Category: 96929-05-4

Chen, Qi-Yin; Chaturvedi, Pravin R.; Luesch, Hendrik published the artcile< Process development and scale-up total synthesis of largazole, a potent class I histone deacetylase inhibitor>, COA of Formula: C12H18N2O4S, the main research area is macrocyclic depsipeptide natural product largazole total enantioselective synthesis; largazole anticancer agent histone deacetylase inhibitor drug design; hydrolysis fragment condensation Seebach procedure formylation methylation safety; Aldol condensation enzymic resolution peptide coupling macrocyclization cross metathesis.

Herein we describe the research and development of the process for the scale-up total synthesis of largazole, a potent class I selective histone deacetylase (HDAC) inhibitor, a potential anticancer agent and also useful for the treatment of other disorders where transcriptional reprogramming might be beneficial. The synthetic route and conditions for each fragment and final product were modified and optimized to make them suitable for larger-scale synthesis. With the process we developed, hundreds of grams of each fragment and decagrams of final product largazole were synthesized in good to excellent yields. The final target largazole was obtained in 21% overall yield over eight steps based on the longest sequence with over 95% HPLC purity.

Organic Process Research & Development published new progress about Aldol condensation. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, COA of Formula: C12H18N2O4S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Healy, Alan R.; Vizcaino, Maria I.; Crawford, Jason M.; Herzon, Seth B. published the artcile< Convergent and Modular Synthesis of Candidate Precolibactins. Structural Revision of Precolibactin A>, Application In Synthesis of 96929-05-4, the main research area is precolibactin convergent modular synthesis structure revision.

The colibactins are hybrid polyketide-nonribosomal peptide natural products produced by certain strains of commensal and extraintestinal pathogenic Escherichia coli. The metabolites are encoded by the clb gene cluster as prodrugs termed precolibactins. Clb+E. coli induce DNA double-strand breaks in mammalian cells in vitro and in vivo and are found in 55-67% of colorectal cancer patients, suggesting that mature colibactins could initiate tumorigenesis. However, elucidation of their structures has been an arduous task as the metabolites are obtained in vanishingly small quantities (μg/L) from bacterial cultures and are believed to be unstable. Herein we describe a flexible and convergent synthetic route to prepare advanced precolibactins and derivatives The synthesis proceeds by late-stage union of two complex precursors (e.g., 28 + 17 → 29a, 90%, represented in the graphic as I + II → III) followed by a base-induced double dehydrative cascade reaction to form two rings of the targets (e.g., 29a → 30a, 79%, III → IV). The sequence has provided quantities of advanced candidate precolibactins that exceed those obtained by fermentation, and is envisioned to be readily scaled. These studies have guided a structural revision of the predicted metabolite precolibactin A (to 7) and have confirmed the structures of the isolated metabolites precolibactins B (3) and C (6). Synthetic precolibactin C (6) was converted to N-myristoyl-D-asparagine and its corresponding colibactin by colibactin peptidase ClbP. The synthetic strategy outlined herein will facilitate mechanism of action and structure-function studies of these fascinating metabolites, and is envisioned to accommodate the synthesis of addnl. (pre)colibactins as they are isolated.

Journal of the American Chemical Society published new progress about Cyclocondensation reaction (base-induced double dehydrative cascade). 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Application In Synthesis of 96929-05-4.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Stress, Cedric J.; Sauter, Basilius; Schneider, Lukas A.; Sharpe, Timothy; Gillingham, Dennis published the artcile< A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles>, Quality Control of 96929-05-4, the main research area is DNA encoded library macrocycle compound; DNA chemistry; DNA-encoded libraries; Lipinski rules; chemical libraries; macrocycles.

Here the authors show a seven-step chem. synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed.

Angewandte Chemie, International Edition published new progress about Combinatorial library (DNA-encoded). 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Quality Control of 96929-05-4.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Pena, Stella; Scarone, Laura; Manta, Eduardo; Serra, Gloria published the artcile< First total synthesis of aerucyclamide B>, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate, the main research area is cyclic peptide aerucyclamide B total synthesis antimalarial agent fluorous; oxathiozole hydroxyamide cyclodehydration Deoxo Fluor peptide coupling fragment condensation; natural product Microcystis aeruginosa cyanobacteria.

The first total synthesis of the antimalarial aerucyclamide B has been achieved in 9% overall yield. Two thiazoles and a dipeptide were used to prepare two open precursors of cyclo-Gly-l-allo-Thr-l-Ile-Thz-d-allo-Ile-Thz. Cyclodehydration with Deoxo-Fluor of the β-hydroxyamide present in the macrocycle, rendered aerucyclamide B (67%) and an unexpected fluorous derivative (28%).

Tetrahedron Letters published new progress about Antimalarials. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Moody, Christopher J.; Bagley, Mark C. published the artcile< Total synthesis of (+)-nostocyclamide>, Recommanded Product: Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate, the main research area is nostocyclamide total synthesis.

A total synthesis of the naturally occurring macrocyclic bisthiazole-oxazole nostocyclamide is described.

Synlett published new progress about 96929-05-4. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Recommanded Product: Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Kikelj, D.; Urleb, U. published the artcile< Product class 17: thiazoles>, Quality Control of 96929-05-4, the main research area is review thiazole preparation.

A review of synthetic methods to prepare thiazoles as well as reactive modifications of thiazole moieties.

Science of Synthesis published new progress about Cyclization. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Quality Control of 96929-05-4.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ren, Qi; Dai, Lu; Zhang, Hui; Tan, Wenfei; Xu, Zhengshuang; Ye, Tao published the artcile< Total synthesis of largazole>, Recommanded Product: Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate, the main research area is largazole asym total synthesis.

The stereocontrolled total synthesis of largazole was accomplished starting from 3-[(tert-butyldimethylsilyl)oxy]propanol in 5.8% overall yield, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction, thiazoline-thiazole formation, and macrolactamization by use of the Mukaiyama reagent.

Synlett published new progress about Aldol addition, stereoselective. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Recommanded Product: Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Schmidt, Ulrich; Utz, Roland; Lieberknecht, Albrecht; Griesser, Helmut; Potzolli, Bernd; Bahr, Johanna; Wagner, Karin; Fischer, Peter published the artcile< Amino acids and peptides. 60. Synthesis of biologically active cyclopeptides. 10. Synthesis of 16 structural isomers of dolastatin 3. II. Synthesis of the linear educts and the cyclopeptides>, Category: thiazole, the main research area is dolastatin 3 isomer; structure dolastatin 3 NMR.

Sixteen isomers (I and II) of the cancerostatic cyclopeptide dolastatin 3 were synthesized. The proposed structure of dolastatin 3 is shown by 1H NMR spectrometry to be incorrect.

Synthesis published new progress about Isomers. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Category: thiazole.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Yu, Xiaoling; Zhang, Bingbing; Shan, Guangsheng; Wu, Yue; Yang, Feng-Ling; Lei, Xinsheng published the artcile< Synthesis of the molecular hybrid inspired by Largazole and Psammaplin A>, COA of Formula: C12H18N2O4S, the main research area is macrocyclic depsipeptide hybrid thiol synthesis HDAC inhibitor antitumor agent; natural product largazole psammaplin A drug design; methylcysteine acylation cyclocondensation thiazole thiazoline hydrolysis; malic acid cyclocondensation trichloro ethanediol esterification amidation; macrolactamization protective group.

One important class of HDAC (histone deacetylation enzymes) inhibitors is the sulfur-containing marine natural products with structural diversity. Inspired by two structurally distinguishing examples, Largazole and Psammaplin A, which possess macrocyclic depsipeptide and simple linear amide scaffold resp., we designed one novel mol. hybrid by replacing the alkene moiety in Largazole with a semirigid amide bond. This hybrid compound has been synthesized from L-malic acid in 10 steps with an overall yield of 7%. The preliminary biol. assays suggest that the replacement of trans olefin moiety with amide bond will lead to an unbeneficial effect on the inhibition against HDACs.

Tetrahedronpublished new progress about (Fluorenylmethoxy)carbonyl group. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, COA of Formula: C12H18N2O4S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Pena, S.; Fagundez, C.; Medeiros, A.; Comini, M.; Scarone, L.; Sellanes, D.; Manta, E.; Tulla-Puche, J.; Albericio, F.; Stewart, L.; Yardley, V.; Serra, G. published the artcile< Synthesis of cyclohexapeptides as antimalarial and anti-trypanosomal agents>, Formula: C12H18N2O4S, the main research area is cyclohexa peptide synthesis antimalarial antitrypanosomal agent structure activity; solid phase peptide synthesis macrocyclization.

Cyclohexapeptide analogs of natural products were obtained in very good yields by a combination of solid-phase peptide synthesis, for the linear peptide, and solution cyclization. The activities against Plasmodium falciparum K1, Trypanosoma brucei brucei and murine macrophages (cell line J774) of these novel compounds and azolic macrocycles, previously reported by us, were evaluated. Seven macrocycles showed submicromolar activities against Plasmodium falciparum K1 and a high selectivity (SI > 125) for the parasite. In addition, two compounds displayed one digit micromolar EC50 against T. brucei brucei and satisfactory selectivity (SI 82 and 95). Preliminary structure-activity relationships are presented.

MedChemCommpublished new progress about Antimalarials. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Formula: C12H18N2O4S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica