Convergent total syntheses of callipeltosides a, B, and C

Going for the hat-trick: The synthesis of the entire callipeltoside family of natural products is described. Key to this synthesis was the coupling of the di-ene-yne and pyran fragments by a diastereoselective alkenylzinc addition allowing rapid access to the common aglycon. Attachment of each relevant L-configured sugar resulted in the first total synthesis of callipeltoside B, and the syntheses of callipeltosides?A and C.     

High-Yielding Enantioselective Synthesis of the Macrolactam Aglycon of Sch 38516 from Two Units of (2R)-2-Ethyl-4-penten-1-ol

The same precursor —namely, (2R)-2-ethyl-4-penten-1-ol—was used to obtain fragments C9–C13 and C1–C8 of 1 , the aglycon of Sch 38516 (which is active against Candida sp.) and fluvirucin B₁ (which is active against influenza A virus). The key steps of the synthesis were the aldol-like reaction between the two fragments and the macrolactamization of a 13-azidotridecanoic acid derivative (see scheme). MOM=methoxymethyl, Py=2-pyridyl.     

Comprehensive synthesis of ER related high-mannose-type sugar chains by convergent strategy

Systematic synthesis of high-mannose-type sugar chains of asparagine-linked glycoproteins is described. To construct the target sugar chains, we employed the convergent route, using three oligosaccharide components, the common hexasaccharide, branched tri-, tetra- and pentasaccharides, and mono-, di-, and triglucosyl fragments. Construction of the β-mannoside linkage was performed using p-methoxybenzyl-assisted intramolecular aglycon delivery. The hexasaccharide fragment was coupled with the branched mannooligosaccharide donors such as M5, M4B, M4C, and M3 to give undecasaccharide (M9), decasaccharide (M8B and M8C), and nonasaccharide (M7), respectively. Incorporation of mono-, di-, and triglucosyl fragments toward them gave tetradecasaccharide (G3M9), tridecasaccharide (G2M9), dodecasaccharide (G1M9), undecasaccharide (G1M8B and G1M8C), and decasaccharide (G1M7), respectively.     

A formal synthesis of the auriside aglycon

A highly convergent formal synthesis of the auriside aglycon was achieved. An indene-based thiazolidinethione chiral auxiliary was used for the construction of both the C1-C9 and C10-C17 fragments via acetate aldol reactions. A Meinwald reaction was utilized to install the stereocenter at C2, and a conjugated addition to an ynone was used to construct the C9-C11 enone.     

Newly designed Mn (III)–W(V) bimetallic assembly built by manganese (III) Schiff–base and octacyanotungstate(V) building blocks: Structural topologies,and magnetic features

New complex [Mn (SB)₂(DMF)₂] [W (CN)₈] hereafter referred to as complex 1 , which was prepared by self–assembly of [Mn (SB)₂(DMF)₂]³⁺ and [W (CN)₈]³⁻ and structurally characterized by elemental analysis, infrared (IR) and single crystal X–ray techniques (H₂SB is Schiff base derived from the condensation of salicylaldehyde and N,N–diethylethylenediamine and DMF is dimethylformamide). The structure consists of 1–D supramolecular chains and further stacks to give a 3–D supramolecular architecture whose molecular fragments are linked by hydrogen bond as well as C − H···π interactions between [Mn (SB)₂(DMF)₂]³⁺ and [W (CN)₈]³⁻. An underlying net for the representation consists of two types of fragments with 1,4 M5–1 and 1,8 M9–1 topologies and further illustration of the molecular network in terms of a graph−theory approach using simplification procedure resulted in the underlying net of 2C1topological type in the complex 1 . Magnetic susceptibility measurements of complex 1 was carried out in the temperature range 2–300 K, indicates the presence of either magnetic anisotropy zero field splitting, the effect of intramolecular interactions, or both. Complex 1 follows the Curie–Weiss law with Curie constant value of 3.43 cm³mol⁻¹K, and the slight negative Weiss constant (−0.60 K) value indicates the predominant antiferromagnetic magnetic exchange interactions. The magnetic properties of Title complex was investigated thoroughly and showed that ferromagnetic interaction between W(V) and Mn (III) operate via the intramolecular H–bonding interaction between cyanide nitrogens and a hydrogen atom.     

Comprehensive 1H and 13C NMR assignment of 13 protobassic acid saponins

This study aimed to carry out complete ¹H and ¹³C NMR assignment of 13 protobassic acid saponins, including arganins A–C ( 1 – 3 ) and F ( 4 ), butyrosides B–D ( 5 – 7 ), tieghemelin ( 8 ), 3′-O-glucosyl-arganin C ( 9 ), Mi-saponins A–C ( 10 – 12 ), and mimusopsin ( 13 ), recorded in methanol-d₄. This was accomplished by the analysis of high-resolution one-dimensional (1D) NMR (¹H and ¹³C), two-dimensional (2D) NMR (¹H–¹H COSY, HSQC, and HMBC), and selectively excited 1D TOCSY spectra. Before this study, ¹H and ¹³C NMR data of arganins A–C ( 1 – 3 ) and F ( 4 ) were partially assigned. Our effort leads to their complete assignment, especially the glycon residue, and revises some reported data. Some revisions of the ¹H and ¹³C NMR data in the glycon part of butyroside C ( 6 ), tieghemelin ( 8 ), Mi-saponin A ( 10 ), and mimusopsin ( 13 ) were made. Those data of butyrosides B and D ( 5 & 7 ) and Mi-saponin B ( 11 ), which had not been recorded in methanol-d₄, are provided. In addition, the ¹H and ¹³C NMR data of Mi-saponin C ( 12 ) are reported for the first time. These data, being recorded in methanol-d₄, should be more friendly for use as a reference for identifying the related triterpenoid saponins.     

Metal‐induced B–H Activation. Addition of Methyl Acetylene Carboxylates to Cp*Rh‐ and Cp*Ir 16 e Halfsandwich Complexes containing a Chelating 1,2‐Dicarba‐closo‐dodecaborane‐1,2‐diselenolato Ligand

Reactions of the 16e halfsandwich complexes Cp*M[Se₂C₂(B₁₀H₁₀)] ( 5 M = Rh, 6 M = Ir) with both methyl acetylene monocarboxylate and dimethyl acetylene dicarboxylate were studied in order to obtain information on the influence of the chalcogen (selenium versus sulfur), as well as further evidence for B–H activation, ortho‐metalation and substitution of the carborane. In the case of the rhodium‐selenium complex 5 , the reaction with methyl acetylene monocarboxylate gave products which were all structurally different compared to those of the sulfur analogue of 5 : a polycyclic derivative 12 with a B(6)‐substituted carborane cage was obtained as one of the final products; in addition, both geometrical isomers containing a Rh–B bond ( 10 , 11 ) and isomers without a Rh–B bond ( 8 , 9 ) were isolated, the latter being the result of twofold insertion into one of the Rh–Se bonds. In the case of the iridium‐selenium complex 6 , the reaction with methyl acetylene monocarboxylate led to the geometrical isomers 13 and 14 (similar to 10 and 11 ) with structures possessing an Ir–B bond. Both 5 and 6 reacted with dimethyl acetylene dicarboxylate at room temperature to give the complexes 15 and 16 which are formed by addition of the C≡C unit to the metal center and insertion into one of the metal‐selenium bonds. The proposed structures in solution were deduced from NMR data (¹H, ¹¹B, ¹³C, ⁷⁷Se, ¹⁰³Rh NMR), and an X‐ray structural analysis was carried out for the rhodium complex 12 .     

Bonding in Diborane–Metal Complexes: A Quantum‐Chemical and Experimental Study of Complexes Featuring Early and Late Transition Metals

The coordination chemistry of the doubly base‐stabilised diborane(4), [HB(hpp)]₂ (hpp=1,3,4,6,7,8‐hexahydro‐2H‐pyrimido‐[1,2‐a]pyrimidinate), was extended by the synthesis of new late transition‐metal complexes containing Cu^I and Rh^I fragments. A detailed experimental study was conducted and quantum‐chemical calculations on the metal–ligand bonding interactions for [HB(hpp)]₂ complexes of Group 6, 9, 11 and 12 metals revealed the dominant B? H? M interactions in the case of early transition‐metal fragments, whereas the B? B? M bonding prevails in the case of the late d‐block compounds. These findings support the experimental results as reflected by the IR and NMR spectroscopic parameters of the investigated compounds. DFT calculations on [MeB(hpp)]₂ and model reactions between [B₂H₄ ? 2NMe₃] and [Rh(μ‐Cl)(C₂H₄)₂] showed that the bicyclic guanidinate allows in principle for an oxidative addition of the B? B bond. However, the formation of σ‐complexes is thermodynamically favoured. The results point to the selective B? H or B? B bond‐activation of diborane compounds by complexation, depending on the chosen transition‐metal fragment.     

Formal synthesis of amphidinin B

An efficient, convergent, and highly stereoselective formal synthesis of amphidinin B (1) is reported herein. In Amphidinin B both C10–C21 (4) and C1–C9 (5) fragments were derived from geraniol 6 and mono-PMB ether of 1,4-butane diol 7 in 19 and 9 steps, respectively. The key steps involved in this synthesis are Sharpless asymmetric epoxidation, Evans aldol, Julia olefination, oxa-Michael, Keck allylation, Mannich reaction, Evans asymmetric alkylation, and Yamaguchi esterification.     

Nucleophilic addition of aromatic amide oximes to [2-B<Subscript>10</Subscript>H<Subscript>9</Subscript>NCC<Subscript>2</Subscript>H<Subscript>5</Subscript>]<Superscript>–</Superscript> anion

A series of closo-decaborate anions containing an O-iminoacylamide oxime fragment were synthesized by nucleophilic addition of aromatic amide oximes to 2-propionitrilium closo-decaborate anion. The isolated compounds were characterized by IR, ¹H, ¹³C–{¹H}, and ¹¹B–{¹H} NMR, and mass spectra. The structure of (Ph₄P)[2-B₁₀H₉NH=C(Et)ON=C(NH₂)C₆H₄Me-2] was determined by single-crystal X-ray analysis.     

Enantioselective synthesis of aurisides A and B, cytotoxic macrolide glycosides of marine origin

The enantioselective synthesis of aurisides A and B, macrolide glycosides of marine origin, was achieved by a convergent approach. The C1-C9 segment 4 was prepared from (R)-pantolactone, and the C10-C17 segment 14 was synthesized from (R)-glycidyl trityl ether. The Nozaki-Hiyama-Kishi reaction between 4 and 14 and subsequent reactions gave seco acid 10, which was converted into the aglycon (3) of aurisides by construction of the 14-membered lactone and bromine-substituted conjugated diene. The glycosylation reaction of the aglycon provided aurisides A and B.     

Influence of the Conditions for Preparing LaPO<Subscript>4</Subscript>-Based Materials with Inclusions of the LaP<Subscript>3</Subscript>O<Subscript>9</Subscript> Phase on Their Thermal and Mechanical Properties

A material based on lanthanum orthophosphate LaPO₄ with inclusion of particles of lanthanum metaphosphate LaP³O₉ was synthesized. The influence of the process parameters of the synthesis on the structure and properties of the material was determined. Heat treatment of the coprecipitated lanthanum phosphates at 700°C leads to the formation of a nanopowder with the LaPO₄crystallite size of approximately 17 nm. Heat treatment of the nanopowder at temperatures from 1100 to 1500°C yields compact materials based on the LaPO₄–LaP₃O₉ system. The heat treatment of the nanopowder at 1100°C leads to a sharp decrease in the porosity of the material (to ~5%) at insignificant grain growth (200–400 nm); under these conditions, the thermal conductivity [λ(25°C) = 3.2 W m–1 K^–1], microhardness [Hv(25°C) = 4.6 ± 0.4 GPa], Young’s modulus [E(25°C) = 132 ± 9 GPa], and cracking resistance [K_1c(25°C) = 1.6 ± 0.1 MPa m^1/2] pass through maxima. The thermal expansion coefficient of the material depends on the heat treatment conditions only slightly and amounts to (8.2 ± 0.2) × 10^–6 K^–1.     

Synthesis of 1‐silacyclopent‐2‐ene derivatives using 1,2‐hydroboration, 1,1‐organoboration and protodeborylation

The reaction of di(alkyn‐1‐yl)vinylsilanes R¹(H₂C═CH)Si(C≡C―R)₂ (R¹ = Me ( 1 ), Ph ( 2 ); R = Bu (a), Ph (b), Me₂HSi (c)) at 25°C with 1 equiv. of 9‐borabicyclo[3.3.1]nonane (9‐BBN) affords 1‐silacyclopent‐2‐ene derivatives ( 3a , 3b , 3c , 4a , 4b ), bearing one Si―C≡C―R function readily available for further transformations. These compounds are formed by consecutive 1,2‐hydroboration followed by intramolecular 1,1‐carboboration. Treated with a further equivalent of 9‐BBN in benzene they are converted at relatively high temperature (80–100°C) into 1‐alkenyl‐1‐silacyclopent‐2‐ene derivatives ( 5a , 5b 6a , 6b ) as a result of 1,2‐hydroboration of the Si―C≡C―R function. Protodeborylation of the 9‐BBN‐substituted 1‐silacyclopent‐2‐ene derivatives 3 , 4 , 5 , 6 , using acetic acid in excess, proceeds smoothly to give the novel 1‐silacyclopent‐2‐ene ( 7 , 8 , 9 , 10 ). The solution‐state structural assignment of all new compounds, i.e. di(alkyn‐1‐yl)vinylsilanes and 1‐silacyclopent‐2‐ene derivatives, was carried out using multinuclear magnetic resonance techniques (¹H, ¹³C, ¹¹B, ²⁹Si NMR). The gas phase structures of some examples were calculated and optimized by density functional theory methods (B3LYP/6‐311+G/(d,p) level of theory), and ²⁹Si NMR parameters were calculated (chemical shifts δ²⁹Si and coupling constants ⁿJ(²⁹Si,¹³C)). Copyright © 2014 John Wiley & Sons, Ltd.     

Stereoelectronic control of the retro diels–alder reaction in 8-(N-pyrrolidyl)bicyclo[4.3.0]nona-3,7-diene isomers

The cis- and trans-annulated isomers of 8-(N-pyrrolidyl)bicyclo[4.3.0]nona-3,7-diene show different propensities for the retro Diels–Alder fragmentation following electron impact ionization. Molecular ions of the cis-annulated isomer decompose predominantly via the retro Diels–Alder reaction to give [C₉H₁₃N] ⁺· fragments of the appearance energy (AE)=8.45±0.05eV and critical energy E_c=133±8kJ mol^?1. The trans-annulated isomer gives abundant [M–H]⁺ (AE=9.34±0.08eV) and [M–C₆H₆]⁺· fragments, in addition to [C₉H₁₃N]⁺· ions of AE=8.98±0.05eV and E_c=181±8kJ mol^?1. The ionization energies (IE) were determined as IE_cis=7.07±0.05 eV and IE_trans=7.10±0.06eV. The stereochemical information is much less pronounced in unimolecular decompositions of long-lived (metastable) molecular ions which show very similar fragmentation patterns for both geometrical isomers. Nevertheless, the isomers exhibit different kinetic energy release values in the retro Diels–Alder fragmentation; T_0.5=3.8±0.3 and 4.8±0.2 kJ mol^?1 for the cis and trans isomer respectively. Topological molecular orbital calculations indicate that the retro Diels–Alder reaction prefers a two-step path, with a subsequent cleavage of the C(5)? C(6) and C(1)? C(2) bonds. The open-ring distonic intermediate represents the absolute minimum on the reaction energy hypersurface. The cleavage of the C(1)? C(2) bond is the rate-determining step in the decomposition of the cis isomer, with the critical energy calculated as 137 kJ mol^?1. The cleavage of the C(5)? C(6) bond becomes the rate-determining step in the trans-annulated isomer because of stereoelectronic control. The difference in the energy barriers to this cleavage in the isomers (ΔE=95k Jmol^?1) provides a quantitative estimate of the magnitude of the stereoelectronic effect in cation radicals.     

Neusynthese des rinderinsulin-b-ketten-s-sulfonates

A novel synthesis of the bovine insulin B chain in the blocked form (7) applying N^im-Trt-, Cys-SEt-, N^G-H⊕- and Benzyl-protection in the residual positions is described starting from the partial fragments 1–4. By choice the deprotection is possible by HF, HBr/TFE with C₂H₅SH addition and also under special conditions by catalytic hydrogenolysis. HBr/TFE acidolysis and hydrogenolysis lead to the best resultates in respect to yield and homogeneity of the final product. Thus Bunte salts are received in good yield related to the protected B chain and with the same insulin forming potency as such of native provenience.     

Synthesis,Structure, and Magnetic Properties of Three Novel Sandwich‐type Tungstobismuthates with Triethanolamine

Three novel sandwich‐type polyoxotungstates ( 1 – 3 ) were synthesized in good yield using an in‐situ conventional solution synthesis method by reaction in aqueous media below 80 °C. Compounds 1 – 3 represent the first structurally characterized β‐B‐BiW₉ sandwich‐type polyoxometalates with triethanolamine cations. All three compounds have the same building unit [(X(H₂O)₃)₂(X_0.5W_0.5O)₂(β‐B‐BiW₉O₃₃)₂)]^10– [X = Mn^II ( 1 ), Co^II ( 2 ), Ni^II ( 3 )]. The adjacent units of 1 or 2 are joined by Na⁺ cations in different ways to construct 1D chains or 2D sheets. A 3D supramolecular structure is further formed by hydrogen bond interactions among water molecules and protonated triethanolamine cations. Meanwhile only compound 3 shows a 0D structure. The compounds were characterized by elemental analysis, IR spectroscopy, TG analysis, and single‐crystal X‐ray diffraction. Magnetic measurements on a sample of 1 show the presence of paramagnetic interactions.     

Aglycon-Disaccharide Coupling in Mithramycin Analog Synthesis

ABSTRACT

Mithramycin (1), chromomycin A₃, and olivomycin A are structurally related, antitumor agents which belong to the aureolic acid family of antibiotics.¹ Considerable research on the synthesis of both the aglycon^2-4 and carbohydrate^7-9 portions of these molecules naturally has led to interest in methods for joining carbohydrate and aglycon units together.¹⁰ One type of coupling which is required for aureolic acid synthesis is that of the A-B disaccharide to the phenolic hydroxyl group at C-6.¹¹ In this communication such a process is described along with a flexible procedure for the formation of the protected A-B disaccharide used in the coupling process.     

C–C bridged Ni(II) complexes bearing β‐keto‐9‐fluorenyliminato ligands prepared by different in situ bonding mechanisms and their use in catalytic (co)polymerization of norbornene and styrene

Two C–C bridged Ni(II) complexes bearing β‐keto‐9‐fluorenyliminato ligands with electron‐withdrawing groups (─CF₃), Ni{PhC(O)CHC[N(9‐fluorenyl)]CF₂}₂ (Ni 1 ) and Ni{CF₃C(O)CHC[N(9‐fluorenyl)]Ph}₂ (Ni 2 ), were synthesized by metal coordination reaction and different in situ bonding mechanisms. The C–C bridged bonds of Ni 1 were formed by in situ intramolecular trifluoromethyl and 9‐fluorenyl carbon–carbon cross‐coupling reaction and those of Ni 2 were formed by in situ intramolecular 9‐fluorenyl carbon–carbon radical coupling reaction mechanism. The obtained complexes were characterized using ¹H NMR spectroscopy and elemental analyses. The crystal and molecular structures of Ni 1 and Ni 2 with C–C bridged configuration were determined using X‐ray diffraction. Ni 1 and Ni 2 were used as catalysts for norbornene (NB) polymerization after activation with B(C₆F₅)₃ and the catalytic activities reached 10⁶ g_polymer mol_Ni^?1 h^?1. The copolymerization of NB and styrene catalyzed by the Ni 1 /B(C₆F₅)₃ system showed high activity (10⁵ g_polymer mol_Ni^?1 h^?1) and the catalytic activities decreased with increasing feed content of styrene. All vinyl‐type copolymers exhibited high molecular weight (10⁴ g mol^?1), narrow molecular weight distribution (M_w/M_n = 1.71–2.80), high styrene insertion ratios (11.13–50.81%) and high thermal stability (T_d > 380°C) and could be made into thin films with high transparency in the visible region (400–800 nm).     

Total Synthesis of Δ12‐Prostaglandin J3: Evolution of Synthetic Strategies to a Streamlined Process

The total synthesis of Δ¹²‐prostaglandin J₃ (Δ¹²‐PGJ₃, 1 ), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross‐conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14 , whose lone stereocenters were generated by an asymmetric Tsuji–Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent‐governed regioselectivity pattern for the Rh‐catalyzed C?H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14 , exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57 , and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large‐scale production of Δ¹²‐PGJ₃ and designed analogues for further biological and pharmacological studies.     

Hemilability of 2-(1H-imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine ligands: Imidazole and oxazole ring Lewis basicity,Ni(II)/Pd(II) complex structures and spectra

Fourteen new organic molecules A1–A4, B1–B5, C1–C4 and D and a series of transition metal(II) complexes (Ni1–Ni9 and Pd1–Pd2b) were synthesized and studied in order to characterize the hemilability of 2-(1H-imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine ligands (A1–A4 = 2-R²-6-(4,5-diphenyl-1R¹-imidazol-2-yl)pyridines, R¹ = H or CH₃, R² = H or CH₃; B1–B5 = 1-R²-2-(pyridin-2-yl)-1R¹-phenanthro[9,10-d]imidazoles/oxazoles, R¹ = H or CH₃, R² = H or CH₃; C1–C4 = 2-(6-R²-pyridin-2-yl)-1H-imidazo/oxazo[4,5-f][1,10]phenanthrolines, R² = H or CH₃; D = 2-mesityl-1H-imidazo[4,5-f][1,10]phenanthroline). They were also used to study the substituent effects on the donor strengths as well as the coordination chemistries of the imidazole/oxazole fragments of the hemilabile ligands.All the observed protonation–deprotonation processes found within pH 1–14 media pertain to the imidazole or oxazole rings rather than the pyridyl Lewis bases. The donor characteristics of the imidazole/oxazole ring can be estimated by spectroscopic methods regardless of the presence of other strong N donor fragments. The oxazoles possessed notably lower donor strengths than the imidazoles. The electron-withdrawing influence and capacity to hinder the azole base donor strength of 4,5-azole substituents were found to be in the order phenanthrenyl (B series) > 4,5-diphenyl (A series) > phenanthrolinyl (C series). An X-ray structure of Ni5b gave evidence for solvent induced ligand reconstitution while the structure of Pd2b provided evidence for solvent induced metal–ligand bond disconnection.Interestingly, alkylation of 1H-imidazoles did not necessarily produce the anticipated push of electron density to the donor nitrogen. Furthermore, substituents on the 4,5-carbons of the azole ring were more important for tuning donor strength of the azole base. DFT calculations were employed to investigate the observed trends. It is believed that the information provided on substituent effects and trends in this family of ligands will be useful in the rational design and synthesis of desired azole-containing chelate ligands, tuning of donor properties and application of this family of ligands in inorganic architectural designs, template-directed coordination polymer preparations, mixed-ligand inorganic self-assemblies, etc.