Biosynthetic studies of versipelostatin, a novel 17-membered α-tetronic acid involved macrocyclic compound isolated from Streptomyces versipellis

Versipelostatin, a novel microbial metabolite consisting of a 17-membered macrocyclic aglycone with an α-acyltetronic acid functional group and sugar moieties was shown to be biosynthesized through a polyketide intermediate and the involvement of glyceric acid.     

Revision of the absolute configurations of bethosides B and C and their aglycone

The absolute stereochemistry of the steroidal saponins bethosides B and C was previously assigned as (22R,25R) on the basis of work that employed Horeau's method. Our studies of helosides A and B created doubt about both the original assignment and consequently our conclusion that relied upon it. The absolute configurations of bethosides B and C are revised to (22S,25R) following X-ray crystallographic analysis of their aglycone. Synthesis and full spectral characterization of both the 22R and 22S aglycones is reported to facilitate future stereochemical assignments in this series of saponins.     

The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary amines.

A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7. The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an aglycone of osmundalin. On the other hand, the directly conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5-hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.     

Determination of absolute stereochemistry of natural alicyclic glycosides by 1H NMR spectroscopy without application of chiral reagents--an indication

A study has been made of the 1H NMR spectra of peracetylated beta-glucopyranosides and alpha-arabinopyranosides obtained by reaction of D- and L-glucoses, and L- and D-arabinoses with either (R)- or (S)-2-octanols. The obtained and literature data show that 1H NMR spectra may be used to determine the absolute configuration of the aglycone moieties of some alicyclic glycosides without the need to synthesize derivatives with chiral reagents, as long as the absolute configuration of their monosaccharide moiety is known or vice versa. Spectra of marine steroid glycosides and their acetates containing glycosylated side chains as alicyclic fragments were also examined. It was shown that analysis of 1H NMR spectra for the determination of the absolute configuration is more applicable in the cases when glycosides have the same substitution in the D-ring of the aglycone moiety.     

Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry

Negative electrospray ionization tandem quadrupole mass spectrometry was used to study the collision-induced dissociation (CID) of the O-glycosidic bond from different commercially available flavonoid glycosides. Depending on the structure, flavonoid glycosides can undergo both a collision-induced homolytic and heterolytic cleavage of the O-glycosidic bond producing deprotonated radical aglycone ((Y(0) - H)(-*)) and aglycone (Y(0) (-)) product ions. The relative abundance of the radical aglycone to the aglycone fragment from flavonol-3-O-glycosides increased with increasing number of hydroxyl substituents in the B ring and in the order kaempferol - 相似文献   

Antimicrobial activity of sphingolipids isolated from the stems of cucumber (Cucumis sativus L.)

Three antimicrobial sphingolipids were separated by bioassay-guided isolation from the chloroform fraction of the crude methanol extract of cucumber (Cucumis sativus L.) stems and identified as (2S,3S,4R,10E)-2-[(2'R)-2-hydroxytetra-cosanoylamino]-1,3,4-octadecanetriol-10-ene (1), 1-O-β-D-glucopyranosyl(2S,3S,4R,10E)-2-[(2'R)-2-hydroxy-tetracosanoylamino]-1,3,4-octadecanetriol-10-ene (2) and soya-cerebroside I (3) by their physicochemical properties and spectroscopic analysis. They were evaluated to show antifungal and antibacterial activity on test microorganisms including four fungal and three bacterial species. Among them, compound 1, a relatively low polarity aglycone, exhibited stronger antimicrobial activity than its corresponding glycoside 2. The results indicated that sphingolipids could be the main antimicrobial compounds in the crude methanol extract of cucumber stems.     

Synthesis and properties of chiral ammonium-based ionic liquids

New chiral ammonium-based ionic liquids containing the (1R,2S,5R)-(-)-menthyl group can be easily and efficiently prepared under ambient conditions. The preparation and characterization of trialkyl[(1R,2S,5R)-(-)-menthoxymethyl]ammonium salts is reported. The salts have been demonstrated to be air- and moisture-stable under ambient conditions and can be readily used in a variety of standard experimental procedures. The single-crystal X-ray structure of butyldimethyl[(1R,2S,5R)-(-)-menthoxymethyl]ammonium chloride has been determined. The chiral, room-temperature ionic liquids have been characterized by physical properties such as specific rotation, density, viscosity, thermal degradation, and glass transition temperature. Trialkyl[(1R,2S,5R)-(-)-menthoxymethyl]ammonium chloride prototype ionic liquids have also been found to exhibit strong antimicrobial and high antielectrostatic activities.     

人参中达玛烷型皂苷的化学转化产物结构和转化途径研究

利用高效液相色谱-电喷雾-多级串联质谱(HPLC-ESI-MSn)技术分析人参中3种达玛烷型皂苷(三七皂苷R1,人参皂苷Rd、20(S)-Rg3)在12-磷钨酸环境中转化的产物结构和转化途径。由原人参三醇型皂苷R1转化获得9种产物:20(S)-25-OH-R2、20(R)-25-OH-R2、25-OH-T5、20(S)-R2、20(R)-R2、20(S)-25-epoxy-R2、20(R)-25-epoxy-R2、T5、3β,12β-二羟基-6α-(2-O-β-D-吡喃木糖基-β-D-吡喃葡糖氧基)达玛烷-20(22),24-二烯。由原人参二醇型皂苷Rd和20(S)-Rg3转化得到10种产物:20(S)-25-OH-Rg3、20(R)-25-OH-Rg3、25-OH-Rk1、25-OH-Rg5、20(S)-Rg3、20(R)-Rg3、(20S,25)-epoxy-Rg3、(20R,25)-epoxy-Rg3、Rk1、Rg5。通过分析转化产物结构,并考察主要产物含量随转化时间的变化趋势,总结了人参中达玛烷型皂苷在酸性水溶液环境中的转化途径,即通过C20位去糖基化和差向异构化反应,以及烯烃链的水合、脱水、环合反应转化为稀有皂苷。     

Novel rearrangement of an isocaryolane sesquiterpenoid under mitsunobu conditions

Under modified Mitsunobu reaction conditions, a novel skeleton rearrangement of terpenes has been obtained. The reactivity of 8, 9-dioxygenated isocaryolane derivatives has been investigated. When either (8R,9R)-8-methoxyisocaryolane-9-ol (7) or (8R, 9R)-isocaryolane-8,9-diol (10) are treated under acidic conditions, isocaryolan-9-one (9) and the rearrangement compound (1S,2S,5R,8S)-1, 4,4-trimethyltricyclo[6.2.1.0(2,5)]undecane-8-carbaldehyde (11) are obtained. Otherwise treatment of compounds 7 and 10 under modified Mitsunobu conditions leads to the novel sesquiterpene derivative (1S, 2S,5R,9R)-1,4,4-trimethyltricyclo[7.2.1.0(2,5)]dodecan-8-one (8). This is the first example, to our knowledge, of a Mitsunobu-induced pinacol rearrangement. The influences of the substrate and reaction conditions on the evolution of the reaction are both explored. This modification of the Mitsunobu reaction conditions introduces a new, one-pot, procedure for preparing this class of rearrangement product.     

Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes

The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800-3600 cm(-1). Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R?H?3](+), showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R?H?3](+) complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen-bonding interactions between the C(2')-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host.     

Effect of hydrolysis on the yield of hederagenin and High-performance thin-layer chromatography densitometric quantification of hederagenin in fruit pericarp of Sapindus spp

Fruit pericarp of Sapindus species are reported to contain glycosides with hederagenin as an aglycone. To free the aglycone from the glycosides, they need to be hydrolyzed, and the commonly used method is hydrolysis with either hydrochloric or sulfuric acid. In the present work, we studied the effect of hydrolysis on the yield of hederagenin from the fruit pericarp of 3 species of Sapindus, viz., S. mukorossi, S. laurifolius, and S. emarginatus. A high-performance thin-layer chromatography densitometric method for the quantification of hederagenin was developed and validated. It involved automated application of samples as bands onto silica gel 60F254 plates, development with toluene-ethyl acetate-formic acid (7 + 3 + 5, v/v/v) mobile phase, detection with anisaldehyde-sulfuric acid reagent, and scanning at 595 nm. The yield of hederagenin ranged from 0.035 to 1.29% (w/w) with different methods of hydrolysis. Hydrolysis with 3.5 M aqueous sulfuric acid under reflux for 6 h gave the maximum yield of hederagenin in all 3 species, with the highest amount in S. emarginatus (1.29%, w/w).     

New forced degradation products of vildagliptin: Identification and structural elucidation using LC-MS,with proposed formation mechanisms

Abstract

A new and simple RP-HPLC-UV method was developed for well-separation of vildagliptin raw material and its degradation products at different conditions; it uses of ammonium acetate buffer at pH= 7.5 and methanol with Athena C18 -WP (250?mm) column. Results show that six degradants have been identified using LC–MS technique, in addition to the NMR approach in some cases. One degradant at relative retention time (RRT) 1.3 was formed under acidic condition and designated as 2-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) hexahydropyrrolo[1,2-a]pyrazine-1,4-dione at m/z = 304. Three degradants were formed under various conditions of basic hydrolysis at RRTs 1.2, 0.6 and 0.4 with following names and molar masses (m/z), respectively: 1-(((1S, 3S, 5S, 7S)-1,3-dihydroxyadamantan-2-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 337.2, 1-(((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 321.1 and (1,4-dioxo-1,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-3-yl)glycylproline at m/z = 322.6. Another three degradants were also formed under oxidative oxidations of vildagliptin, one at RRT 0.38 and designated as N-hydroxy-N-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) glycinate with m/z 241.1, the second one was identical to that formed under basic hydrolysis at RRT 0.6 and the last one has RRT 0.8 and was identified as (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol at m/z 183.1. Formation mechanisms for the degradation products were described.     

Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin/methymycin polyketide synthase

Picromycin synthase (PICS) is a multifunctional, modular polyketide synthase (PKS) that catalyzes the conversion of methylmalonyl-CoA to narbonolide and 10-deoxymethynolide, the macrolide aglycone precursors of the antibiotics picromycin and methymycin, respectively. PICS modules 5 and 6 were each expressed in Escherichia coli with a thioesterase domain at the C-terminus to allow release of polyketide products. The substrate specificity of PICS modules 5+TE and 6+TE was investigated using N-acetylcysteamine thioesters of 2-methyl-3-hydroxy-pentanoic acid as diketide analogues of the natural polyketide chain elongation substrates. PICS module 5+TE could catalyze the chain elongation of only the syn diketide (2S,3R)-4, while PICS module 6+TE processed both syn diastereomers, (2S,3R)-4 and (2R,3S)-5, with a 2.5:1 preference in k(cat)/K(m) for 5 but did not turn over either of the two anti diketides. The observed substrate specificity patterns are in contrast to the 15-100:1 preference for 4 over 5 previously established for several modules of the closely related erythromycin PKS, 6-deoxyerythronolide B synthase (DEBS).     

Stereospecificity of ketoreductase domains 1 and 2 of the tylactone modular polyketide synthase

Tylactone synthase (TYLS) is a modular polyketide synthase that catalyzes the formation of tylactone (1), the parent aglycone precursor of the macrolide antibiotic tylosin. TYLS modules 1 and 2 are responsible for the generation of antidiketide and triketide intermediates, respectively, each bound to an acyl carrier protein (ACP) domain. Each module harbors a ketoreductase (KR) domain. The stereospecificity of TYLS KR1 and TYLS KR2 has been determined by incubating each of the recombinant ketoreductase domains with reconstituted ketosynthase-acyltransferase [KS][AT] and ACP domains from the 6-deoxyerythronolide B synthase (DEBS) in the presence of the N-acetylcysteamine thioester of syn-(2S,3R)-2-methyl-3-hydroxypentanoate (6), methylmalonyl-CoA, and NADPH resulting in the exclusive formation of the ACP-bound (2R,3R,4S,5R)-2,4-methyl-3,5-dihydroxyhepanoyl triketide, as established by GC-MS analysis of the TMS ether of the derived triketide lactone 7. Both TYLS KR1 and KR2 therefore catalyze the stereospecific reduction of the 2-methyl-3-ketoacyl-ACP substrate from the re-face, with specificity for the reduction of the (2R)-methyl (D) diastereomer. The dehydration that is catalyzed by the dehydratase (DH) domains of TYLS module 2 to give the unsaturated (2E,4S,5R)-2,4-dimethyl-5-hydroxyhept-2-enoyl-ACP2 is therefore a syn elimination of water.     

Highly diastereoselective and stereodivergent dihydroxylations of acyclic allylic amines: application to the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose

Aminohydroxylation of tert-butyl sorbate [tert-butyl (E,E)-hexa-2,4-dienoate] using enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and (-)-camphorsulfonyloxaziridine gives tert-butyl (R,R,R,E)-2-hydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hex-4-enoate in >99:1 dr. Subsequent dihydroxylation under Upjohn conditions (OsO(4)/NMO) gives tert-butyl (2R,3R,4S,5S,αR)-2,4,5-trihydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hexanoate (in 95:5 dr) while dihydroxylation under Donohoe conditions (OsO(4)/TMEDA) proceeds with antipodal diastereofacial selectivity to give the (R,R,R,R,R)-diastereoisomer (in 95:5 dr). The amino triols resulting from these dihydroxylation reactions are useful for further elaboration, as demonstrated by the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose.     

水解动力学拆分3-(1-萘氧基)-1,2-环氧丙烷

研究了3-(1-萘氧基)-1,2-环氧丙烷[(R,S)-1]在Salen Co(Ⅲ)催化下的水解动力学拆分(HKR)。以转化率和ee值为指标,考察了催化剂用量、底物用量、反应温度、反应时间、溶剂种类等对HKR反应的影响。最佳HKR条件为:(R,S)-1 10 mmol,w[Salen Co(Ⅲ)]=0.75%,THF 1 mL,水0.5 eq,于25℃水解40 h,(R,S)-1的转化率为49.5%,(S)-1的ee为99.5%。     

Reduction products of the alkaloid norfluorocurarine

The alkaloid norfluorocurarine was reduced under various conditions to produce the novel bisindoline derivative 2,16-dihydro-19-oxo-C-dihydrotoxiferine and the previously known natural derivatives deoxydihydro-, deoxytetrahydro-, and tetrahydronorfluorocurarine. The structures of the synthesized compounds were identified using IR and UV spectroscopy; of newly produced 2,16-dihydro-19-oxoC-dihydrotoxiferine and deoxydihydronorfluorocurarine, also by x-ray structure analysis. Determination of the absolute configuration of N(α)-methylfluorocurarine chloride dihydrate by x-ray methods enabled the configuration of the 3S,7R,15S asymmetric centers in norfluorocurarine and 2S,3S,7R,15S in deoxydihydronorfluorocurarine to be determined. Also, the absolute configuration of 2,16-dihydro-19-oxoC-dihydrotoxiferine was determined as 2S,3S,7R,15R,16R in one part of the bisindoline and 3'S,7'R,15'S in the other.     

瑞波西汀关键中间体的合成

瑞波西汀在抑郁症的短期和长期治疗中均表现出有效和耐受性，而且（S，S）型立体异构体的抗抑郁能力最高，作者研究了反式肉桂醇的不对称环据氧化，在温和条件下，采用全家的过氧化氢，在D－果糖衍生物催化下得到了（S，S）构型瑞波西汀关键中间体（R，R）肉桂醇环氧化物，获得了高产率和立体选择性。     

Electron impact mass spectral fragmentation of chiral bisbenzoxazole,bisbenzothiazole and biscarbamide derivatives of 2,2-dimethyl-1,3-dioxolane

The mass spectrometric fragmentation behaviour of five pairs of (R,R)- and (S,S)-4,5-bis(benzoxazol-2-yl)-2,2-dimethyl-1,3-dioxolane derivatives, one pair of (R,R)- and (S,S)-4,5-bis(benzothiazol-2-yl)-2,2-dimethyl-1,3-dioxolanes, and three pairs of (R,R)- and (S,S)-N,N'-bis(2-hydroxyaryl)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbamides, all important compounds for asymmetric catalysis (P. Jiao et al., Tetrahedron Asymmetry 2001; 12: 3081), has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization conditions. The spectral observations have been rationalized in terms of fragment ion structures and fragmentation mechanisms that will provide an aid to spectral interpretation for new compounds of this type.     

Mechanistic insights into the proline-directed enantioselective heterogeneous hydrogenation of isophorone

The adsorption rates onto a range of platinum single-crystal surfaces of key species involved in the proline-directed heterogeneous enantioselective hydrogenation of isophorone were investigated by electrochemical means. Specifically, the uptakes of the prochiral reactant (isophorone), the chiral hydrogenation product (3,3,5-trimethylcyclohexanone), and the chiral directing agent ((R)- and (S)-proline) were examined. The effects of R,S chiral kink sites on the adsorption of (R,S)-proline were also studied. The reactant adsorbs approximately 105 times faster than the chiral modifier so that under conditions of competitive adsorption the latter is entirely excluded from the metal surface. Supplementary displacement and reaction rate measurements carried out with practical Pd/carbon catalysts show that under certain reaction conditions isophorone quickly displaces preadsorbed proline from the metal surface. Thus both kinetics and thermodynamics ensure that the chiral modifier can play no role in any surface-mediated process that leads to enantiodifferentiation. These results are fully consistent with the recent proposal1 that the crucial step leading to enantiodifferentiation occurs in the solution phase and not at the metal surface. In addition, it is found that there is no preferred diastereomeric interaction between (R,S)-proline and R,S step kink sites on Pt{643} and Pt{976}, implying that such sites do not play a role in determining the catalytic behavior of supported metal nanoparticles.