Syntheses of Strychnos and Aspidospermatan-Type Alkaloids. 8. Selective Total Syntheses of Mossambine and 14-epi-Mossambine by a Radical Cyclization Reaction(1)

Mossambine (6) was obtained by a six-step reaction sequence from the indoloazepine ester 7. Radical cyclization of the tetracyclic vinyl iodide 12a provided a racemic pentacyclic ketone 16E, which could be converted to either enantiomer by condensation with (S or R)-N,S-dimethyl-S-phenylsulfoximine and selective pyrolysis of the resulting diastereomeric alcohols 18 and 19 or 20 and 21. Selective reductions of the resolved (or racemic) ketone 16E provided mossambine (6) and its hydroxy epimer 17.     

Short Syntheses of 4‐Deoxycarbazomycin B,Sorazolon E,and (+)‐Sorazolon E2

Short syntheses of 4‐deoxycarbazomycin B and sorazolon E were established through the condensation of cyclohexanone and commercially available 4‐methoxy‐2,3‐dimethylaniline, followed by Pd^II‐catalyzed dehydrogenative aromatization/intramolecular C−C bond coupling and deprotection. A chiral dinuclear vanadium complex (R _a,S,S )‐ 6 mediated the enantioselective oxidative coupling of sorazolon E, affording (+)‐sorazolon E2 in good enantioselectivity.     

Synthesis of Two Alnustone-Like Natural Diarylheptanoids via 4 + 3 Strategy

The first total synthesis of (4E,6E)-1,7-bis(3,4-dihydroxyphenyl)-hepta-4,6-dien-3-one and an alternative synthesis of (4E,6E)-1,7-bis(4-hydroxyphenyl)-hepta-4,6-dien-3-one, two natural diarylheptanoids, mainly based on Claisen–Schmidt condensation were described. The crucial steps of the syntheses were the condensation of OH-protected 4-aryl-2-butanones with OH-protected 3-aryl-acrylaldehydes by the in situ enamination and then deprotection of OH groups to give the corresponding natural diarylheptanoids.     

Design, synthesis, and 1,3-dipolar cycloaddition of (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1,4-oxazin-2-one N-oxides as chiral (E)-geometry-fixed alpha-alkoxycarbonylnitrones

Optically pure (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1, 4-oxazin-2-one N-oxides [(5R)- and (5S)-2] were designed as chiral (E)-geometry-fixed alpha-alkoxycarbonylnitrones 1. The nitrones (5R)- and (5S)-2 were synthesized by three-step oxidation of (R)- and (S)-phenylglycinols [(R)- and (S)-3], condensation of the resulting (R)- and (S)-2-hydroxylamino-2-phenylethanols [(R)- and (S)-5] with glyoxylic acid, and cyclization of the intermediary nitrones (R)- and (S)-6b. The nitrone (5R)-2reacted with olefins 7-14 under mild conditions to afford the corresponding cycloadducts 15-22 as the main products via the least sterically demanding exo modes. Cycloadduct 30 obtained from (5S)-2 and cyclopentadiene was effectively elaborated to (1S,4S, 5R)-4-benzyloxycarbonylamino-2-oxabicyclo[3.3.0]oct-7-en-3-one (28), the key synthetic intermediate of carbocyclic polyoxin C.     

A novel spectrophotometric method for the simultaneous kinetic analysis of ternary mixtures by mean centering of ratio kinetic profiles

In this paper, a novel and very simple method was developed for the simultaneous spectrophotometric determination of ternary mixtures, without prior separation steps. The method is based on the mean centering of ratio kinetic profiles. The mathematical explanation of the procedure is illustrated. In order to investigate the applicability of the proposed method, it was applied to the simultaneous spectrophotometric determination of hydrazine, phenylhydrazine and acetylhydrazine based on their condensation reactions with p-(dimethylamino)benzaldehyde (DAB) and p-nitrobenzaldehyde (NB) in micellar sodium dodecyl sulfate (SDS) media as a typical ternary mixture. The analytical characteristics of the method such as accuracy, precision, relative standard deviation (R.S.D.) and relative standard error (R.S.E.) were calculated.     

Diastereoselective imino-aldol condensation of chiral 3-(p-Tolylsulfinyl)-2-furaldimine and ester enolates

(Ss)-3-(p-Tolylsufinyl)-2-furaldimine was synthesized, and condensation of the chiral furaldimine with lithium ester enolates has been examined. The product distribution of the reaction is dependent upon reaction conditions and on the kind of the substituent placed on the esters. Disubstituted ester enolate resulted in the exclusive formation of (4R)-beta-lactam, while unsubstituted, tert-butyl ester enolate preferentially gave (3R)-beta-amino ester. With the monosubstituted ester enolates, the condensation afforded (4R)-beta-lactams and/or (3R)-beta-amino esters as major products. This method has been applied to an efficient route to chiral furyl beta-lactams.     

N-氧化吡啶-2-甲醛衍生物的配合物研究(Ⅰ)——与二胺生成的双Schiff碱铜配合物的合成和晶体结构

报道了N-氧化吡啶-2-甲醛(Pio)与乙二胺(en)及1,3-丙二胺(tn)生成的双Schiff碱Cu(Ⅱ)配合物([Cu(Pioen)H_2O](ClO_4)_2和[Cu(Piotn)(H_2O)_2](ClO_4)2)的合成和晶体结构。晶体[Cu(Pioen)H_2O_3(ClO_4)_2属正交晶系,空间群P2_12_12_2,α=7.9534(19),b=7.6768(48),c=26.1037(189),Z=4,R=0.077 1,R_w=0.0771。晶体[Cu(Piotn)-(H_2O)_2](ClO_4)_2属正交晶系,空间群P~(nam),α=7.1360(24)。b=13.7887(42),0=22.2556(81),Z=4,R=0.0491,R_w=0.0491。结构由Patterson函数及Fourier合成法解出,经全矩阵最小二乘法修正至收敛。     

新型含吡唑环的N-甲氧基氨基甲酸甲酯类化合物的设计、合成及生物活性

以苯(吡啶)乙/丙酮类化合物为原料, 经酯化、环化和缩合三步制得新型含吡唑环的N-甲氧基氨基甲酸甲酯类化合物3a~3r, 化合物及其中间体的化学结构经红外光谱、核磁共振谱及元素分析确认. 生物活性结果表明, 化合物3在400 mg/L下分别对水稻稻瘟病、黄瓜霜霉病和小麦白粉病具有很好的防治效果. 对水稻稻瘟病, R₁为甲基或甲氧基取代的苯基时活性最好; 对于黄瓜霜霉病和小麦白粉病, R₁为苯基或甲基取代苯基的化合物杀菌活性优于其它化合物, R₂为甲基的化合物杀菌活性优于R₂为氢的化合物.     

Base-induced decomposition of alkyl hydroperoxides in the gas phase. Part 3. Kinetics and dynamics in HO- + CH3OOH, C2H5OOH, and tert-C4H9OOH reactions

The E(CO)2 elimination reactions of alkyl hydroperoxides proceed via abstraction of an alpha-hydrogen by a base: X(-) + R(1)R(2)HCOOH --> HX + R(1)R(2)C=O + HO(-). Efficiencies and product distributions for the reactions of the hydroxide anion with methyl, ethyl, and tert-butyl hydroperoxides are studied in the gas phase. On the basis of experiments using three isotopic analogues, HO(-) + CH3OOH, HO(-) + CD3OOH, and H(18)O(-) + CH3OOH, the overall intrinsic reaction efficiency is determined to be 80% or greater. The E(CO)2 decomposition is facile for these methylperoxide reactions, and predominates over competing proton transfer at the hydroperoxide moiety. The CH3CH2OOH reaction displays a similar E(CO)2 reactivity, whereas proton transfer and the formation of HOO(-) are the exclusive pathways observed for (CH3)3COOH, which has no alpha-hydrogen. All results are consistent with the E(CO)2 mechanism, transition state structure, and reaction energy diagrams calculated using the hybrid density functional B3LYP approach. Isotope labeling for HO(-) + CH3OOH also reveals some interaction between H2O and HO(-) within the E(CO)2 product complex [H2O...CH2=O...HO(-)]. There is little evidence, however, for the formation of the most exothermic products H2O + CH2(OH)O(-), which would arise from nucleophilic condensation of CH2=O and HO(-). The results suggest that the product dynamics are not totally statistical but are rather direct after the E(CO)2 transition state. The larger HO(-) + CH3CH2OOH system displays more statistical behavior during complex dissociation.     

New resolution of 2-formyl-1,4-dhp derivatives using CIDR methodology. Facile access to new chiral tricyclic thiolactam

(R)- and (S)-alpha-phenylethylamine (alpha-PEA: 7) have been used separately to resolve successfully a racemate 2-formyl-1,4-DHP derivative 4. The process was based on the difference of the solubility of both Schiff bases (6) since one of them crystallized out from the solution. These imines obtained by condensation of (R)-alpha-PEA (7) or (S)-alpha-PEA (7) with aldehyde (rac-4) were separated and analyzed by X-ray diffraction, and their exposition to an hydrochloric hydrolysis conditions led to the enantiopure (4R)-4 or (4S)-4 in excellent yields. Separate condensation of other chiral (8 and 13) and racemic (18) amino thiols as auxiliary with rac-4, (4S)-4, or (4R)-4 is accompanied by an in situ crystallization-induced dynamic resolution, whereby one distereomer of thiazole template selectively precipitates and can be isolated by simple filtration in 76-82% yield with dr > 99. The thiazole species isolated from this process resulted from an amino aldehyde condensation followed by a spontaneous thiol-imine cycloaddition. Finally, the racemate (+/-)-(4R,2'R)-19 and the diastereomerically pure homologous (4S,2'R)-23 and (4R,2'S)-20 (obtained in good yields (79-82%) from 2-aminoethanethiol (18) and 2-formyl-1,4-DHP derivative rac-4, (4S)-4, or (4R)-4, respectively) were converted conveniently in a one-pot procedure into newly tricyclic thiolactams in the DHP series in racemic ((+/-)-(6R,9bR)-21, 72% yield)) and enantiopure ((6S,9bR)-24, 71% yield); (6R,9bS)-24, 70% yield) forms.     

新型Bluco类β-内酰胺酶分子探针的合成

以2-氰基-6-羟基苯并噻唑为原料,与溴乙醛缩二乙醇缩合制得缩醛后再水解合成中间体6-(2-羰乙基)苯并[d]噻唑-2-甲腈(2);7-苯乙酰氨基-3-氯甲基头孢菌烷酸二苯甲酯依次经碘代和Wittig反应得(Z)-3-[3-(2-氰基苯并[d]噻唑-6-氧)丙-1-烯]-8-羰基-7-(2-苯乙酰氨基)-5-噻-1-氮[4.2.0]辛-2-烯-2-甲酸二苯甲酯(5);5经脱保护、缩合和氧化反应合成了3个新的Bluco类似物,其结构经1H NMR,13C NMR和HR-MS(ESI)表征。     

Enantioselective palladium-catalyzed total synthesis of vitamin e by employing a domino Wacker-Heck reaction

An enantioselective total synthesis of vitamin E in which a novel palladium-catalyzed domino reaction was employed as the key step is described. This reaction allows the formation of the chiral chroman framework and the concurrent introduction of part of the side chain of vitamin E. The sequence comprises an enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly, reaction of alkenylphenol 12 with methyl vinyl ketone (13) in the presence of catalytic amounts of Pd(OTFA)(2) (TFA = trifluoroacetate), the enantiopure ligand (S,S)-Bn-BOXAX (8 b; Bn = benzyl, BOXAX = 2,2'-bis(oxazolyl)-1,1'-binaphthyl, and p-benzoquinone (9) as an oxidant gives access to chiral chroman 10 with an enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24 by an aldol condensation reaction with (3R)-3,7-dimethyloctanal (11). Subsequent 1,2-addition of methyllithium, elimination of water, and hydrogenation yields vitamin E.     

不对称Schiff碱镍(Ⅱ)配合物的合成及其晶体结构

合成了3个具有不对称结构的Schiff碱配体H2Ln(n=1、2、3)。H2L1由乙酰丙酮、乙二胺和水杨醛缩合作用得到,H2L2由乙酰丙酮、(1R,2R)-环己二胺和水杨醛缩合作用得到,H2L3由苯甲酰丙酮、乙二胺和水杨醛缩合作用得到,每个反应中3个反应物的物质的量之比均为1∶1∶1。配体H2Ln分别与Ni(OAc)2.4H2O进行配位反应得到3个单核Ni(Ⅱ)配合物1,2和3。分别采用1H NMR、FTIR和元素分析对化合物进行了表征,并通过X-射线单晶衍射技术测定了3个配合物的晶体结构。     

Synthesis of the Carbohydrate Moiety of Glycoproteins from the Parasite Echinococcus granulosus and Their Antigenicity against Human Sera

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the carbohydrate moiety of glycoprotein from Echinococcus granulosus have been accomplished. Trisaccharide Galβ1-3Galβ1-3GalNAcα1-R (A), tetrasaccharide Galα1-4Galβ1-3Galβ1-3GalNAcα1-R (B), and pentasaccharide Galα1-4Galβ1-3Galβ1-3Galβ1-3GalNAcα1-R (C), (R = biotinylated probe) were synthesized by stepwise condensation and/or block synthesis by the use of 5-(methoxycarbonyl)pentyl 2-azido-4,6-O-benzylidene-2-deoxy-α-d-galactopyranoside as a common glycosyl acceptor. The synthesis of the tetrasaccharide and the pentasaccharide was improved from the viewpoint of reducing the number of synthetic steps and increasing the total yield by changing from stepwise condensation to block synthesis. Moreover, hexasaccharide E, which contains the oligosaccharide sequence which occurs in E. granulosus, was synthesized from trisaccharide D. We examined the antigenicity of these five oligosaccharides by an enzyme-linked immunosorbent assay (ELISA). Although compounds of C–E did not exhibit antigenicity against cystic echinococcosis (CE) patient sera, compounds B, D, and E showed good serodiagnostic potential for alveolar echinococcosis (AE).     

Synthesis of a C(29)-C(51) subunit of spongistatin 1 (Altohyrtin A) starting from (R)-3-benzyloxy-2-methylpropan-1-ol

A protected C(29)-C(51) subunit ((+)-38) of spongistatin 1 has been obtained. Key steps involve the aldol condensation of (3S, 4R)-3-methyl-7-[(p-methoxybenzyl)oxy]-4-[(triethylsilyl)oxy]octan- 2-o ne ((-)-6) with (tert-butyl)dimethylsilyl 4-deoxy-2, 3-di-O-(methoxymethyl)-4-methyl-6-O-(tert-butyl)dimethylsilyl)-bet a-D -glycero-L-gluco-heptodialdo-1,5-pyranoside ((+)-7) and a C-glycosidation of (4R,7R&S,E)-7, 8-dichloro-2-methylidene-1-(trimethylsilyl)oct-5-en-4-yl p-methoxybenzoate (16). Aldehyde (+)-7 was derived from (R)-3-benzyloxy-2-methylpropan-1-ol ((+)-10) in 13 formal steps but requiring the isolation of five intermediate products only. The longest linear synthetic scheme converts (+)-10 into (+)-38 in 2% overall yield (isolation of 11 intermediate products).     

Lipase-catalyzed Knoevenagel condensation between α,β-unsaturated aldehydes and active methylene compounds

A simple and efficient Knoevenagel condensation between a b-unsaturated aldehydes and active methylene compounds is reported.Notably,this condensation can be catalyzed by PPL(lipase from porcine pancreas) with satisfied yields(49%–92%).Moreover,PPL induces moderate Z/E selectivity in the Knoevenagel condensation.     

2-(E-2-苯乙烯基)喹啉的合成

以苯甲醛为原料在碱性条件下与丙酮缩合得苄叉丙酮（1），1与邻氨基苯甲醛发生Friedlaender缩合反应得到新的目标产物2－（E－2－苯乙烯基）喹啉(2),产率81％。     

Diastereoselective Synthesis of Glycos-3-yl-α-amino Easters

We report here the diastereoselective synthesis of (2S, 3′R)-(α-D-allofuranos-3-yl) t-butyl glycinate by the condensation of a glycine enolate on the carbonyl function of α-D-ribohexofuranos-3-ulose 2.     

A general, efficient and stereospecific route to sphingosine, sphinganines, phytosphingosines and their analogs

Sphingosine, sphinganines and phytosphingosines and their analogs were synthesized by an aldol condensation between an iminoglycinate bearing a (+)-(1R,2R,5R)-2-hydroxy-3-pinanone group as chiral auxiliary and an appropriate aldehyde. All condensations proceeded with excellent enantioselectivity to generate the (2S,3R)-D-erythro structures in good yields.     

Studies towards the synthesis of ertugliflozin from l-Arabinose

A new method for the diastereoselective synthesis of enantiomerically pure ertugliflozin was developed. The crucial step involves an aldol condensation between 1-(4-chloro-3-(4-ethoxybenzyl)phenyl)ethanone and (4R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyl-5-((trityloxy)methyl)-1,3-dioxolane-4-carbaldehyde, which was prepared from known 2-C-trityloxymethyl-2,3-O-isopropylidene-l-erythrose (easily accessible in three steps from l-arabinose) by standard reduction/oxidation and protection/deprotection manipulations. Dihydroxylation of the aldol condensation product and further global deprotection led to the formation of the target molecule.