-tryptophan unit and a bulky N-methyl-l-valine residue. The synthetic natural product possessed potent antimycobacterial activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC90 = 312 nM).
Asymmetric total synthesis and stereochemical revision of gymnangiamide
Tone, Hitoshi,Buchotte, Marie,Mordant, Celine,Guittet, Eric,Ayad, Tahar,Ratovelomanana-Vidal, Virginie
scheme or table, p. 1995 - 1997 (2009/09/08)
The asymmetric total synthesis of the originally proposed structure of gymnangiamide, a cytotoxic pentapeptide isolated from the marine hydroid Gymnangium regae Jaderholm, has been achieved. Key to the synthesis was the use of asymmetric hydrogenation of
A CD exciton chirality method for determination of the absolute configuration of threo-β-aryl-β-hydroxy-α-amino acid derivatives
Lo, Lee-Chiang,Yang, Chun-Tzu,Tsai, Charng-Sheng
, p. 1368 - 1371 (2007/10/03)
The absolute configuration of threo-β-aryl-β-hydroxy-α-amino acids was studied by CD exciton chirality method using 7-diethylaminocoumarin-3-carboxylate as a red-shifted chromophore. Bischromophoric derivatives for a series of threo-β-aryl-β-hydroxy-α-amino acids (3a-h) were prepared and their CD spectra measured in CH2Cl2. By combining the data of CD and NMR coupling constants, we are able to correlate their preferred conformer (B) and the positive CD to the corresponding (2S,3R)-absolute configuration. These results are consistent with those obtained from serine and threonine derivatives, which represent the simplest form of β-hydroxy-α-amino acids. This CD method could thus become a general method for determining the absolute configuration of threo-β-aryl-β-hydroxy-α-amino acids.
