Five-, six- and eight-membered ring organosilicon chalcogenides of the types Z2(SiMe2)2E (Z = Me2Si, H2C; E = S, Se, Te), Z(SiMe2E)2MR2 (Z = Me2Si, H2C, O; E = S, Se, Te; M = Si, Ge, Sn, R = Me, Ph) and (SiMe2ZSiMe2E)2 (Z = Me2Si, H2C; E = S, Se)

Reactions of ClMe₂Si–Z–SiMe₂Cl (Z = SiMe₂ (1a), CH₂ (1c), O (1e)) with Li₂E (E = S, Se) yielded eight-membered ring compounds (SiMe₂ZSiMe₂E)₂ (3a–d) as well as acyclic oligomers (SiMe₂ZSiMe₂E)_x of different chain lengths. If 1:1 molar mixtures of 1a, 1c or 1e and a diorganodichlorosilane, -germane or -stannane (R₂MCl₂) are reacted with Li₂E (E = S, Se, Te), six-membered ring compounds Z(SiMe₂E)₂MR₂ (4a–7g) are formed exclusively. Five-membered rings Z₂(SiMe₂)₂E (Z = SiMe₂ (8a–c), CH₂ (9a–c); E = S, Se, Te) are obtained starting from the tetrasilane ClMe₂Si–(SiMe₂)₂–SiMe₂Cl (1b) or the disilylethane ClMe₂Si–(CH₂)₂–SiMe₂Cl (1d) by treatment with Li₂E. All products were characterized by multinuclear NMR spectroscopy (¹H, ¹³C, ²⁹Si, ¹¹⁹Sn, ⁷⁷Se, ¹²⁵Te, including coupling constants) and the effects of the different ring sizes towards NMR chemical shifts are discussed.     

Novel stereoselective syntheses of (2E,4E)-4-(4,4-dimethylpent-2-ynylidene)-N1,N5-dimethyl-N1,N5-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine

We report two different synthetic approaches for the stereoselective synthesis of (2E,4E)-4-(4,4-dimethylpent-2-ynylidene)-N¹,N⁵-dimethyl-N¹,N⁵-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine 1, an important impurity-reference standard for the chemical characterization of terbinafine. The diamine 1 was obtained in only six steps with a good overall yield starting from commercially available glutaconic acid.     

Pheromone synthesis. Part 249: Syntheses of methyl (R,E)-2,4,5-tetradecatrienoate and methyl (2E,4Z)-2,4-decadienoate,the pheromone components of the male dried bean beetle,Acanthoscelides obtectus (Say)

The enantiomers of methyl (E)-2,4,5-tetradecatrienoate (1), a component of the male pheromone of Acanthoscelides obtectus, were synthesized from the enantiomers of 1-undecyn-3-ol (6), which were obtained via asymmetric acetylation of (±)-1-trimethylsilyl-1-undecyn-3-ol (4) with vinyl acetate as catalyzed by lipase PS (Amano). The ortho ester Claisen rearrangement of 6 with triethyl orthoacetate was the key-step to generate the chiral allenic system. A new synthesis of (±)-1 was also executed starting from (±)-6. Three different syntheses of methyl (2E,4Z)-2,4-decadienoate (2), another component of the male pheromone of A. obtectus, were achieved by means of either palladium-catalyzed Heck reaction or a Claisen and an Al₂O₃ catalyzed thermal rearrangements.     

Enzymatic desymmetrization of 2-amino-2-methyl-1,3-propanediol: asymmetric synthesis of (S)-N-Boc-N,O-isopropylidene-α-methylserinal and (4R)-methyl-4-[2-(thiophen-2-yl)ethyl]oxazolidin-2-one

We report herein, the novel enzymatic desymmetrization of 2-tert-butoxycarbonylamino-2-methyl-1,3-propanediol 1. This method makes it possible to prepare (S)-N-Boc-N,O-isopropylidene-α-methylserinal 3, which is a chiral building block for the synthesis of a variety of α-substituted alanine derivatives. Moreover, optically active (4R)-methyl-4-[2-(thiophen-2-yl)ethyl]oxazolidin-2-one 4, one of the key intermediates in the synthesis of a novel immunosuppressant, has been prepared by this methodology.     

Preparation,molecular structures,and characteristic properties of (E)-1-(2-furyl)- and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylenes and (E)-1-(3-furyl)- and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylenes

Wittig reactions of 2-furaldehyde (20) [and thiophene-2-carbaldehyde (21)] with (3-guaiazulenylmethyl)triphenylphosphonium bromide (19) in ethanol containing NaOEt at 25 °C for 24 h under argon give (E)-1-(2-furyl)-2-(3-guaiazulenyl)ethylene (22E) and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylene (23E) in 53 and 36% yields. Similarly, Wittig reactions of 3-furaldehyde (29) [and thiophene-3-carbaldehyde (30)] with 19 under the same reaction conditions as for 20 and 21 afford (E)-1-(3-furyl)-2-(3-guaiazulenyl)ethylene (31E) and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylene (32E) in 32 and 46% yields. Molecular structures and characteristic properties as well as preparation of the title E (i.e., one of the geometrical isomers) forms, with a view to comparative study, are reported. Moreover, reactions of those conjugated π-electron systems with TCNE (=tetracyanoethylene) in benzene [and in DMF (=N,N-dimethylformamide)] at 25 °C for 24 h under argon yield unique products, possessing interesting molecular structures, respectively, whose characteristic properties and crystal structures are documented, also.     

Preparation,crystal structure,and spectroscopic,chemical, and electrochemical properties of (2E,4E)-1,4-di(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-1,2-di(3-guaiazulenyl)ethylene

Wittig reaction of (E)-3-(3-guaiazulenyl)propenal (11) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (9) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title new (2E,4E)-1,3-butadiene derivative 4, in 33% isolated yield, which upon treatment with hexafluorophosphoric acid (i.e., 65% HPF₆ aqueous solution) in tetrahydrofuran (=THF) at 25 °C for 1 h under aerobic conditions affords a new air (two-electron) oxidation product (E)-ethylene-1,2-bis(3-guaiazulenylmethylium) bis(hexafluorophosphate) (14), quantitatively, and further, zinc-reduction of 14 in trifluoroacetic acid (=CF₃COOH) at 0 °C for 1 h under argon reverts 4, quantitatively. Along with the above interesting results, our discovered another preparation method, spectroscopic properties, crystal structure, and electrochemical behavior of 4, which serves as a strong two-electron donor and acceptor, compared with those of the previously reported (E)-1,2-di(3-guaiazulenyl)ethylene (3) are documented in detail.     

Collagen cross-links: a convenient synthesis of tert-butyl-(2S)-2-[(tert-butoxycarbonyl)amino]-4-(2-oxiranyl)butanoate

An efficient synthesis of tert-butyl-(2S)-2-[(tert-butoxycarbonyl)amino]-4-(2-oxiranyl) butanoate (5), the key intermediate for preparation of collagen cross-links (+)-pyridinoline (Pyd, 1) and (+)-deoxypyridinoline (Dpd, 2) was described from (4S)-5-(tert-butoxy)-4-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid (6) in six steps. Also, an improved synthesis of iodide (2S)-(−)-4b was presented.     

Bicyclo[2.2.2]octanes HC(SiMe2E)3MR (E=S, Se; M=Si, Ge, Sn; R=Me, Ph, Vi)

The reactions of 1:1 mixtures of the trisilylmethane HC(SiMe₂Cl)₃ (1b) and organo Group 14 trichlorides (RMCl₃, R=Me, Ph, vinyl (Vi); M=Si, Ge, Sn) with Li₂E (E=S, Se) in THF yielded the new bicyclo[2.2.2]octanes HC(SiMe₂E)₃MR (2a-6b). The products were identified by GC-MS and multinuclear NMR spectroscopy. Trends of the NMR data are discussed. The molecular structures of HC(SiMe₂S)₃SiMe (2a), HC(SiMe₂S)₃SiPh (3a), HC(SiMe₂Se)₃SiVi (4b) and HC(SiMe₂Se)₃GeMe (5b) are reported.     

Chemoenzymatic synthesis of (S)-2-cyanopiperidine,a key intermediate in the route to (S)-pipecolic acid and 2-substituted piperidine alkaloids

The preparation of (S)-2-cyanopiperidine 4 provides a new access to 2-substituted piperidines. This synthesis is based on an enantioselective (R)-oxynitrilase-catalyzed reaction for the preparation of (R)-(+)-6-bromo-2-hydroxyhexanenitrile 1 and the subsequent cyclization of this compound to yield the piperidine ring. The utilization of 4 as the starting material for the synthesis of (S)-2-aminomethylpiperidine 6, (R)-(−)-coniine 10 and (S)-(−)-pipecolic acid 13 is also described.     

Total synthesis of (4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles F

Total synthesis of (4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles F 3 was achieved from the chiral bithiazole-type primary alcohols [(S)- and (R)-4-ethoxycarbonyl-2′-(1-hydroxymethylethyl)-2,4′-bithiazoles 8], which were obtained based on the enzymatic resolution of racemic alcohol 8 and its acetate 9. From a direct comparison by means of chiral HPLC between natural cystothiazole F 3 and synthetic compounds [(4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles 3], natural cystothiazole F 3 was found to be a 33:67 diastereomeric mixture [(4R,5S,6E,14S)-3:(4R,5S,6E,14R)-3 = 33:67].     

Synthesis of dineophyltin dihydride and stereoselective hydrostannation of alkynes and (E)-trisubstituted alkenes

This paper reports the synthesis of dineophyltin dihydride (3) following two procedures. The four steps synthesis starting from benzyl chloride and Sn was shown to be more convenient than the two step direct alkylation of SnCl₄. The study of the free radical hydrostannation of mono- and disubstituted acetylenes with hydride 3 shows that they are stereoselective and that the stereoisomers obtained in higher proportion are stable and easily separated by column chromatography. Some preliminary studies on the chemical reactivity of the new divinylsubstituted dineophyltin compounds in Stille reactions are also informed. Radical hydrostannatation of (E)-trisubstituted ethylenes with 3 did not succeed probably due to steric factors. The preparation of dineophyltin bromohydride (27) is also reported. Radical addition of 27 to methyl (E)-2,3-disubstituted propenoates leads to mixtures of the corresponding erythro and threo adducts in diastereomeric excesses (d.e.) in the range of 74-90%.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Highly stereoselective synthesis of (2E,4E)-dienamides and (2E,4E)-dienoates via a double elimination reaction

Highly stereoselective synthesis of (2E,4E)-dienamides and (2E,4E)-dienoates was achieved through a double elimination reaction of β-acetoxy sulfones.     

Silylation as a protective method in acetylene chemistry. : Syntheses in the polyeneyne series,R3Si(CC)n(CHCH)4(CC)nSiR3 and H(CC)n(CHCH)4(CC)nH (n = 1, 2)

The Grignard reagents R₃Si(CC)_nMgBr (R = Me, n = 1; R = Et, n = 1,2) couple with cyclooctatetraene dibromide 1 in THF to give, as major products, the silyl-stabilised E, Z, Z, E-polyeneynes, Me₃SiCC(CHCH)₄CCSiMe₃3a, Et₃SiCC(CHCH)₄CCSiEt₃4a and Et₃Si(CC)₂(CHCH)₄(CC)₂SiEt₃6a together with minor proportions of configurational isomers Z, E, Z, Z 3c, all -E 3b, 4b, 6b and compounds in which a bicyclo-octadiene structure 2, 5 and 7 is retained. Irradiation converts the cis(Z)-rich isomers e.g. 3c into the all-trans(E) products. Treatment of the bissilyl compounds 3, 4 and 6 with aqueous base liberates the respective parent polyeneynes, H(CC)_n(CHCH)₄(CC)_nH, in each case.     

Stereoselective synthesis of tetrahydroisoquinoline alkaloids: (−)-trolline, (+)-crispin A, (+)-oleracein E

Tetrahydroisoquinoline alkaloids, (S)-(−)-trolline, (R)-(+)-crispin A, and (R)-(+)-oleracein E, have been synthesized stereoselectively from the both enantiomers of common intermediate (S)-4 and (R)-4. The key step in the synthesis include a stereoselective Bi(OTf)₃-catalyzed intramolecular 1,3-chirality transfer reaction of chiral non-racemic amino allylic alcohols (S)-6 and (R)-6 to construct both enantiomers of (E)-1-propenyl tetrahydroisoquinoline 4.     

Synthesis of (E)-2-chlorovinyltellurium trichloride and (E,E)-bis(2-chlorovinyl) ditelluride

The reaction of tellurium tetrachloride with acetylene in CCl₄ at atmospheric pressure and ambient temperature affords earlier unknown (E)-2-chlorovinyltellurium trichloride in 30% yield, whose reduction with sodium bisulfite gives (E,E)-bis(2-chlorovinyl) ditelluride in 64% yield.     

A short and efficient asymmetric synthesis of (1S,2R)-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride (UH-232)

A general practical asymmetric synthesis of (1S,2R)-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride (UH-232) was developed in a short and efficient method in high optical purity starting from commercially available 5-methoxy-1-tetralone. Asymmetric hydroboration of 5-methoxy-1-methyl-3,4-dihydronaphthalene with monoisopinocampheylborane followed by treatment with NaOH/H₂O₂ afforded key intermediate tetrahydronaphthol 4. Compound 4 was converted to the target molecule 1 using straightforward reactions.     

Total Synthesis of Amphidinolide E and Amphidinolide E Stereoisomers

Four amphidinolide E stereoisomers, amphidinolide E (1), 2-epi-amphidinolide E (2), 19-epi-amphidinolide E (3), and 2-epi-19-epi-amphidinolide E (4), have been synthesized via the judicious union of aldehyde 5, allylsilanes 7 or 8, acids 9 or 10, and vinylstannane 6. The C19 stereocenters of the C19 epimeric allylsilanes 7 and 8 were introduced via crotylboration reactions early in the synthesis. [3+2] Annulation reactions of aldehyde 5 with allylsilanes 7 and 8 were employed to set the core tetrahydrofuran units of 1-4. Finally, the C2 stereocenter was installed by esterification using acid 9, without incident, or with acid 10, in which case an unexpected and completely stereoselective inversion of C2 occurs.     

Synthesis,characterization, crystal structures, in vitro and in vivo antitumor activity of palladium(II) and zinc(II) complexes with 2-formyl and 2-acetyl pyridine N(4)-1-(2-pyridyl)-piperazinyl thiosemicarbazone

The present paper includes synthesis and spectral characterization of the novel prepared palladium(II) and zinc(II) complexes with 2-formyl pyridine N(4)-1-(2-pyridyl)-piperazinyl thiosemicarbazone, HFo4Npypipe, 1 and the 2-acetyl pyridine N(4)-1-(2-pyridyl)-piperazinyl thiosemicarbazone, HAc4Npypipe, 2. The Pd(II) complexes [PdCl(Fo4Npypipe)], 3, [PdCl(Ac4Npypipe)], 4 and the Zn(II) complexes [ZnCl₂(Fo4Npypipe)], 5 and [ZnCl₂(Ac4Npypipe)], 6 have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complexes [PdCl(Fo4Npippy)], 3 and [PdCl(Ac4Npippy)], 4, have been solved by single-crystal X-ray diffraction. The electronic, IR, UV/Vis, and NMR spectroscopic data of the complexes are reported. The results of the cytotoxic activity of 1–6 have been evaluated in vitro against the cells of three human cancer cell lines: MCF-7, T24, A-549 and a mouse L-929 (a fibroblast-like cell line cloned from strain L). For selected compounds 2 and 6 the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. The Zn(II) compounds 5 and 6 are considered as agents with potential antitumor activity, and can therefore be candidates for further stages of screening in vitro and/or in vivo.     

Spectroscopic,anti-bacterial,anti-cancer and molecular docking of Pd(II) and Pt(II) complexes with (E)-4-((dimethylamino)methyl)-2-((4,5-dimethylthiazol-2-yl)diazenyl)phenol ligand

New ligand (E)-4-((dimethylamino)methyl)-2-((4,5-dimethylthiazol-2-yl)diazenyl)phenol (HDmazo) was prepared by the coupling reaction between 4,5-dimethylthiazol-2-amine and 4-((dimethylamino)methyl)phenol. Moreover, the [MCl₂(HDmazo)] and [M(HDmazo)₂] [M^II = Pd and Pt] were prepared using the direct reaction of equivalent molar of HDmazo and Na₂PdCl₄ or K₂PtCl₄. The HDmazo and its complexes were investigated by different spectroscopic techniques. In complexes (1–2) HDmazo ligand behaves as bidentate style through the nitrogen of azo group and nitrogen of thiazole ring towards Pd(II) and Pt(II). Or in a bidentate fashion via the oxygen atom of the hydroxylate group and nitrogen atom of azo group as mono-anion in complexes (3–4). Further, the study of biological activity against four pathogenic bacteria showed that compound (3) exhibited good activity compared to other compounds. Additional the anti-tumor action against A2870 cell lines was screened, and the complexes (1) and (2) displayed good activity with 7.45 ± 0.98 µM and 13.23 ± 1.43 µM, respectively. The binding mechanism of the prepared compounds with EGFR tyrosine kinase, was investigated using molecular docking experiments.