4871-14-1

Upstream product

• 51-21-8 5-fluorouracil 
• 106-95-6 allyl bromide 
• 17242-85-2 5-fluoro-2,4-bis(trimethylsilyloxy)pyrimidine 
• 591-87-7 Allyl acetate 
• 107-18-6 allyl alcohol 
• 118004-30-1 Carbonic acid 3-allyl-5-fluoro-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl ester benzyl ester 

Downstream Products

• 51-21-8 5-fluorouracil 
• 877621-34-6 5-fluoro-1-({(3S,5R)-2-[5-O-(tert-butyldiphenylsilyl)-2,3-O-isopropylidene-β-D-ribofuranosyl]-3-(hydroxymethyl)-1,2-isoxazolidin-5-yl}methyl)pyrimidine-2,4(1H,3H)-dione 
• 877621-27-7 ethyl (3S,5R)-2-[5-O-(tert-butyldiphenylsilyl)-2,3-O-isopropylidene-β-D-ribofuranosyl]-5-[(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]isoxazolidine-3-carboxylate 

Relevant academic research and scientific papers

General Strategy for Integrated Bioorthogonal Prodrugs: Pt(II)-Triggered Depropargylation Enables Controllable Drug Activation in Vivo

Bioorthogonal decaging reactions for controllable drug activation within complex biological systems are highly desirable yet extremely challenging. Herein, we find a new class of Pt(II)-triggered bioorthogonal cleavage reactions in which Pt(II) but not Pt(IV) complexes effectively trigger the cleavage of O/N-propargyl in a variety of ranges of caged molecules under biocompatible conditions. Based on these findings, we propose a general strategy for integrated bioorthogonal prodrugs and accordingly design a prodrug 16, in which a Pt(IV) moiety is covalently connected with an O2-propargyl diazeniumdiolate moiety. It is found that 16 can be specifically reduced by cytoplasmic reductants in human ovarian cancer cells to liberate cisplatin, which subsequently stimulates the cleavage of O2-propargyl to release large amounts of NO in situ, thus generating synergistic and potent tumor suppression activity in vivo. Therefore, Pt(II)-triggered depropargylation and the integration concept might provide a general strategy for broad applicability of bioorthogonal cleavage chemistry in vivo.

BIOORTHOGONAL METHODS AND COMPOUNDS

The invention provides a new bioorthogonal deprotection method for preparing heterocyclic compounds by bond cleavage using palladium. The methods have general application in the field of biological synthetic chemistry. Compounds, such as prodrugs, which are useful in such methods are also provided.

One-pot synthesis of n-alkyl purine, pyrimidine and azole derivatives from alcohols using ph3p/ccl4: A rapid route to carboacyclic nucleoside synthesis

A facile and efficient method for one-pot N-alkylation of nucleobases and azole derivatives from alcohols using triphenylphosphine in carbon tetrachloride is described. In this method, treatment of alcohols with a mixture of triphenylphosphine, carbon tetrachloride, nucleobase or azole derivatives and potassium carbonate in the presence of catalytic amounts of tetra-n- butylammonium iodide (TBAI) in refluxing N,N-dimethylformamide, furnishes the corresponding N-alkyl derivatives in good yields. This methodology is highly efficient for various structurally diverse primary alcohols and also useful for N-alkylation of other N-heterocycles containing an acidic N-H bond.

One-pot synthesis of N-alkyl purine and pyrimidine derivatives from alcohols using TsIm: a rapid entry into carboacyclic nucleoside synthesis

A convenient and efficient one-pot N-alkylation of nucleobases from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, treatment of alcohols with a mixture of purine or pyrimidine nucleobase, TsIm, K2CO3, and triethylamine in refluxing DMF regioselectively furnishes the corresponding N-alkyl nucleobases in good yields. This methodology is highly efficient for various structurally diverse primary alcohols.

Efficient synthesis of various acycloalkenyl derivatives of pyrimidine using cross-metathesis and Pd(0) methodologies

Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) have been prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, while the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. The cross-metathesis performed with a ruthenium catalyst was used to provide new acycloalkenyl nucleosides. The antiviral activities of all final compounds have been evaluated. Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) were prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, meanwhile the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. A ruthenium-based cross-metathesis reaction was used to synthesize new acycloalkenyl nucleosides.

SYNTHESIS OF (3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL) DERIVATIVES OF HETEROCYCLIC BASES

Analogs of antiviral 9-(S)-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA, I), containing modofied heterocyclic base, were prepared from racemic or (S)-N-(2,3-dihydroxypropyl) derivatives II.Compounds II are heated with chloromethylphosphonyl dichlor

Application of the Benzyloxycarbonyloxymethyl Moiety to a Protective Group of 5-Fluoroacil. Selective Alkylation of Amide Nitrogen of the Uracil Ring

Selective alkylation of 5-fluorouracil using the benzoyloxycarbonyloxymethyl moiety as a protective group of amide nitrogen of the uracil ring is described.Protection, alkylation and deprotection were carried out in high yields.