4248-74-2

Usage

InChI:InChI=1/C9H18O8S2/c1-9(2)16-7(5-14-18(3,10)11)8(17-9)6-15-19(4,12)13/h7-8H,5-6H2,1-4H3/t7-,8-/m0/s1

Upstream product

• 59779-75-8 diethyl (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate 
• 25432-12-6 2,3-O-Isopropyliden-DL-threitol 
• 124-63-0 methanesulfonyl chloride 
• 116499-08-2 dimethyl 2,2-dimethyl-1,3-dioxolane-trans-4,5-dicarboxylate 
• 50622-09-8 2,3-O-isopropylidene-L-threitol 
• 37031-29-1 (-)-dimethy-2,3-O-isopropylidene-L-tartrate 

Downstream Products

• 299-74-1 treosulfan 
• 32305-98-9 (-)-Diop 
• 98253-70-4 (-)-2,2-dimethyl-4,5-bis(phenylsulfanylmethyl)-1,3-dioxolane 
• 119322-88-2 ((4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanamine 
• 299-74-1 DL-Threitol-1,4-bis-methansulfonat 

Relevant academic research and scientific papers

Concise synthesis of: N -phosphorylated amides through three-component reactions

N-Phosphorylated amides continue to be an unparalleled asset for the development of pharmaceutical molecules, and the importance of this framework has inspired researchers to look for concise and efficient methods for the synthesis of this unit. In this work, a new strategy was developed in which a one-pot synthesis of N-phosphorylated amides was achieved by a three-component reaction with carboxylic acids, phosphorus chlorides and azides under mild reaction conditions. To our knowledge, this is the first study in which this framework was constructed through a multicomponent reaction, which is innovative, efficient and economical. This journal is

Combination of chemotherapy and oxidative stress to enhance cancer cell apoptosis

Cancer cells are vulnerable to reactive oxygen species (ROS) due to their abnormal redox environment. Accordingly, combination of chemotherapy and oxidative stress has gained increasing interest for the treatment of cancer. We report a novel seleno-prodrug of gemcitabine (Gem), Se-Gem, and evaluated its activation and biological effects in cancer cells. Se-Gem was prepared by introducing a 1,2-diselenolane (a five-membered cyclic diselenide) moiety into the parent drug Gemvia a carbamate linker. Se-Gem is preferably activated by glutathione (GSH) and displays a remarkably higher potency than Gem (up to a 6-fold increase) to a panel of cancer cell lines. The activation of Se-Gem by GSH releases Gem and a seleno-intermediate nearly quantitatively. Unlike the most ignored side products in prodrug activation, the seleno-intermediate further catalyzes a conversion of GSH and oxygen to GSSG (oxidized GSH) and ROS via redox cycling reactions. Thus Se-Gem may be considered as a suicide agent to deplete GSH and works by a combination of chemotherapy and oxidative stress. This is the first case that employs a cyclic diselenide in prodrug design, and the success of Se-Gem as well as its well-defined action mechanism demonstrates that the 1,2-diselenolane moiety may serve as a general scaffold to advance constructing novel therapeutic molecules with improved potency via a combination of chemotherapy and oxidative stress.

Chiroptical properties of 2,2’-bioxirane

The two enantiomers of 2,2′-bioxirane were synthesized, and their chiroptical properties were thoroughly investigated in various solvents by polarimetry, vibrational circular dichroism (VCD), and Raman optical activity (ROA). Density functional theory (DFT) calculations at the B3LYP/aug-cc-pVTZ level revealed the presence of three conformers (G+, G?, and cis) with Gibbs populations of 51, 44, and 5% for the isolated molecule, respectively. The population ratios of the two main conformers were modified for solvents exhibiting higher dielectric constants (G? form decreases whereas G+ form increases). The behavior of the specific optical rotation values with the different solvents was correctly reproduced by time-dependent DFT calculations using the polarizable continuum model (PCM), except for the benzene for which explicit solvent model should be necessary. Finally, VCD and ROA spectra were perfectly reproduced by the DFT/PCM calculations for the Boltzmann-averaged G+ and G? conformers.

Turning the Nitrogen Atoms of an Ar2P?CH2?N?N?CH2?PAr2 Motif into Uniquely Configured Stereocenters: A Novel Diphosphane Design for Asymmetric Catalysis

Hexahydropyridazines with CH2PAr2 groups at both N atoms are newly designed 1,4-diphosphanes and were synthesized for the first time. Their N atoms assume a single configuration under the influence of stereocenters at C-5 and C-6. In the solid state, these N-atoms bind the CH2PAr2 substituents axially. Combined with Pd0, N,N′-chiral diphosphanes of this kind catalyzed Tsuji–Trost type allylations of dialkyl malonates with racemic 1,3-diphenylallyl acetate efficiently and with up to 91 % ee.

Enantioselective α-Hydroxylation by Modified Salen-Zirconium(IV)-Catalyzed Oxidation of β-Keto Esters

The highly enantioselective α-hydroxylation of β-keto esters using cumene hydroperoxide (CHP) as the oxidant was realized by a chiral (1S,2S)-cyclohexanediamine backbone salen-zirconium(IV) complex as the catalyst. A variety of corresponding chiral α-hydroxy β-keto esters were obtained in excellent yields (up to 99%) and enantioselectivities (up to 98% ee). The zirconium-catalyzed enantioselective α-hydroxylation of β-keto esters was scalable, and the zirconium catalyst was recyclable. The reaction can be performed in gram scale, and corresponding chiral products were acquired in 95% yield and 99% ee.

Ring-opening and -expansion of 2,2′-biaziridine: Access to diverse enantiopure linear and bicyclic vicinal diamines

The chiral pool-derived 1,1′-ditosyl-2,2′-biaziridine has been established as a valuable building block for the divergent synthesis of enantiopure vicinal diamines. Efficient procedures for the regioselective ring opening of the biaziridine with oxygen, sulfur, nitrogen, and carbon nucleophiles are described. The strategic use of nucleophiles bearing pendant functionality allows further elaboration of the acyclic products to a variety of 2,2′-bicyclic-embedded diamines. Desymmetrization of the biaziridine has also been accomplished via the selective monoaddition of organocuprates.

Interstrand and intrastrand DNA-DNA cross-linking by 1,2,3,4-diepoxybutane: Role of stereochemistry

1,2,3,4-Diepoxybutane (DEB) is a bifunctional electrophile capable of forming DNA-DNA and DNA-protein cross-links. DNA alkylation by DEB produces N7-(2′-hydroxy-3′,4′-epoxybut-1′-yl)-guanine monoadducts, which can then form 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) lesions. All three optical isomers of DEB are produced metabolically from 1,3-butadiene, but S,S-DEB is the most cytotoxic and genotoxic. In the present work, interstrand and intrastrand DNA-DNA cross-linking by individual DEB stereoisomers was investigated by PAGE, mass spectrometry, and stable isotope labeling. S,S-, R,R-, and meso-diepoxides were synthesized from L-dimethyl-2,3-O-isopropylidene-tartrate, D-dimethyl-2,3-O-isopropylidene- tartrate, and meso-erythritol, respectively. Total numbers of bis-N7G-BD lesions (intrastrand and interstrand) in calf thymus DNA treated separately with S,S-, R,R-, or meso-DEB (0.01-0.5 mM) were similar as determined by capillary HPLC-ESI+-MS/MS of DNA hydrolysates. However, denaturing PAGE has revealed that S,S-DEB produced the highest number of interchain cross-links in 5′-GGC-3′/3′-CCG-5′ sequences. Intrastrand adduct formation by DEB was investigated by a novel methodology based on stable isotope labeling HPLC-ESI+-MS/MS. Meso DEB treatment of DNA duplexes containing 5′-[1,7, NH2-15N3,2- 13C-G]GC-3′/3′-CCG-5′ and 5′-GGC-3′/ 3′-CC[15N3,2-13C-G]-5′ trinucleotides gave rise to comparable numbers of 1,2-intrastrand and 1,3-interstrand bis-N7G-BD cross-links, while S,S DEB produced few intrastrand lesions. R,R-DEB treated DNA contained mostly 1,3-interstrand bis-N7G-BD, along with smaller amounts of 1,2-interstrand and 1,2-intrastrand adducts. The effects of DEB stereochemistry on its ability to form DNA-DNA cross-links may be rationalized by the spatial relationships between the epoxy alcohol side chains in stereoisomeric N7-(2′-hydroxy-3′,4′-epoxybut-1′-yl)- guanine adducts and their DNA environment. Different cross-linking specificities of DEB stereoisomers provide a likely structural basis for their distinct biological activities.

Phosphine-borane complexes; Direct use in asymmetric catalysis

An easy and soft method of decomplexation of phosphine-borane complexes, by DABCO, allows its use in situ in asymmetric catalytic hydrogenation of double bonds with metal phosphine complexes.

Synthesis of chiral nonracemic diols via nucleophilic opening of (S,S)-1,2,3,4-diepoxybutane

(S,S)-1,2,3,4-diepoxybutane was synthesized from (R,R)-dimethyl tartrate. Nucleophilic opening of this diepoxybutane gave a convenient method for generating a variety of chiral nonracemic diols.