Supramolecular structure of self-assembled synthetic zinc-13(1)-oxo-chlorins possessing a primary, secondary or tertiary alcoholic 3(1)-hydroxyl group: visible spectroscopic and molecular modeling studies

Zinc-chlorin 3 (see Fig. 2 in text) possessing a tertiary 3(1)-hydroxyl group and a 13-keto group was synthesized as a model for the antenna chlorophylls of green bacteria. Self-aggregation of 3 in nonpolar organic media was examined and compared to 1 and 2 possessing a primary and secondary 3(1)-hydroxyl group, respectively. Zinc-chlorin 3 self-aggregated in 1 vol% CH2Cl2-hexane to form oligomers and showed a red-shifted Qy maximum at 704 nm compared to the monomer (648 nm in CH2Cl2). This red-shift is larger than that of 2S (648-->697 nm) and comparable to that of 2R (648-->705 nm), but smaller than that of 1 (648-->740 nm), indicating that while a single 3(1)-methyl group (prim-OH-->sec-OH) suppressed close and/or higher aggregation, the additional 3(1)-methyl group (sec-OH-->tert-OH) did not further suppress aggregation. The relative stability of the aggregates was in the order 1 > 2R-3 > 2S as determined by visible spectral analyses. Molecular modeling calculations on dodecamers of zinc-chlorins 1, 2R and 3 gave similar well-ordered energy-minimized structures, while 1 stacked more tightly than 2R and 3. In contrast, 2S gave a relatively disordered (twisted) structure. The calculated dodecameric structures could explain the visible spectral data of 1-3 in nonpolar organic media.     

(2S,4S)-苯甲基-2-(6-氟-1H-吲哚-3-羰基)-4-羟基-吡咯烷-1-羧酸酯的合成

以4-羟基-L-脯氨酸为原料,经Cbz保护、偶联、Mitsunobu反应和水解合成了抗肿瘤新药Birinapant的重要中间体--(2S,4S)-苯甲基-2-(6-氟-1H-吲哚-3-羰基)-4-羟基吡咯烷-1-羧酸酯,总收率83%,其结构经¹H NMR和ESI-MS确证。     

Na2S-Mediated One-Pot Selective Deoxygenation of α-Hydroxyl Carbonyl Compounds including Natural Products

A practical method for the deoxygenation of α-hydroxyl carbonyl compounds under mild reaction conditions is reported here. The use of cheap and easy-to-handle Na₂S·9H₂O as the reductant in the presence of PPh₃ and N-chlorosuccinimide (NCS) enables the selective dehydroxylation of α-hydroxyl carbonyl compounds, including ketones, esters, amides, imides and nitrile groups. The synthetic utility is demonstrated by the late-stage deoxygenation of bioactive molecule and complex natural products.     

Lead Tetraacetate Cleavage of Chiral Phenylglycinol Derived Secondary Amines Without Racemization

Diastereomerically enriched N-(1,1-disubstituted methyl)(2 ‘-hydroxyl’-phenylethyl) amines were oxidatively converted to enantiomerically enriched primary disubstituted methylamines in excellent yields without racemization, using an improved lead tetraacerate (LTA) procedure.     

A Per-O-Isoprofylidene Derivative of (1→4)-β-D-Mannan

Abstract

Isopropylidene acetals of carbohydrates are important as intermediates for the synthesis of other sugar derivatives. The isopropylidenation reaction is generally applied to only low molecular weight carbohydrates. However in 1982, we applied the reaction to a polysaccharide² and demonstrated that (1→3)-β-D-glucan was isopropylidenated at the 4- and 6-hydroxyl groups of the D-glucose units. These results suggested that some chemical modification at the unprotected 2-hydroxyl groups might be possible. Consequently, (1→3)-β-D-glucomannan^3,4 was derived from (1→3)-β-D-glucan through inversion of the 2-hydroxyl groups.     

Urinary metabolites of cinobufagin in rats and their antiproliferative activities

Cinobufagin was one of the important cardenolidal steroids and a major component of Chan'Su, a famous traditional Chinese medicine. The urinary metabolites of cinobufagin after single oral doses of 25?mg?kg?1 in rats were investigated. Eleven metabolites were isolated and purified by liquid-liquid extraction, open-column chromatography, medium-pressure liquid chromatography, as well as semi-preparative high-performance liquid chromatography. Their structures were elucidated by chemical and various spectroscopic methods, which were identified as desacetylcinobufagin (M-1), 3-oxo-desacetylcinobufagin (M-2), 3-oxo-cinobufagin (M-3), 3-epi-desacetylcinobufagin (M-4), 3-epi-12β-hydroxyl desacetylcinobufagin (M-5), 5β-hydroxyl cinobufagin (M-6), 5β-hydroxyl desacetylcinobufagin (M-7), 12β-hydroxyl cinobufagin (M-8), 1β,12β-dihydroxyl cinobufagin (M-9), 12β-hydroxyl desacetylcinobufagin (M-10) and 1β,12β-dihydroxyl desacetylcinobufagin (M-11), respectively. Among them, M-1 was the main urinary metabolite of cinobufagin with a yield of 17.7%. Most metabolites were hydroxylated products of cinobufagin at C-1β, 5β and 12β positions, as well as deacetylated products at C-16. Except M-1, M-4 and M-7, the other eight metabolites were novel in vivo metabolites of cinobufagin. Some metabolites showed potential cytotoxicity against human hepatoma cells (HepG2) and human leukaemia (K562, HL-60) cells; however, their cytotoxicities generally decreased after metabolic conversion.     

Acid-catalyzed dehydration of naphthalene-cis-1,2-dihydrodiols: origin of impaired resonance effect of 3-substituents

Acid-catalyzed dehydrations of substituted naphthalene-cis-1,2-dihydrodiols occur with loss of the 1- or 2-OH group to form 2- and 1-naphthols, respectively. Effects of substituents MeO, Me, H, F, Br, I, and CN at 3-, 6-, and 7-positions of the naphthalene ring are consistent with rate-determining formation of β-hydroxynaphthalenium ion (carbocation) intermediates. For reaction of the 1-hydroxyl group the 3-substituents are correlated by the Yukawa-Tsuno relationship with ρ = -4.7 and r = 0.25 or by σ(p) constants with ρ = -4.25; for reaction of the 2-hydroxyl group the 3-substituents are correlated by σ(m) constants with ρ = -8.1. The correlations for the 1-hydroxyl imply a surprisingly weak resonance interaction of +M substituents (MeO, Me) with a carbocation reaction center but are consistent with the corresponding correlation for acid-catalyzed dehydration of 3-substituted benzene-cis-1,2-dihydrodiols for which ρ = -6.9 and r = 0.43. Substituents at the 6- and 7-positions of the naphthalene rings by contrast are correlated by σ(+) with ρ = -3.2 for reaction of the 1-hydroxyl group and ρ = -2.7 for reaction of the 2-hydroxyl group. The unimpaired resonance implied by these substituent effects appears to be inconsistent with a previous explanation of the weak resonance of the 3-substituents in terms of imbalance of charge development and/or nonplanarity of the benzenium ring in the transition state. An alternative possibility is that the adjacent hydroxyl group interferes sterically with conjugation of +M substituents. "Hyperaromaticity" of the arenium ion intermediates does not appear to be a factor influencing this behavior.     

Syntheses of 2-acetyl-3-hydroxy-1-n-propylpyrrole from isomaltol and 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones from maltol

2-Acetyl-3-hydroxyfuran (2) reacts with n-propylamine affording 2-acetyl-3-hydroxy-1-n-propylpyrrole (3) in 63% yield. The transformation of 2-methyl-3-hydroxy-4-pyrone (4) into 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones is achieved by benzylation of the 3-hydroxyl group whereupon the product reacts with ammonia and the corresponding pyridone is obtained. The pyridone is alkylated with alkyl bromides and after hydrobromic acid in acetic acid cleavage of the 3-position ether function, 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones are obtained in 48% overall yield.     

Cytotoxic polyketides containing tetramic acid moieties isolated from the fungus Myceliophthora Thermophila: elucidation of the relationship between cytotoxicity and stereoconfiguration

Five new polyketides that contain tetramic acids, myceliothermophins A-E, were isolated from the thermophilic fungus Myceliophthora thermophila. Two sets of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one diastereomers, myceliothermophins A/B and C/D, were separated as pure compounds by using silica-gel column chromatography and recycling reverse-phase high-performance liquid chromatography (RP-HPLC). The relative configurations of the chiral centers in 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties were deduced from NOESY correlations. In the cytotoxic assay, the 5-(2-methylpropyldiene)-1H-pyrrol-2(5H)-one analogue (myceliothermophin E) exhibited inhibition against four cancer cell lines. In addition, the significant inhibitory effect of myceliothermophins A and C and the inactivity of myceliothermophins B and D revealed the importance of the relative configurations of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties on their cytotoxicity potency against cancer cells.     

^1^3C NMR研究稀土柠檬酸配合物的溶液配位结构

用稀土离子诱导位移和顺磁弛豫时间测定等NMR方法研究了稀土柠檬酸配合物在pH 7.4的溶液中的配位结构。结果表明稀土离子通过3-羟基和3-羧基与柠檬酸配体形成1:2的配合物, 两个端羧基没有参与配位。通过计算稀土离子和柠檬酸配体中各个碳原子间的空间距离的相对比, 建立了稀土离子与柠檬酸配体配位的新模式。     

Salen-based chiral fluorescence polymer sensor for enantioselective recognition of α-hydroxyl carboxylic acids

(R,R)-Salen-based chiral polymer P-1 was synthesized by the polymerization of 5,5'-((2,5-dibutoxy-1,4-phenylene)bis(ethyne-2,1-diyl))bis(2-hydroxy-3-(piperidin-1-ylmethyl) benzaldehyde (M-1) with (1R,2R)-cyclohexane-1,2-diamine (M-2) via nucleophilic addition- elimination reaction, and (R,R)-salan-based polymer P-2 could be obtained by the reduction reaction of P-1 with NaBH(4). (R,R)-Salen-based chiral polymer P-1 can exhibit greater fluorescence enhancement response toward (l)-α-hydroxyl carboxylic acids, and the value of enantiomeric fluorescence difference ratio (ef) can reach as high as 8.41 for mandelic acid and 6.55 for lactic acid. On the contrary, (R,R)-salan-based chiral polymer P-2 shows obvious fluorescence quenching response toward α-hydroxyl carboxylic acids. Most importantly, (R,R)-salen-based polymer P-1 can display bright blue fluorescence color change in the presence of (l)-α-hydroxyl carboxylic acids under a commercially available UV lamp, which can be clearly observed by the naked eyes.     

Regioselective Reduction of 1H-1,2,3-Triazole Diesters

Regioselective reactions can play pivotal roles in synthetic organic chemistry. The reduction of several 1-substituted 1,2,3-triazole 4,5-diesters by sodium borohydride has been found to be regioselective, with the C(5) ester groups being more reactive towards reduction than the C(4) ester groups. The amount of sodium borohydride and reaction time required for reduction varied greatly depending on the N(1)-substituent. The presence of a β-hydroxyl group on the N(1)-substituent was seen to have a rate enhancing effect on the reduction of the C(5) ester group. The regioselective reduction was attributed to the lower electron densities of the C(5) and the C(5) ester carbonyl carbon of the 1,2,3-triazole, which were further lowered in cases involving intramolecular hydrogen bonding.     

Reaction of lithium diphenylphosphonium di(methylide) with carbonic acid derivatives. A novel access to polyfunctional unsaturated esters and amides

The lithium diphenylphosphonium di(methylide) Ph₂ P(CH₂)₂ Li 1 readily attacks cyclic carbonates, carbamates, and thiocarbamates, resulting in “pseudo-acylation” products, after a ring-opening step. Thus, new stabilized ylides are prepared, which can be used in situ as carbonyl olefination reagents towards aldehydes. This procedure is a new one-pot method for the synthesis of (E)-vinylic esters and amides, bearing a free ω-hydroxyl group. When a thiocarbamate is the initial substrate for 1 , a Michael-type cyclization occurs, following the Wittig olefination, resulting in the one-pot preparation of 7-membered heterocycles.     

水溶液中苯乙酮及其降解产物的紫外光光解

在紫外光作用下,水中苯乙酮(10^-^4mol.dm^-^3,pH=6)能发生直接光降解,生成邻羟基和间羟基苯乙酮等中间产物,并且这些产物又可进一步光解生成二羟基苯乙酮。在相同条件下,它们的相对光降解速率大小为:苯乙酮>间羟基苯乙酮>对羟基苯乙酮>邻羟基苯乙酮。     

Catalyst-free and atom-economic synthesis of substituted 1-acetyl and 1-hydroxyl carbazoles

The first-ever Diels-Alder reactions of 3-alkenyl indoles with a conjugated alkynyl ketone are reported. These reactions proceed in an atom-economic manner without a catalyst and give various substituted 1-acetyl carbazoles in moderate to excellent yields. These products can be converted to 1-hydroxyl carbazoles in high yields under mild reaction conditions.     

Selective synthesis of 2-(5-oxo-1-arylhex-1-yn-3-yl)phenyl benzoates via FeCl3-mediated cascade reactions of propargylamines with β-enamino ketones

A mild and efficient FeCl₃-mediated cascade reaction of ortho-hydroxyl propargylamines with β-enamino ketones has been developed. This protocol provided a practical and selective method to synthesize 2-(5-oxo-1-arylhex-1-yn-3-yl)phenyl benzoates via in situ generated alkynyl o-quinone methides following a cascade intermolecular 1,4-conjugate addition/intramolecular nucleophilic addition/reverse Claisen condensation/hydrolysis pathway. Furthermore, a series of 2-(3-oxo-1-arylbutyl)phenyl benzoates with good functional group tolerance were prepared in good to high yields under these reaction conditions.     

Induction of a preferred sense of twist in flexible diphenyls by carbohydrate scaffolds. Synthesis of two "naked" ellagitannin analogous.

The synthesis of "naked" ellagitannin analogues 1 and 2, having a preferred sense of twist of the diphenyl moiety, with a rhamnose and a glucose template, is reported. A clear induction in the chirality of the diphenyl moiety, mediated through a 10-membered ring via ester linkages, was observed. The chiral scaffold of glucose (diequatorial 2,3-hydroxyl groups) exerts a remarkable stronger atropdiastereoselective effect onto the diphenoyl group than the rhamnose ring (axial-equatorial 2,3-hydroxyl groups), according to the Schmidt-Haslam hypothesis.     

Enantioselective total synthesis of (+)-amphidinolide t1

An enantioselective first total syntheis of amphidinolide T1 (1) is described. Amphidinolide T1 (1), a 19-membered macrolide isolated from Amphidinium sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C21 segment 3 by an oxocarbenium ion-mediated alkylation and Yamaguchi macrolactonization sequence. The synthesis of fragment 2 involves an efficient cross metathesis and hydrogenation sequence between the terminal olefins of 5 and 6 to form the C4-C5 carbon-carbon bond. Enol ether 4 is designed to be the surrogate of fragment 3 where the sensitive C16-exo-methylene and the C13-hydroxyl group were protected as the bromoether derivative during the Lewis acid-catalyzed alkylation process. Both stereocenters in fragment 5 as well as the C2 and C3 stereocenters in fragment 4 are accessed by a highly diastereoselective ester-derived titanium enolate-mediated syn-aldol reaction. The bromoether derivative 24 was unraveled at the final stage of the synthesis, providing (+)-amphidinolide T1.     

Electrocatalytic Hydrogen Evolution of the Cobalt Triaryl Corroles Bearing Hydroxyl Groups

Three isomeric A₂B-type new cobalt triaryl corroles bearing hydroxyphenyl substituents have been prepared and well characterized. Their activity and stability in the electrocatalytic hydrogen evolution reaction (HER) have been investigated. The results showed that the hydroxyl position of the phenyl group had significant influence on electrocatalytic HER. The ortho-hydroxyphenyl substituted cobalt corrole ( 1 ) core displays the best HER activity using TsOH proton source, and the turnover frequency (TOF) and catalytic efficiency (C.E) reach 318.68 s⁻¹ and 1.13, respectively. Moreover, a turnover number (TON) of 1447.39 and Faraday efficiency (FE) of 98.7 % have been observed in aqueous medium. The catalytic pathway is via EECEC, EECC or ECEC pathways depending on the acidity of acid proton source (E: electron transfer step, C: chemical step, in this case protonation). The catalytic HER performance of these cobalt corroles follows an order of o-hydroxyl > p-hydroxyl > m-hydroxyl isomer, showing the o- and p-hydroxyl of the phenyl groups are more efficient in accelerating proton relay.     

红霉素A9-（1-异丙氧基环已基）肟的合成及其晶体结构

合成表征了红霉素A9-（1-异丙氧基环已基）肟的E和Z异构体，并在丙酮-水混 合溶液中培养出了前者的单晶，X射线衍射表明，其结构为正交晶系，P2_12_12_1 空间群，晶胞参数：a=2.3101(5) nm, b=2.3761(5) nm, c=0.97066(19)nm, V=5. 3279(8) nm~3，Z=4，μ=0.088 mm~(-1)，F(000)=2064, D_c=1.176 g/cm~3。E-红 霉素A 9-（1-异丙氧基环已基）肟的晶体结构图明显表明1-异丙氧基环已基保护基 确实使十四元大环的构象发生了扭曲，使6-OH的周围空间不再拥挤，从而导致6- OH甲基化的选择性提高。