Ibrahim El-Sayed

Structure-Based Protein Engineering Efforts with a Monomeric Tim Variant: The Importance of a Single Point Mutation for Generating an Active Site with Suitable Binding Properties.

A monomeric variant of triosephosphate isomerase (TIM) with a new engineered binding groove has been characterized further. In this variant (ml8bTIM), the phosphate binding loop had been shortened, causing the binding site to be much more extended. Here, it is reported that in the V233A variant of ml8bTIM (A-TIM), three important properties of the wild-type TIM active site have been restored: (i) the structural properties of loop-7, (ii) the binding site of a conserved water molecule between loop-7 and loop-8 and (iii) the binding site of the phosphate moiety. It is shown that the active site of A-TIM can bind TIM transition state analogs and suicide inhibitors competently. It is found that the active site geometry of the A-TIM complexes is less compact and more solvent exposed, as in wild-type TIM. This correlates with the observation that the catalytic efficiency of A-TIM for interconverting the TIM substrates is too low to be detected. It is also shown that the A-TIM active site can bind compounds which do not bind to wild-type TIM and which are completely different from the normal TIM substrate, like a citrate molecule. The binding of this citrate molecule is stabilized by hydrogen bonding interactions with the new binding groove.

PREPARATION AND CHARACTERIZATION OF NEW C-SULFONYLDITHIOFORMATES AND THEIR THIOCARBONYL S-IMIDES

Abstract Two new chlorodithioformates 2, six new C-sulfonyldithioformates 3, ten new chloromethanesulfenyl chlorides 4, and nineteen new C-sulfonyldithioformate S-imides 5 have been prepared. Together with analogous known compounds they were fully characterized by spectroscopic means (IR, UV VIS, MS, 1C and 13C NMR). According to these data and additional X-ray crystallographic structure determinations of selected 5 all known 5 possess the (E)-configuration and no evidence for the presence of isomeric (Z)-5 could be found.

Synthesis of novel trithiocarbonate-S-oxides

The oxidation of the trithiocarbonates 3 with m-chloroperoxybenzoic acid (m-CPBA) in chloroform at room temperature provides an efficient stereoselective synthesis of the (E) sulfine 4 a and (Z) sulfine 4 b. The expected (E) and (Z) configurations of 4 a,b were confirmed by x-ray structure determination. The Sulfines 4 were further structurally elucidated by their cycloaddition reactions with 2,3-dimethyl-1,3-butadiene in chloroform at room temperature to give the corresponding dihydrothiopyran S-oxides 5 a,b in a quantitative yield.

The Chemistry of Chlorodithioformates

Abstract This review is the first exhaustive account of the preparation and synthetic application of chlorodithioformates, based on a CAS Online search. 106 compounds are presented and 187 literature references included.

Hetero-Diels-Alder reactions of chlorodithioformates with acyclic 1,3-dienes

At elevated temperatures chlorodithioformates 1 react with acyclic 1,3-dienes 2 with remarkable regioselectivity to yield 2 H -3,6-dihydrothiopyrans 3 . Spontaneous loss of HCl from 3 leads to the isolable but labile 2 H -thiopyrans 4 .

Chlorotropic rearrangements of an α-sulfanyl-α-sulfonylalkanesulfenyl chloride to an α-chloroalkyl disulfide and an S-(α-chloroalkyl) thiosulfonate

(1-Adamantylsulfonyl)(pentachlorophenylsulfanyl)chloromethanesulfenyl chloride, 3, can undergo two quantitative chlorotropic rearrangements, the more facile one leading to (1-adamantylsulfonyl)dichloromethyl pentachlorophenyl disulfide, 4, the less facile one forming S-[(pentachlorophenylsulfanyl)dichloromethyl] adamantane-1-thiosulfonate 5.

Chemistry of Sulfines, Part V: Chemo- and Stereoselective Synthesis and Hetero-Diels–Alder Reactions of Stable Sulfines

Abstract The stereoselective synthesis of a variety of Z-sulfines by the oxidation of organic trithiocarbonates with m-chloroperbenzoic acid (m-CPBA) is described. Transient E-sulfines that are formed upon heating of Z-sulfines during cycloaddition reactions were trapped with 2,3-dimethyl-1,3-butadiene to yield only one of the possible diastereomers of the functionalized cyclic allylic sulfoxides. An X-ray analysis and ab initio calculations were performed to provide insight into the steric course of the oxidation and cycloaddition reactions. [Supplementary materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional tables and figures.] GRAPHICAL ABSTRACT

C-Sulfonyldithioformates as heterodienophiles and enophiles in [4 + 2] cycloaddition and ene reactions

C-Sulfonyldithioformates 3 have been shown to be super-heterodienophiles in [4 + 2] cycloadditions with acyclic and cyclic dienes. Acyclic 1,3-dienes react with 3 in chloroform at room temperature to give the corresponding dihydrothiopyrans 4–6, while cyclopentadiene reacts with 3 to afford endo- and exo-2-thiabicyclo[2.2.1]heptene 7. Furthermore, the enophilic properties of 3 have been demonstrated by reacting 3 with tetramethylallene, 1-butene and trans-2-butene to afford the corresponding ene adducts 9, 10 and 11 respectively in quantitative yields.

Bioactive amide and α -aminophosphonate inhibitors for methicillin-resistant Staphylococcus aureus (MRSA)

Scaffolds of 2-acylamino-1,3,4-oxadiazole have been recently developed as transglycosylase inhibitors against MRSA. In the present study, structure–activity relationships of new derivatives of 2-acylamino-1,3,4-oxadiazole were explored with focus on the substitution of the aromatic rings. The in vitro antibacterial activity of these compounds against MRSA strain was evaluated using agar disc diffusion method. These inhibitors have an amide linker between 1,3,4-oxadiazole ring and the aromatic ring B. The role of this linker on the bioactivity of the compounds was also studied. The results showed promising series of 2-α-aminophosphonate-1,3,4-oxadiazole as inhibitors for MRSA strain. Both series revealed two structural features which appear to be essential for anti-MRSA activities, the first one is the incorporation of two electron-withdrawing groups at meta- and para- positions within aromatic ring B which contributed to a higher activity against MRSA strain. The second is the new α-aminophosphonate linker serving as bio-isosteric analogue of the corresponding amide linker and giving comparable results with the amide derivatives.Graphical abstract

A Comparative Study of the Effect of Water and Organic Solvents on 1,3-Dipolar Cycloaddition Reactions of Mesitonitrile Oxide with C-Sulfonyl- and Sulfanyl-Dithioformates

1,3-Dipolar cycloadditions of the C-sulfonylated- and sulfanylated-dithioformates with mesitonitrile oxide occurred smoothly in organic and aqueous media to afford 1,4,2-oxathiazoles in good yields. The structures of these cycloadducts have been established via the analysis of NMR data and elemental analyses.