6214-29-5

Upstream product

• 10443-65-9 2-bromo-2-propenoic acid 
• 124-41-4 sodium methylate 
• 34846-90-7 methyl 3-methoxyprop-2-enoate 
• 82290-07-1 ethyl ester of 3-methoxy-2-propen-1-oic acid 
• 60778-73-6 β-methoxyacrylic acid chloride 
• 600-05-5 2,3-dibromopropionic acid 
• 60838-50-8 3-methoxy-2-propenenitrile 
• 5788-17-0 methyl (2E)-3-methoxy-2-propenoate 
• 89125-55-3 2-chloro-1-methoxy-3-nitro-propane 
• 67-56-1 methanol 
• 54299-82-0 C₉H₁₇NO₂ 

Downstream Products

• 23130-58-7 3-(2,4-dinitro-phenylhydrazono)-propionic acid 
• 174230-82-1 β-methoxyacryloyl isocyanate 
• 926-61-4 3-oxopropanoic acid 
• 1005785-10-3 N-{5-[(2-{[(2E)-3-methoxyprop-2-enoyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]-2-methylphenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide 

Relevant academic research and scientific papers

From cyclopentadiene to isoxazoline-carbocyclic nucleosides: A rapid access to biological molecules through nitrosocarbonyl chemistry

A rapid access to carbocyclic nucleosides containing a fused isoxazoline ring is proposed starting from cyclopentadiene. The route involves an hetero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-O tether and elaboration of the heterocyclic aminols into nucleosides via linear construction of purine and pyrimidine heterocycles.

CARBOCYCLIC NUCLEOSIDES DERIVATIVES AND THE ANTIVIRUS COMPOSITIONS CONTAINING THE SAME

Carbocyclic nucleoside derivatives or pharmaceutically acceptable salts thereof are provided. The carbocyclic nucleoside derivatives or pharmaceutically acceptable salts thereof are represented by formula A or formula E. The descriptions of formulas A and E are the same as the contents described in the specification. The carbocyclic nucleoside derivatives which not only can effectively suppress virus by having a function of suppressing an SAH hydrolase, but also can be very appropriately used in suppression of virus and prevention and treatment of viral diseases since the carbocyclic nucleoside derivatives rarely have toxicity in body.COPYRIGHT KIPO 2020

Synthesis of 1′,2′-methano-2′,3′-dideoxynucleosides as potential antivirals

The synthesis of constrained nucleosides has become an important tool to understand the SAR in the interaction between biological and synthetic nucleotides in the context of antisense oligonucleotide therapy. The incorporation of a cyclopropane into a furanose ring of a nucleoside induces some degree of constrain without affecting significantly the steric environment of a nucleoside. Here, we report a new, short and stereocontrolled synthesis of two constrained nucleosides analogues, 1′,2′- methano-2′,3′-dideoxyuridine 9, and the corresponding cytidine analog 12. X-ray crystallography revealed that the furanose ring in the constrained uridine and cytidine analogues was flattened with virtual loss of pseudorotation. The phosphoramidate esters of the novel constrained uridine and cytidine nucleosides, intended as prodrugs, were tested in cell-based assays for viral replication across the herpes virus family and HIV inhibition courtesy of Merck laboratories, Rahway. They were also tested in antiproliferative assays against colorectal and melanoma cell lines. Unfortunately, none of the compounds showed activity in these assays.

Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against mycobacterium tuberculosis

DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. The compounds are highly bactericidal against extracellular as well as intracellular Mtb. Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. Compounds from this series are efficacious in various murine models of tuberculosis.

Genetically encoded unstrained olefins for live cell labeling with tetrazine dyes

A number of non-canonical amino acids (NCAAs) with unstrained olefins are genetically encoded using mutant pyrrolysyl-tRNA synthetase-tRNAPylCUA pairs. These NCAAs readily undergo inverse electron-demand Diels-Alder cycloadditions with tetrazine dyes, leading to selective labeling of proteins bearing these NCAAs in live cells. This journal is

Synthesis and molecular modeling of novel dihydroxycyclopentane- carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition

The regioisomeric cycloadducts of the bromonitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene were easily prepared and elaborated into a novel class of uracil nor-nucleoside derivatives. In the key-synthetic step represented by the reductive N-O bond cleavage, an unusual double ring opening afforded the aminol intermediates containing a β-hydroxynitrile structure. By adapting known protocols, the aminols entered the linear construction of uracil rings. These novel nucleosides were found structurally similar to a potent antiviral compound, Brivudin, and molecular modeling and docking allowed to select one of the two regioisomeric structures as promising candidate for antiviral tests, due to the nice level of binding with the Thymidine Kinase, the enzyme involved in virus replication.

From 1,3-cyclohexadiene through nitrosocarbonyl chemistry, the synthesis of pyrimidine isoxazoline-carbocyclic nucleosides

N-Benzoyl-2-oxa-3-azabicyclo[2.2.2]oct-5-ene undergoes cycloaddition with benzonitrile oxide affording a mixture of syn and anti regioisomeric cycloadducts. The anti cycloadducts were easily elaborated to stereodefined isoxazoline-carbocyclic aminols that served as synthons for the linear construction of pyrimidine nucleosides, while the syn cycloadducts do not enter the same synthetic route.

(E)-Selective hydrolysis of (E,Z)-α,β-unsaturated nitriles by the recombinant nitrilase AtNIT1 from Arabidopsis thaliana

From stereoisomeric α,β-unsaturated nitriles (E,Z)-1, the recombinant nitrilase AtNIT1 from Arabidopsis thaliana hydrolyses the (E)-isomers exclusively to the corresponding (E)-carboxylic acids (E)-2 with high specificity. The (E)-selectivity can also be utilised for the preparation of the isomerically pure nitriles (Z)-1. From (E,Z)-2-hydroxycinnamonitrile (E,Z)-3, the otherwise difficult obtainable (Z)-3 was prepared in 66% isolated yield. With β,γ-unsaturated (E,Z)-3-heptenenitrile (E,Z)-4, however, (E)-selectivity was not observed. AtNIT1 exhibits not only diastereoselectivity but also regioselectivity. From a mixture of the four isomers A-D of 3-(2-cyanocyclohex-3-enyl)propenenitrile 6, exclusively isomer D ((E)-cis-6) was hydrolysed to 3-(2-cyanocyclohex-3-enyl)propenoic acid (E)-cis-7, as stated by X-ray crystal structure. Only after complete conversion of D and high enzyme concentrations, isomer C ((E)-trans-6) was hydrolysed to a small extent.

A slightly shorter route to carbocyclic nucleosides. Synthesis of (±)- trans-1-[2-(hydroxymethyl)cyclopentylmethyl]uracil

(±)-trans-1-[2-(Hydroxymethyl)cyclopentylmethyl]uracil (1) was prepared in two steps and 56% yield from 2-hydroxymethylcyclopentylmethylamine (7) and 3-methoxy-2-propenoylisocyanate (6). Isocyanate 6 was prepared from methyl 3- methoxy-2-propenoate in four steps and 38% overall yield.

Total Synthesis of (±) carbocyclic polyoxin C and its α-epimer

Carbocyclic polyoxin C (2) and its α-epimer 3 were synthesized in racemic form in an efficient and diasteroedivergent fashion from cis-4-(N- tert-butylcarbamoyl)cyclopent-2-en-1-ol (5a). This synthesis features a Pd(0)-catalyzed substitution reaction, a novel, mild reduction of an α- nitro ester to an amino acid ester, and an improved procedure for uracil ring formation.