Two‐dimensional liquid chromatography analysis of all‐trans‐, 9‐cis‐, and 13‐cis‐astaxanthin in raw extracts from Phaffia rhodozyma

An effective two‐dimensional liquid chromatography method has been established for the analysis of all‐trans‐astaxanthin and its geometric isomers from Phaffia rhodozyma employing a C18 column at the first dimension and a C30 column in the second dimension, connected by a 10‐port valve using the photo‐diode array detector. The regression equation of astaxanthin calibration curve was established, and the precision and accuracy values were found to be in the range of 0.32–1.14% and 98.21–106.13%, respectively. By using two‐dimensional liquid chromatography, it was found that day light, ultrasonic treatment, and heat treatment have significant influence on the content of all‐trans‐astaxanthin in the extract from P. rhodozyma due to the transformation of all‐trans‐astaxanthin to cis‐astaxanthin. The day light and ultrasonic treatments more likely transform all‐trans‐astaxanthin to 9‐cis‐astaxanthin, and the thermal treatment transforms all‐trans‐astaxanthin to 13‐cis‐astaxanthin. These results indicate that the two‐dimensional liquid chromatography method can facilitate monitoring astaxanthin isomerization in the raw extract from P. rhodozyma. In addition, the study will provide a general reference for monitoring other medicals and bioactive chemicals with geometric isomers.     

Structure‐Dependent cis/trans Isomerization of Tetraphenylethene Derivatives: Consequences for Aggregation‐Induced Emission

The isomerization and optical properties of the cis and trans isomers of tetraphenylethene (TPE) derivatives with aggregation‐induced emission (AIEgens) have been sparsely explored. We have now observed the tautomerization‐induced isomerization of a hydroxy‐substituted derivative, TPETH‐OH, under acidic but not under basic conditions. Replacing the proton of the hydroxy group in TPETH‐OH with an alkyl group leads to the formation of TPETH‐MAL, for which the pure cis and trans isomers were obtained and characterized by HPLC analysis and NMR spectroscopy. Importantly, cis‐TPETH‐MAL emits yellow fluorescence in DMSO at ?20 °C whereas trans‐TPETH‐MAL shows red fluorescence under the same conditions. Moreover, the geometry of cis‐ and trans‐TPETH‐MAL remains unchanged when they undergo thiol–ene reactions to form cis‐ and trans‐TPETH‐cRGD, respectively. Collectively, our findings improve our fundamental understanding of the cis/trans isomerization and photophysical properties of TPE derivatives, which will guide further AIEgen design for various applications.     

Novel Synthesis of 2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones and Their S‐Oxides

2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones 1a – e were synthesized by cyclocondensation of 2‐(thiocyanato)cyclohexene‐1‐carboxanilides 9 as a convenient new method. Their S‐oxides 10 were prepared by two routes, either by oxidation of 1 or dehydration of rac‐cis‐3‐hydroperoxysultims 11 . Furthermore, compounds 1 have been identified by HPLC? API‐MS‐MS as intermediates in the oxidation process of the salts 6 . The hydroperoxides 12b and rac‐trans‐ 11b have been unambiguously detected by HPLC? MS investigations and in the reaction of rac‐cis‐ 13b with H₂O₂ to the hydroperoxides rac‐trans‐ 11b and rac‐cis‐ 11b .     

Ring opening of pyridines: the pseudo‐cis and pseudo‐trans isomers of tetra‐n‐butylammonium 4‐nitro‐5‐oxo‐2‐pentenenitrilate

The reaction of 2‐chloro‐5‐nitropyridine with two equivalents of base produces the title carbanion as an intermediate in a ring‐opening/ring‐closing reaction. The crystal structures of the tetra‐n‐butylammonium salts of the intermediates, C₁₆H₃₆N⁺·C₅H₃N₂O₃⁻, revealed that pseudo‐cis and pseudo‐trans isomers are possible. One crystal structure displayed a mixture of the two isomers with approximately 90% pseudo‐cis geometry and confirms the structure predicted by the S_N(ANRORC) mechanism. The pseudo‐cis intermediate undergoes a slow isomerization over a period of months to the pseudo‐trans isomer, which does not have the appropriate geometry for the subsequent ring‐closing reaction. The structure of the pure pseudo‐trans isomer is also reported. In both isomers, the negative charge is highly delocalized, but relatively small differences in C—C bond distances indicate a system of conjugated double bonds with the nitro group bearing the negative charge. The packing of the two unit cells is very similar and largely determined by the interactions between the planar carbanion and the bulky tetrahedral cation.     

Iodine‐Catalyzed Highly Diastereoselective Synthesis of trans‐2,6‐Disubstituted‐3,4‐Dihydropyrans: Application to Concise Construction of C28–C37 Bicyclic Core of (+)‐Sorangicin A

A novel iodine‐catalyzed highly diastereoselective synthesis of trans‐2,6‐disubstituted‐3,4‐dihydropyrans have been achieved from δ‐hydroxy α,β‐unsaturated aldehydes by treating with allyltrimethyl silane in THF at room temperature with good to excellent yields. This methodology has been successfully implemented for a concise asymmetric synthesis of C28–C37 dioxabicyclo[3.2.1]octane ring system of (+)‐sorangicin A in 8 steps with 21 % overall yield.     

Structural characterization of isomeric 2,3,5‐substituted tetrahydropyrrolo[3,4‐d]isoxazole‐4,6‐diones prepared by cycloaddition of N‐methyl‐C‐arylnitrones to N‐phenyl‐ or N‐methylmaleimide

1,3‐Dipolar cycloaddition reactions of N‐methyl‐C‐arylnitrones with N‐phenyl‐ or N‐methylmaleimide were studied. The reaction of p‐dimethylamino‐, 4‐benzyloxy‐3‐methoxy‐, p‐nitro‐ and p‐chloro‐substituted phenylnitrones with N‐phenylmaleimide gave cis and trans cycloadducts but that of the corresponding phenylnitrones with N‐methylmaleimides only the cis adducts in the case of p‐dimethylamino and 4‐benzyloxy‐3‐methoxy substitution. All cis adducts attain a biased conformation whereas the trans forms are shown (by ¹H NMR at 233 K and ¹³C NMR at 208 K) to be mixtures of two invertomers, namely o‐(N‐lone pair antiperiplanar to 3H; minor) and i‐conformations (3H‐C‐C‐3aH dihedral angle close to 90°; major). PM3 and DFT calculations at the B3LYP/6–31G(d) level of theory prove qualitatively that these two conformers of the trans adduct are of comparable stability and represent energy minima.     

Acyclic Palladium(II)‐N‐heterocyclic Carbene Metallacrown Ether Complexes: Synthesis,Structure and Catalytic Activity

Novel acyclic Pd(II)‐N‐heterocyclic carbene (NHC) metallacrown ethers 5a , 5b have been synthesized. Reaction of the imidazolium salts bearing a long polyether chain with Ag₂O afforded Ag‐NHC complexes, which then reacted as carbene transfer agent with PdCl₂(MeCN)₂ to give the desired acyclic Pd(II)‐NHC metallacrown ether complexes 5a and 5b . The ¹H NMR and ¹³C NMR spectra show 5a and 5b exist as mixtures of cis and trans isomers in solution. The trans isomer of 5a was characterized by X‐ray diffraction, which clearly demonstrated two pseudo‐crown ether cavities in trans‐ 5a . Pd(II)‐NHC complexes 5a and 5b have been shown to be highly effective in the Suzuki‐Miyaura reactions of a variety of aryl bromides in neat water without the need of inert gas protection.     

Crosslinking network of bio‐based bis‐functional epoxides derived from trans‐limonene oxide

The thiol‐ene reaction between trans‐limonene oxide (trans‐LO) and ethane‐1,2‐dithiol in the presence of triethylborane affords a bio‐based bis‐functional epoxide (bis‐trans‐LO). The crosslinking reaction of bis‐trans‐LO with branched polyethyleneimine (BPEI; M_n = 600; BPEI₆₀₀) at a feed ratio of bis‐trans‐LO/BPEI₆₀₀ = 57/43 (wt/wt) yields the corresponding network polymer with T_d10 (10% thermal decomposition temperature) of 304.7 °C in 98% yield. In contrast, negligible amounts of network polymer are obtained by the reaction of bis‐LO (bis‐functional epoxide derived from cis and trans‐LO) and BPEI₆₀₀ regardless of the feed ratio. The mechanical strengths as measured by direct tensile tests of the network polymers derived from bis‐trans‐LO and BPEI_600,1800 (M_n = 600 and 1800) were approximately 16 and 11 times higher than that of bis‐LO and BPEI₁₈₀₀, respectively. The tensile shear strengths of the metal‐to‐metal adhesive bonds induced by bis‐trans‐LO and BPEI_600,1800 were 9.5 and 14.1 MPa, respectively. DMA revealed that the storage modulus of the network polymer derived from bis‐trans‐LO and BPEI₁₈₀₀ in the rubber region was higher than that of the material prepared from bis‐LO and BPEI₁₈₀₀, indicating higher crosslink density of the bis‐trans‐LO/BPEI₁₈₀₀ system. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2466–2473     

trans‐Chloridobis[(Z)‐1‐imino‐1‐methoxyethane‐κN](triphenylphosphane‐κP)platinum(II) chloride monohydrate

The title compound, [PtCl(C₃H₇NO)₂(C₁₈H₁₅P)]Cl·H₂O or trans‐[PtCl{Z‐HN=C(Me)OMe}₂(PPh₃)]Cl·H₂O, crystallizes from an acetone solution of isomeric trans‐[PtCl{E‐HN=C(Me)OMe}₂(PPh₃)]Cl. The two HN=C(Me)OMe ligands show typical π‐bond delocalization over the N—C—O group [Cini, Caputo, Intini & Natile (1995). Inorg. Chem. 34 , 1130–1137] and have the unprecedented Z–anti configuration. The relative orientation of the imino ether ligands is head‐to‐tail.     

Uranium–Carbene–Imido Metalla‐Allenes: Ancillary‐Ligand‐Controlled cis‐/trans‐Isomerisation and Assessment of trans Influence in the R2C=UIV=NR′ Unit (R=Ph2PNSiMe3; R′=CPh3)

Uranium(IV)–carbene–imido complexes [U(BIPM^TMS)(NCPh₃)(κ²‐N,N′‐BIPY)] ( 2 ; BIPM^TMS=C(PPh₂NSiMe₃)₂; BIPY=2,2‐bipyridine) and [U(BIPM^TMS)(NCPh₃)(DMAP)₂] ( 3 ; DMAP=4‐dimethylamino‐pyridine) that contain unprecedented, discrete R₂C=U=NR′ units are reported. These complexes complete the family of E=U=E (E=CR₂, NR, O) metalla‐allenes with feasible first‐row hetero‐element combinations. Intriguingly, 2 and 3 contain cis‐ and trans‐C=U=N units, respectively, representing rare examples of controllable cis/trans isomerisation in f‐block chemistry. This work reveals a clear‐cut example of the trans influence in a mid‐valent uranium system, and thus a strong preference for the cis isomer, which is computed in a co‐ligand‐free truncated model—to isolate the electronic trans influence from steric contributions—to be more stable than the trans isomer by approximately 12 kJ mol^?1 with an isomerisation barrier of approximately 14 kJ mol^?1.     

Two trans‐4‐aminoazoxybenzenes

Two isomeric trans‐4‐amino­azoxy­benzenes, trans‐1‐(4‐amino­phenyl)‐2‐phenyl­diazene 2‐oxide (α, C₁₂H₁₁N₃O) and trans‐2‐(4‐amino­phenyl)‐1‐phenyl­diazene 2‐oxide (β, C₁₂H₁₁N₃O), have been characterized by X‐ray diffraction. The α isomer is almost planar, having torsion angles along the C_aryl—N bonds of only 4.9 (2) and 8.0 (2)°. The relatively short C_aryl—N bond to the non‐oxidized site of the azoxy group [1.401 (2) Å], together with the significant quinoid deformation of the respective phenyl ring, is evidence of conjugation between the aromatic sextet and the π‐electron system of the azoxy group. The geometry of the β isomer is different. The non‐substituted phenyl ring is twisted with respect to the NNO plane by ca 50°, whereas the substituted ring is almost coplanar with the NNO plane. The non‐oxidized N atom in the β isomer has increased sp³ character, which leads to a decrease in the N—N—C bond angle to 116.8 (2)°, in contrast with 120.9 (1)° for the α isomer. The deformation of the C—C—C angles (1–2°) in the phenyl rings at the substitution positions is evidence of the different character of the oxidized and non‐oxidized N atoms of the azoxy group. In the crystal structures, mol­ecules of both isomers are arranged in chains connected by weak N—H?O (α and β) and N—H?N (β) hydrogen bonds.     

Formal Total Synthesis of Fostriecin by 1,4‐Asymmetric Induction with an Alkyne–Cobalt Complex

The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. The synthetic challenges were the construction of four stereogenic centers and the conformationally labile cis‐cis‐trans‐triene moiety. Previous total syntheses have employed at least two asymmetric reactions that required the use of an external chiral auxiliary. Although remote stereoinduction in a 1,4‐relationship is considered difficult, we have developed a notable 1,4‐asymmetric induction that utilizes an alkyne–cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3‐asymmetric induction with a higher‐order alkynyl‐zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this route. The labile cis‐cis‐trans‐triene unit was constructed at a late stage of the synthesis by diastereoselective coupling of a dienyne and an aldehyde unit, followed by reduction.     

cis‐trans Peptide‐Bond Isomerization in α‐Methylproline Derivatives

α‐Methyl‐L ‐proline is an α‐substituted analog of proline that has been previously employed to constrain prolyl peptide bonds in a trans conformation. Here, we revisit the cis‐trans prolyl peptide bond equilibrium in derivatives of α‐methyl‐L ‐proline, such as N‐Boc‐protected α‐methyl‐L ‐proline and the hexapeptide H‐Ala‐Tyr‐αMePro‐Tyr‐Asp‐Val‐OH. In Boc‐α‐methyl‐L ‐proline, we found that both cis and trans conformers were populated, whereas, in the short peptide, only the trans conformer was detected. The energy barrier for the cis‐trans isomerization in Boc‐α‐methyl‐L ‐proline was determined by line‐shape analysis of NMR spectra obtained at different temperatures and found to be 1.24 kcal/mol (at 298 K) higher than the corresponding value for Boc‐L ‐proline. These findings further illuminate the conformationally constraining properties of α‐methyl‐L ‐proline.     

Hydrogallierungsreaktionen mit den Monoalkinen H5C6‐C≡C‐SiMe3 und H5C6‐C≡C‐CMe3 – cis/trans‐Isomerie und Substituentenaustausch

Hydrogallation Reactions Involving the Monoalkynes H₅C₆‐C≡C‐SiMe₃ and H₅C₆‐C≡C‐CMe₃ – cis/trans Isomerisation and Substituent Exchange Phenyl‐trimethylsilylethyne, H₅C₆‐C≡C‐SiMe₃, reacted with different dialkylgallium hydrides, R₂Ga‐H (R = Me, Et, nPr, iPr, tBu), by the addition of one Ga‐H bond to its C≡C triple bond (hydrogallation). The gallium atoms attacked selectively those carbon atoms, which were also attached to trimethylsilyl groups. The cis arrangement of Ga and H across the resulting C=C double bonds resulted only for the sterically most shielded di(tert‐butyl)gallium derivative, while in all other cases spontaneous cis/trans rearrangement occurred with the quantitative formation of the trans addition products. The diethyl compound Et₂Ga‐C(SiMe₃)=C(H)‐C₆H₅ ( 2 ) gave by substituent exchange the secondary products EtGa[C(SiMe₃)=C(H)‐C₆H₅]₂ ( 7 , Z,Z) and Ga[C(SiMe₃)=C(H)‐C₆H₅]₃ ( 8 ). Interestingly, compound 8 has two alkenyl groups with a Z configuration, while the third C=C double bond has the cis arrangement of Ga and H (E configuration). The reversibility of the cis/trans isomerisation of hydrogallation products was observed for the first time. tert‐Butyl‐phenylethyne gave the simple addition product, R₂Ga(C₆H₅)=C(H)‐CMe₃ ( 9 ), only with di(n‐propyl)gallium hydride.     

Unexpected Formation of Dimethylthioketene Cycloadducts in the Reaction of 1,3‐Diphenylaziridine‐2,2‐dicarboxylate with Cyclobutanethione Derivatives

The reaction of 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 1 ) with cis‐1‐alkyl‐2,3‐diphenylaziridines 5 in boiling toluene yielded the expected trans‐configured spirocyclic 1,3‐thiazolidines 6 (Scheme 1). Analogously, dimethyl trans‐1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (trans‐ 7 ) reacted with 1 and the corresponding dithione 2 , respectively, to give spirocyclic 1,3‐thiazolidine‐2,4‐dicarboxylates 8 (Scheme 2). However, mixtures of cis‐ and trans‐derivatives were obtained in these cases. Unexpectedly, the reaction of 1 with dimethyl 1,3‐diphenylaziridine‐2,2‐dicarboxylate ( 11 ) led to a mixture of the cycloadduct 13 and 5‐(isopropylidene)‐4‐phenyl‐1,3‐thiazolidine‐2,2‐dicarboxylate ( 14 ), a formal cycloadduct of azomethine ylide 12 with dimethylthioketene (Scheme 3). The regioisomeric adduct 16 was obtained from the reaction between 2 and 11 . The structures of 6b , cis‐ 8a , cis‐ 8b, 10 , and 16 have been established by X‐ray crystallography.     

Conformation‐Determined Through‐Bond versus Through‐Space Electronic Communication in Mixed‐Valence Systems with a Cross‐Conjugated Urea Bridge

Bis‐triarylamine 2 and cyclometalated diruthenium 6 (PF₆)₂ with a linear trans,trans‐urea bridge have been prepared, together with the bis‐triarylamine 3 and cyclometalated diruthenium 8 (PF₆)₂ with a folded cis,cis‐N,N‐dimethylurea bridge. The linear or folded conformations of these molecules are supported by single‐crystal X‐ray structures of 2 , 3 , and other related compounds. These compounds display two consecutive anodic redox waves (N ^{. +/0} or Ru^III/II processes) with a potential separation of 110–170 mV. This suggests that an efficient electronic coupling is present between two redox termini through the cross‐conjugated urea bridge. The degree of electronic coupling has been investigated by using spectroelectrochemical measurements. Distinct intervalence charge‐transfer (IVCT) transitions have been observed for mixed‐valent (MV) compounds with a linear conformation. The IVCT transitions can also be identified for the folded MV compounds, albeit with a much weaker intensity. DFT results support that the electronic communication occurs by a through‐bond and through‐space pathway for the linear and folded compounds, respectively. The IVCT transitions of the MV compounds have been reproduced by TDDFT calculations. For the purpose of comparison, a bistriarylamine and a diruthenium complex with an imidazolidin‐2‐one bridge and a urea‐containing mono‐triarylamine and monoruthenium complex have been synthesized and studied.     

trans‐4‐Bromo‐ONN‐azoxy­benzene at 100 K

The crystal structure of the α isomer of trans‐4‐bromo­azoxy­benzene [systematic name: trans‐1‐(bromophenyl)‐2‐phenyl­diazene 2‐oxide], C₁₂H₉BrN₂O, has been determined by X‐ray dif­frac­tion. The geometries of the two mol­ecules in the asymmetric unit are slightly different and are within ∼0.02 Å for bond lengths, ∼2° for angles and ∼3° for torsion angles. The azoxy bridges in both mol­ecules have the typical geometry observed for trans‐azoxy­benzenes. The crystal network contains two types of planar mol­ecules arranged in columns. The torsion angles along the Ar—N bonds are only 7 (2)°, on either side of the azoxy group.     

2,3,3a,4,9,9a‐Hexahydro‐9‐phenylbenzo[f]indene derivatives

The title compounds, 3a,9a‐trans‐9,9a‐trans‐4,4‐di­methyl‐9‐phenyl‐2,3,3a,4,9,9a‐hexa­hydro­benzo­[f]­indene, C₂₁H₂₄, (I), and 3a,4‐trans‐3a,9a‐cis‐9,9a‐trans‐4‐methoxy‐9‐phenyl‐2,3,3a,4,9,9a‐hexa­hydro­benzo­[f]­indene, C₂₀H₂₂O, (II), are products of the photoinduced electron‐transfer reaction of 1,1‐di­phenyl‐1,n‐alka­dienes. The molecular structures are in good agreement with those proposed from the reaction mechanisms. The central rings of the fused systems of both compounds take chair and boat conformations in (I) and (II), respectively. There are no remarkable short contacts shorter than the sum of the van der Waals radii in the crystals, but some weak C—H?π interactions are found.     

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).