Synthesis and assignment of the absolute configuration of the anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014

The synthesis of the spiroacetal-containing anti-Helicobacter pylori agents (3S,2'S,5'S,7'S)- (ent-CJ-12,954) and (3S,2'S,5'R,7'S)- (ent-CJ-13,014) has been carried out based on the convergent union of a 1:1 mixture of heterocycle-activated spiroacetal sulfones and with (3S)-phthalide aldehyde . The synthesis of the (3R)-diastereomers (3R,2'S,5'S,7'S)- and (3R,2'S,5'R,7'S)- was also undertaken in a similar manner by union of (3R)-phthalide aldehyde with a 1:1 mixture of spiroacetal sulfones and . Comparison of the (1)H and (13)C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2'S,5'S,7'S)- and (3S,2'S,5'R,7'S)- and the (3R)-diastereomers (3R,2'S,5'S,7'S)- and (3R,2'S,5'R,7'S)-, with the naturally occurring compounds, established that the synthetic isomers and were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014. The (2S,8S)-stereochemistry in protected dihydroxyketone , the precursor to the mixture of spiroacetal sulfones and was established via union of readily available (S)-acetylene with aldehyde in which the (4S)-stereochemistry was established via asymmetric allylation. Deprotection and cyclization of protected dihydroxyketone afforded an inseparable 1:1 mixture of spiroacetal alcohols and that were converted into a 1:1 inseparable mixture of spiroacetal sulfones and . Phthalide-aldehyde was prepared via intramolecular acylation of bromocarbamate in which the (3S)-stereochemistry was established via asymmetric CBS reduction of ketone .     

Asymmetric vinylogous Mannich reactions: a versatile approach to functionalized heterocycles

Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert-butyldimethylsilyloxy)furan (TBSOF, 1) with (R(S))- or (S(S))-t-BS-imines (3) furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g, which are, in turn, key intermediates for the synthesis of many bioactive compounds.     

Total stereoselective synthesis of (+)-goniothalesdiol

[reaction: see text] The stereoselective synthesis of (+)-goniothalesdiol (1) was accomplished in nine steps starting from commercially available (-)-(2S,3S)-dimethyl D-tartrate (3). The key features were a completely diastereoselective reduction of a beta-ketosulfoxide to generate the stereogenic center at C-5 in 7 and formation of the 2,5-cis-substituted tetrahydrofuran ring in 10 from a stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization/deoxygenation.     

吡咯烷生物碱及相关化合物的不对称合成研究(Ⅰ)

吡咯烷生物碱及相关化合物的不对称合成研究（Ⅰ）黄培强,阮源萍（厦门大学化学系,厦门,３６１００５）关键词Ｐｒｅｕｓｓｉｎ,４－氨基－３－羟基－５－苯基戊酸,不对称合成,酰胺－α－烷基化,１．５－二苄基－４－苄氧基－２－吡咯酮（＋）－ｐｒｅｕｓｓｉｎ１...     

Asymmetric Synthesis via Acetal Templates. 14. Preparation of Enantiomerically Pure (3S,4S)- and (3S,4R)-Statine Derivatives

Several (3S,4S)- and (3S,4R)-statine derivatives have been prepared by attack of nucleophiles on crystalline, epimeric N-BOC-lactams 7a and 7b. The key step in the synthesis of the lactams was the TiCl₄-catalyzed coupling reactions of acetals derived from (R)-1,3-butanediol with allyltrimethylsilane.

Several enantiometrically pure (3S,4S- and (3S, 4R)-statine derivatives were made by sodium cyanide-catalyzed reaction of nucleophiles with the lactams 3a and 3b which were synthesized by the scheme 1 → 2 → 3.     

Hyperfine splittings in spin-frustrated trinuclear Cu(3) clusters

The hyperfine structures of the EPR spectra of the spin-frustrated and distorted Cu(II) trimers were calculated in the spin-coupling model. The correlations between the hyperfine structures of the EPR spectra and geometry of the Cu(3) clusters (equilateral, isosceles, and scalene triangles) were found. For the EPR spectrum of the spin-frustrated ground state 2(S = 1/2) of an equilateral triangle Cu(3) cluster (J(12) = J(13) = J(23) = J), the calculated hyperfine structure represents the complicated spectrum of the 24 hyperfine lines, of total length 5a, where a is the hyperfine constant of the mononuclear Cu center. For an isosceles Cu(3) cluster (J(12) not equal J(13) = J(23)), the hyperfine splittings of the EPR spectra of the two split S = 1/2 levels with intermediate spins S(12) = 0 and S(12) = 1 are essentially different. The EPR signal of the |(S(12) = 0)S = 1/2> level is characterized by the four equally spaced hyperfine lines (interval A = a) with the same relative spectral amplitudes 16:16:16:16 and total length 3a. For the |(S(12) = 1)S = 1/2> level, the calculated hyperfine structure represents the spectrum of the 16 hyperfine lines with equal spacing (interval A' = a/3), the spectral intensity distribution 1:1:3:3:5:5:7:7:7:7:5:5:3:3:1:1 and total length 5a. These hyperfine spectra differ from the hyperfine structure (10 lines with interval a/3) of the EPR signals of the excited S = 3/2 level of the Cu(3) cluster. The quartet hyperfine structure, characteristic of a single Cu(2+) nucleus, which was observed experimentally for the doublet ground state of the spin-frustrated Cu(3)(II) clusters, corresponds to the hyperfine structure of the EPR signal of the |(S(12) = 0)S = 1/2> level. This hyperfine structure is evidence of the lowering of the Cu(3) cluster symmetry from trigonal to orthorhombic and the small splitting of the spin-frustrated 2(S = 1/2) ground state.     

Stereoselective synthesis of c3-c12 dihydropyran portion of antitumor laulimalide using copper-catalyzed oxonium ylide formation-[2,3] shift

Copper-catalyzed oxonium ylide formation-[2,3] shift of (5S,7R)-5-allyloxy-1-diazo-8-(p-methoxybenzyloxy)-7-methyl-2-octanone (3) proceeded in tetrahydrofuran-dichloromethane (4 : 1) under reflux with an excellent stereoselectivity (97 : 3) to give (2R,6S)-2-allyl-6-[(2R)-3-(p-methoxybenzyloxy)-2-methylpropyl]-3-dihydropyranone (2) as a major isomer in 82% yield. The resultant pyranone (2) was converted to the key intermediate (1) of the Mulzer's laulimalide synthesis and its derivatives (14, 15).     

Short,enantioselective total synthesis of okaramine N

The first enantioselective total synthesis of a member of the okaramine family of bis-indole alkaloids, okaramine N (1), has been accomplished via intermediates 2-7, as outlined. The N-prenylated derivative of (S)-tryptophan methyl ester (2) was coupled with Fmoc-protected N-tert-prenylated tryptophan (3) to form the amide 4 in 70% yield. Pd(II)-mediated cyclization/rearrangement, a key step in the synthesis, transformed 4 into the indoloazacine 5 (44%), which was deprotected and cyclized in a single step to give the hexacyclic diketopiperazine 6 (95%). In the following novel and key sequence, 6 was transformed into 1: (1) selective ene reaction with N-methyltriazolinedione, (2) photooxidation of the remaining tert-prenylated indole subunit to provide 7, and (3) thermal retroene reaction of 7 to afford okaramine N (70% from 6).     

Spirolactams as conformationally restricted pseudopeptides: synthesis and conformational analysis

The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.     

Synthesis of the spiroacetal-containing anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014

The first synthesis of the spiroacetal-containing anti-Helicobacter pylori agents ent-CJ-12,954 and ent-CJ-13,014 is reported based on the union of a heterocycle-activated spiroacetal-containing sulfone fragment with a phthalide-containing aldehyde fragment; comparison of the 1H and 13C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2"S,5"S,7"S)-(1a) and (3S,2"S,5"R,7"S)-(2a) and the (3R)-diastereomers (3R,2"S,5"S,7"S)-(1b) and (3R,2"S,5"R,7"S)- (2b) with the naturally occurring compounds established that the synthetic isomers (1a) and (2a) were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014.     

Cu_7S_4纳米管的生物分子辅助水热合成与光学性质(英文)

使用生物分子DL-甲硫氨酸辅助水热方法合成Cu7S4纳米管,产物的形貌与晶型可通过改变实验参数进行调控.研究表明,硝酸铜和DL-甲硫氨酸在反应开始时的配位比为1∶2,而且当反应物的摩尔比为1∶2和反应温度为200℃时可合成直径为100-600nm、长度达40-100μm的多晶Cu7S4纳米管.使用D-或L-甲硫氨酸均能得到类似Cu7S4纳米管.Cu7S4纳米管的禁带宽度为2.88eV,与Cu7S4的块体材料相比有明显蓝移.基于实验研究结果,讨论了甲硫氨酸分子中的官能团与反应产物之间的联系并提出了Cu7S4纳米管的自牺牲模板法形成机理.     

Synthesis of new [8Fe-7S] clusters: a topological link between the core structures of P-cluster, FeMo-co, and FeFe-co of nitrogenases

A coordinatively unsaturated dinuclear iron(II) complex of bulky thiolates, [(TipS)Fe(micro-SDmp)]2 (1; Tip = 2,4,6-(i)Pr(3)C(6)H(2), Dmp = 2,6-(mesityl)(2)C(6)H(3)), was synthesized from stepwise reactions of Fe{N(SiMe(3))2}2 with 1 equiv of HSDmp and then with 1 equiv of HSTip. Complex 1 was found to react with elemental sulfur (S8) in toluene to generate a new class of [8Fe-7S] cluster, [(DmpS)Fe(4)S(3)]2(micro-SDmp)2(micro-STip)(micro(6)-S) (2). The cluster 2 was also produced from one-pot reactions of Fe{N(SiMe(3))2}2 + HSDmp + HSTip + S8 (8:6:10:7/8) and Fe3{N(SiMe(3))2}2(micro-STip)4 + HSDmp + S8 (8/3:16/3:7/8), where another [8Fe-7S] cluster, [(TipS)Fe(4)S(3)]2(micro-SDmp)2{micro-N(SiMe(3))2}(micro(6)-S) (3), was also found as a minor byproduct. In either of the clusters, two Fe(4)S(3) incomplete cubane units are connected by three anionic ligands, namely three thiolate S atoms for 2 or two thiolate S atoms and one amide N atom for 3, and one hexa-coordinate S atom resides at the center of the [8Fe-7S] core. They have a common Fe(II)(5)Fe(III)3 oxidation states, and an S = 1/2 ground spin state was indicated by rhombic EPR signals at 10 K with g = 2.19, 2.07, and 1.96 for 2 and g = 2.13, 2.06, and 1.93 for 3. The structural relevance of clusters 2 and 3 to P-cluster, FeMo-co, and FeFe-co of nitrogenases is discussed.     

Synthesis and Crystal Structure of Ho_4S_3Si_2O_7

1 INTRODUCTION Halide fluxes are excellent media for growing single crystals of chalcogenides[1~5]. On our research in the Ln-Cu-Zn-Se system to find new phases and to search for potential infrared ceramic materials, two new compounds, KHo2CuSe4 and KEr2CuSe4, were synthesized from the reaction of the precursor with KCl flux[6]. In an attempt to synthesize the homologous sulfide by the same method using KBr as flux in a sealed evacuated quartz tube, single crystals of Ho4S3Si2O7 w…     

Shaping and enforcing coordination spheres: the implications of C3 and C1 chirality in the coordination chemistry of 1,1,1-tris(oxazolinyl)ethane ("trisox")

A key feature of tris(oxazolinyl)ethane ("trisox") ligands, which have shown broad scope in asymmetric catalysis, is the orientation and steric demand of their oxazoline substituents. This, along with the modularity of their synthesis determines their coordination chemistry. The possibility to combine oxazolines, in which the stereogenic centers adjacent to the N-donor atoms have different absolute configuration, whilst retaining their ability to coordinate as tripodal ligands, has been demonstrated by the synthesis of the enantiomerically pure C3-symmetric iPr-trisox(S,S,S) and C1-symmetric iPr-trisox(S,S,R) and their reaction with [Mo(CO)3(NCMe)3] yielding [Mo{iPr-trisox(S,S,S)}(CO)3] (1 a) and [Mo{iPr-trisox(S,S,R)}(CO)3] (1 b), respectively. The non-autocomplementarity of two homochiral trisox ligands at one metal center has been demonstrated by reaction of rac-C3 iPr-trisox with one equivalent of [Co(ClO4)2].6 H2O, giving the centrosymmetric heterochiral complex [Co(iPr-trisox)2](ClO4)2 (3), whereas an analogous reaction with the enantiopure ligand yielded a mixture of Co(II) complexes, which is characterized by the total absence of a [(trisox)2Co](+/2+) ion. The scope of the trisox ligand in terms of facial coordination to both early and late transition metals was demonstrated by the synthesis and structural characterization of the mononuclear complexes [ScCl3(iPr-trisox)] (4), [Fe(tBu-trisox)(NCMe)3](BF4)2 (5), and [Ru(eta6-p-cymene)(iPr-trisox)](PF6)2 (6). The facial coordination of their three ligating atoms to a metal center may be impeded if the transition-metal center stereoelectronically strongly favors a non-deltahedral coordination sphere, which is generally the case for the heavier d8-transition-metal atoms/ions. Reaction of iPr-trisox with [Rh(cod)2]BF4 led to the formation of the 16-electron d8-configured complex [Rh(iPr-trisox)(cod)](BF4) (7), which is oxidized by CsBr3 to give the Rh(III) complex [RhBr3(iPr-trisox)] (8) possessing a C3-symmetric structure with a kappa3-N-trisox ligand. The crystalline salts [M2(mu-Cl3)(iPr-trisox)2](PF6) (M=Fe(II): 9, Co(II): 10, Ni(II): 11), were prepared by addition of one molar equivalent of iPr-trisox and an excess of KPF6 to solutions of the anhydrous (FeCl2) or hydrated metal halides (CoCl2.6 H2O, NiCl2.6 H2O). All dinuclear complexes display weak magnetic coupling. For the mononuclear species [CuCl2(iPr-trisox)] (12) the removal of a chloride anion and thus the generation of a dinuclear chloro-bridged structure failed due to Jahn-Teller destabilization of a potential octahedral coordination sphere.     

Concise syntheses of cystothiazoles A, C, D, and melithiazol B

A convergent synthesis of cystothiazoles C 1 and D 3 was achieved based on Julia coupling between the functionalized aldehyde 5b, corresponding to left half of the final molecule, and aryl sulfone 6 or 7, bearing a bithiazole moiety, corresponding to right half. Methylation of 1 and 3 gave cystothiazole A 2 and melithiazol B 4, respectively. The overall yield (5 steps from (2R,3S)-3-methylpent-4-yne-1,2-diol 10; 57%) of 5b via the present route was improved in comparison to that of the previously reported functionalized aldehyde 5a (7 steps from 10; 13%). By applying the modified Julia coupling method, selectivity (6E/6Z=20 : 1-26 : 1) toward the (6E)-form of the coupled products (15 or 19) against the corresponding (6Z)-form was improved in comparison to the Wittig method (6E/6Z=4 : 1-6.9 : 1).     

Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.     

Efficient synthesis of enantiopure pyrrolizidinone amino acid

Enantiopure (3S,5R,8S)-3-[N-(Boc)amino]-1-azabicyclo[3.3.0]octan-2-one 8-carboxylic acid (1) was synthesized in nine steps and 16% overall yield from aspartate beta-aldehyde 7. Carbene-catalyzed acyloin condensation of 7, followed by acetylation and samarium iodide reduction, gave linear precursor (2S,7S)-alpha,omega-diamino-4-oxosuberate 11, which was converted to N-(Boc)aminopyrrolizidin-2-one carboxylic acid 1 by a reductive amination/lactam cyclization sequence. X-ray analysis of (3S,5R,8S)-methyl N-(Boc)aminopyrrolizidin-2-one carboxylate 21 showed that its internal backbone dihedral angles (psi = -149 degrees, phi = -49 degrees ) were in good agreement with the ideal values for a type II' beta-turn. Proton NMR experiments on N'-methyl-N-(Boc)aminopyrrolizidin-2-one carboxamide 23 demonstrated significantly different NH chemical displacements and temperature coefficients suggestive of solvent shielded and exposed hydrogens indicative of a turn conformation. Because pyrrolizidinone amino acids can serve as conformationally rigid dipeptide surrogates, this synthesis should facilitate their application in the exploration of conformation-activity relationships of various biologically active peptides.     

Reduced mono-, di-, and tetracubane-type clusters containing the [MoFe3S4]2+ core stabilized by tertiary phosphine ligation

Treatment of oxidized clusters [(Cl4cat)(MeCN)MoFe3S4Cl3]2- (1) and [(Meida)MoFe3S4Cl3]2- (2) with tertiary phosphines in the presence of NaBPh4 in acetonitrile results in chloride substitution at the iron sites and the formation of clusters with the reduced [MoFe3S4]2+ core. Thus, 1 is a precursor to [(Cl4cat)(MeCN)MoFe3S4(PR3)3] (R = But (3), Pri (4)) and [(Cl4cat)2(Et3P)2Mo2Fe6S8(PEt3)4] (5). Cluster 2 affords [[(Meida)MoFe3S4(PCy3)3]4Fe2(mu-Cl)L2]3+ (L = THF (6), MeCN (7)). The structures of 3-7 were established by X-ray analysis. Clusters 3 and 4 are single cubanes, centrosymmetric 5 (previously reported in a different space group: Demadis, K. D.; Campana, C. F.; Coucouvanis, D. J. Am. Chem. Soc. 1995, 117, 7832) is a double cubane with a rhomboidal Fe2S2 bridge, and 6 and 7 are tetracubanes. In the latter, four Meida oxygen atoms from different cubanes bind each of two central high-spin Fe(II) atoms in trans-Fe(mu-Cl)LO4 coordination. The topology of these clusters is not precedented. Zero-field M?ssbauer parameters for all clusters are reported. Isomer shift considerations suggest the formulation [Mo3+Fe2+2Fe3+S4] for reduced clusters. Voltammetry of 3 and 4 reveals four-member electron transfer series encompassing the oxidation levels [MoFe3S4]4+,3+,2+,+ in the potential interval + 1.0 to -1.3 V vs SCE in dichloromethane. Compared to the clusters with monoanionic ligands at the iron sites, phosphine ligation shifts redox potentials to more positive values. This effect arises from reduction of cluster negative charge and the tendency of phosphines to stabilize lower oxidation states. The synthesis of reduced clusters 4 from 1 and of [Fe4S4(PPri3)4]+ from [Fe4S4Cl4]2- is accompanied by the formation of Pri3PS, detected by 31P NMR, indicating that the phosphine is the reductant. This result implies a similar function of tertiary phosphines in the synthesis of 3 and 5-7. (Cl4cat = tetrachlorocatecholate(2-); Meida = N-methyliminodiacetate(2-).)     

基于偶氮苯酚类的比色传感器识别阴离子

设计合成了3个含酚羟基数量不同的偶氮苯化合物S1、S2和S3作为传感分子,研究S1、S2和S3对阴离子的比色识别,并探讨传感分子的结构与识别阴离子能力之间的联系。 结果表明:传感分子S1、S2和S3对F^-、H₂PO4-和AcO^-比色识别灵敏度高。 在CH₃CN中S1、S2和S3的F^-检测限达到1.25×10^-73.62×10^-7 mol/L,S2、S3对H₂PO4-和AcO^-的检测限也达同一数量级。 S1、S2和S3对阴离子F^-、H₂PO4-和AcO^-比色识别能力取决于阴离子的空间构型、电荷密度和碱性共同作用的结果。 ¹H NMR滴定结果表明,识别机理是S1、S2和S3的酚羟基与阴离子形成了分子间的氢键。     

Efficient and beta-Stereoselective Synthesis of 4(5)-(beta-D-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles(1)

A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.