90293-10-0

Upstream product

• 67-56-1 methanol 
• 121904-24-3 (S)_C(R)_P-2-<1-(2-methoxycarbonylpyrrolidyl)>-4H-1,3,2-benzadioxaphosphorin 2-sulfide 
• 96736-38-8 (R)-(-)-2,6-Dichloro-4-methylphenyl methyl phosphorochloridothionate 
• 90-01-7 salicylic alcohol 
• 90293-07-5 (-)-(R)-methyl p-nitrophenyl phosphorochloridothionate 
• 66084-67-1 2-chloro-4H-1,3,2-benzodioxaphosphorin 2-sulfide 
• 1329994-63-9 2-[(4S)-4-isopropyloxazolidin-2-on-3-yl]-4H-1,3,2-benzodioxaphosphorin-2-sulfide 

Relevant academic research and scientific papers

Linear synthesis of chiral cycloSal-pronucleotides

CycloSal-nucleosyl-phosphate triesters are a known class of highly effective nucleotide prodrugs (pronucleotides) of antivirally active nucleoside analogues. Until recently, the synthesis of these compounds always gave diastereoisomeric mixtures. Then, a convergent route for the stereospecific synthesis of cycloSal-triesters was described to give isomerically pure cycloSal-prodrugs for the treatment of viral diseases. Here, the development of a stereoselective synthesis of these pronucleotides using various chiral auxiliaries is described. In contrast to pyrrolidine- or pyrrolidinone derivatives it was found that a thiazolidine derived from valinol fulfilled all three requirements to act as a suitable chiral moiety, allowing: (i) strong chirality transfer, (ii) the formation of separable diastereoisomeric intermediates, and (iii) a suitable leaving group that allows the introduction of the nucleoside analogue (e.g., d4T) in the final step under mild reaction conditions. The title compounds were obtained with very high diastereoisomeric excesses of more than 95%. The development of a stereoselective route to cycloSal-nucleotides of thymidine and d4T based on the use of various chiral auxiliaries is reported. The target chiralphosphates were obtained with very high diastereoisomeric excesses of more than 95%.

ASYMMETRIC SYNTHESIS OF (Rp)- AND (Sp)-2-ETHYL-, (Rp)-2-PENTYLOXY-, (Sp)-2-PENTYLTHIO- AND (Sp)-2-PENTYLAMINO-4H-1,3,2-BENZODIOXAPHOSPHORIN 2-OXIDES

2-Substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides (2-substituted-BDPOs) are potent and stereoselective inhibitors of neuropathy target esterase (NTE) when the 2-substituent is n-alkyl, n-alkyloxy, n-alkylthio or n-alkylamino with maximum potency for the C7 to C9 analogs.Asymmetric syntheses were developed to assign the absolute configurations of each type of 2-substituted-BDPO. (Sp)-O-Methyl ethylphosphonothioic acid, the chiral starting material for (Rp)- and (Sp)-2-ethyl-BDPOs, was obtained by resolution of the racemate with quinine.It was > 82percent e.e. based on its stereospecific conversion to (Rp)-O-methyl ethylphosphonochloridothionate which was coupled with (Sc)-(-)-α-methylbenzylamine for analysis of the diastereomeric derivative by 1H and 31P NMR and HPLC.The final (Rp)- and (Sp)-2-ethyl compounds were 80 and 82percent e.e., respectively.The starting material for the chiral O-, S- and N-pentyl-BDPOs was (ScRp)-2--4H-1,3,2-benzodioxaphosphorin 2-sulfide which was recrystallized to 100percent d.e. (Rp)-2-Pentyloxy-BDPO (94percent e.e.) was obtained by two reaction sequences involving two or four steps. (Sp)-2-Pentylthio-BDPO (100percent e.e.) and (Sp)-2-pentylamino-BDPO (58 e.e.) were prepared in three- and five-step reactions, respectively.Optical purities were determined by HPLC with a CHIRALCEL OC column.In each asymmetric synthesis, the stereochemical orientation assigned for the substituents on phosphorus was consistent with the chromatographic characteristics on the chiral column. Key words: Asymmetric synthesis; 1.3.2-benzodioxaphosphorin 2-oxide; NTE inhibitors; stereochemistry.

Synthesis of Highly Pure Enantiomers of the Insecticide Salithion

Optically active salithion (>98percent e.e.) was obtained via an L-proline methyl ester derivative (PS), whose diastereomers were easily separated, with subsequent sulfuric acid-catalyzed methanolysis.The configuration of each diastereomeric PS was determ

Synthesis of Optically Active 1,3,2-Oxazaphospholidine 2-Sulfides and 1,3,2-Benzodioxaphosphorin 2-Sulfides

The optical isomers of ten kinds of insecticidal 1,3,2-oxazaphospholidine 2-sulfides (OS) and two kinds of 1,3,2-benzodioxaphosphorin 2-sulfides (BS), including the commercial insecticide salithion, were synthesized in high optical purity by using two optically active aryl methyl phosphorochloridothionates (AMPC) as chiral two-step phosphorylating reagents.Their configurations were assigned according to the reaction mechanism and supported by proton NMR information.

Synthesis of Optically Active Cyclic Phosphorothionates and Phosphoramidothionates with Insecticidal Activity by Using a Chiral Phosphorylating Agent

Chiral methyl p-nitrophenyl phosphorochloridothionate (MNPC) was utilized as a phosphorylating agent in the synthesis of optically active cyclic phosphorus esters including the enantiomers of 2-methoxy-4H-1,3,2-benzodioxaphosphorin 2-sulfide (salithion) and four diastereomers of 4-isobutyl-2-methoxy-1,3,2-oxazaphospholidine 2-sulfide (BMOS).Their insecticidal activity decreased in the following order; (S) > (R) in salithion and (S)P(S)C > (S)P(R)C > (R)P(R)C > (R)P(S)C in BMOS.