Syntheses and Structure-Odor Relationship of Some γ-Lactones

A lot of norbornene derivatives and lactones are widely used as fragrant components in food or cosmetics. We expected that a series of new compounds with better odor character could be obtained when these two skeleton structures were combined. Thus, a series of endoand exo-5,5-disubstituted-3-oxo-4-oxatricyclo[5,2,1,0;]dec-8-enes（Ⅰ） were synthesized.

Chemoselective synthesis of δ-lactones via benzyl radical cyclization utilizing K_2S_2O_8-CuCl_2

Direct chemoselective oxidation of δ-lactones via highly stable benzyl radical cyclization is reported. The one-pot conversion of premade substituted 5-aryl pentanoic acid and 8-benzyl-1-naphthoic acid in the presence of K2S2Os--CuCl2 results to the δ-lactones in moderate to good yields. The advantages of this methodology is using water as a solvent and utilizing available starting materials.

Stereoselective Addition of Organotitanium and Grignard Reagents to 3,5-O-isopropylidene-L-glucurono-γ-lactone

Substituted PhMgX and PhTi(OCHMe2)4MgX react with 3,5-O-isopropylidene-L-glucurono-γ-lactone 4 to give tetrads 5a-e and its stereoisomers 6a-e Tetrads 5a-e are the important intermediates in the synthesis of howiinol Al and its derivatives. The stereoselectivities of substituted PhTi(OCHMe2)4Mg (5a-e:6a-e ratio, 68-72:32-28) were better than those of substituted PhMgX(33-64:67-36) in the reaction. The effects of different substitUted groups and positions (p-Me, m-Me, o-MeO, p-Cl) of the phenyl ring on their stereoselectivies were not significant.

cDNA Fragment Cloning of L-Galactono-1,4-Lactone Dehydrogenase andIt＇s Expression in Different Organs of R. roxburghii Tratt

A 855 bp cDNA encoding L-galactono-1,4-lactone dehydrogenase (GalLDH) fragment was cloned from fruit of R. roxburghii Tratt by the method of RT-PCR, on the basis of the homologous genes of Arabidopsis thaliana, cauliflower, sweet potato, strawberry, etc. in GenBank. Sequence analysis showed 79-92% identity in nucleotide sequence and 75-87% identity in amino acid sequence to that of strawberry and Arabidopsis thaliana, etc. Northern blot showed that the expression of GalLDH was significantly different in different organs. The transcription level of GalLDH in fruit was significantly higher than that in leaf, stem and root respectively. Furthermore, this expression mode was highly correlated with AsA levels.

Chemical Constituents from Fruits of Rosa davidii

From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2 alpha, 3 beta, 19 beta -trihydroxyl-olean-12-en-28-oic acid (1), 2 alpha, 3 beta -dihydroxyl-urs-28 (13)-lactone (2), arjunic acid (3), euscaphic acid (4), 2 alpha, 3 beta -dihydroxyl-urs-12-en-28-oic acid (5), oleanolic acid (6), kaempferol (7), tiliroside (8), quercetin (9), daucosterol (10) and beta -sitosterol (11). Among them, 1 and 2 were new compounds.

Two New Tetranortriterpenoids from Amoora dasyclada

Two new tetranortriterpenoids 3-oxo-24, 25, 26, 27-tetranortirucall-7-ene-23(21)- lactone, 3á-hydroxy-24, 25, 26, 27-tetranortirucall-7-ene-23(21)-lactone were isolated from Amoora dasyclada. Their structures were elucidated by spectroscopic evidences.

Studies on the Total Synthesis of Hainanolide (VI)-The First Access to the Lactone Functionality

C-2a- beta-H ketone 6 was synthesized from the exo-IMDA-additive 4 with the aid of singlet oxygen, and ring E of hainanolide was assembled via kinetic enol ether of 6.

DMAP-Catalyzed [4＋2] Cycloaddition of α,β-Unsaturated Carboxylic Acids with Ketones for Synthesis of ,β-Unsaturated δ-Lactones （pages 397–400）

The DMAP-catalyzed [4＋2] cycloaddition of α,β-unsaturated carboxylic acids with ketones furnishing α,β-unsaturated δ-lactones in good yields （up to 80%） is described, which is the first example of remote -C（sp^3）-H activation of α,β-unsaturated carboxylic acids facilitated by DMAP, a pyridine-based catalyst.

Formation of β-Lactones by [2＋2] Cycloaddition of Dichloroketene with Unreactive Carbonyl Compounds

We report a modified process that dichloroketene generated in situ from trichloroacetyl chloride and Zn powder reacts with unreactivate carbonyl groups to afford dichloro-β-lactones in moderate to good yields. Subse- quently, monochloro-β-lactones, β-lactones and β-hydroxy ester are obtained by dechlorination under different reac- tion conditions.

Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB

Damsin (1) is a natural pseudoguaianolide sesquiterpene that inhibits NF-κB, a protein complex that controls the transcription of DNA in mammalian cells, and has a potential for standing model for the development of new anti-cancer lead structures. In order to do a preliminary structure-activity study and improve the anti-cancer activity, fourteen derivatives and analogs were prepared and evaluated. These were chosen to represent both structural diversity and structural novelty. The importance of α methylene-γ-lactone moiety for the anti-cancer activity was confirmed, even though other features in the scaffold were shown to be important for the activity. In some cases a new substitution negatively affected the initial activity, however, two analogues, indolo [3,2-c]-4-desoxydamsin (5) and ambrosin (6), were found to be more potent.

Research progress of synthetic lactacystin and its analogs as β-lactone proteasome inhibitors

As Bortezomib and Carfilzomib are approved to treat refractory multiple myeloma, 20 S proteasome has become a highly interested tumor therapeutic target. Because of drug resistance of Bortezomib and Carfilzomib, β-lactone natural products are used to treat cancer, arthritis, asthma, and Alzheimer’s diseases. Now the second generation drug candidates are developed, eg. Salinosporamide A（1）. This review is aiming to encapsulate the synthetic methods of β-lactone proteasome inhibitors, lactacystin（3） and its analogs.

Catalytic and highly stereoselectiveβ-mannopyranosylation using a 2,6-lactone-bridged mannopyranosyl ortho-hexynylbenzoate as donor

An efficient and catalytic protocol for highly stereoselective construction ofβ-mannopyranosylation has been developed.Glycosylation of 2,6-lactone-bridged mannopyranosyl ortho-hexynylbenzoate with various acceptors proceeded smoothly in the presence of 5%Hg(Ⅱ)at room temperature,resulting in the correspondingβ-mannosides in high yield and exclusiveβ-stereoselectivity.

Homogentisic acid γ-lactone suppresses the virulence factors of Pseudomonas aeruginosa by quenching its quorum sensing signal molecules

Bacterial quorum sensing（QS） molecules are involved in the coordination of certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS molecules（autoinducers） and their corresponding receptors have been recognized as important therapeutic targets for drug-resistant infections and biofilm-associated infections（BAI）. This study assessed the multiple biological effects of homogentisic acid y-lactone（HgAL）, a furanone derivative. The anti-QS and anti-biofilm effects of HgAL against PAO1 strain were evaluated using CLSM, SEM, HPLC and other biochemical methods The results showed that HgAL could effectively inhibit the production of pyocyanin and extracellular matrix, as well as reduce the adherence ability and biofilm formation of Pseudomonas aeruginosa. Inhibition of virulence is attributed to the suppressive effect of HgAL on biosynthesis of 3-oxo-C12-HSLand C4-HSL（two kinds of QS signaling molecules in P. aeruginosa）. Our results support HgAL as a potential agent for prevention of BAI in the healthcare settings.

Alterations in Ascorbic Acid Levels by Transformation of the L-galactono-1,4-lactone Dehydrogenase Gene in Solanum tuberosum

L-galactono-1, 4-lactone dehydrogenase(GLDH) is an important enzyme that catalyzes the last step of the ascorbate biosynthetic pathways in plants. A full-length c DNA clone encoding GLDH was isolated from potato(Solanum tuberosum L. ‘Favorita') leaf and subcloned into a binary vector, p BI121, to construct sense and antisense recombinant plant expression vectors. The recombinants were introduced into potato via Agrobacterium-mediated transformation, and plants were confirmed as transgenic using PCR and quantitative real-time PCR. Two anti-sense potato lines(G1 and G2) and three sense lines(G3, G4 and G5) were obtained. The GLDH activity of G4 and G5 were increased in vivo. Moreover, the ascorbic acid(As A) and dehydroascorbate(DHA) contents were up-regulated in both leaves and tubers. However, the shoots of G1 were suppressed and its leaves were deformed. Additionally, the As A contents in G1 leaves and tubers decreased by 28.8% and 10.3%, respectively. The GLDH activity in leaves treated with L-galactono-1,4- lactone(L-Gal L) increased in all lines, as did the As A and DHA contents. These results indicate that GLDH activity plays an important role in regulating the As A level as well as the growth and development of potato plants.

Unexpected Grob-type fragmentation of vinylogous β-silyloxy-cyclobutanone into γ-lactone

An unusual formal oxy transposition of vinylogous β-silyloxy-cyclobutanone 1（a 1,5-difunctionalized substrate） under mild acidic conditions（aqueous HF in CH3CN at 0℃） to the decalinic y-lactone 2 was described.A plausible mechanistic pathway involving the Grob-type fragmentation and intramolecularγ-Iactonization was proposed.

Fe(III)-Catalyzed Aerobic Oxidation of 1,4-Diols

Comprehensive Summary Aerobic oxidation has been catching more and more attention because of its atom economy and environmental friendliness.Oxidation of diols is a challenge due to various oxidative products.Thus,highly selective aerobic oxidation affording specific products is of current interest.In this work,a combination of Fe(NO_(3))_(3)·9H_(2)O/TEMPO/KCl catalysis has been identified as an efficient recipe for the aerobic oxidation of 1,4-diols affordingγ-butyrolactones under mild conditions.The reaction exhibits decent chemo-and regioselectivity of symmetrical and unsymmetrical 1,4-diols.The optically activeγ-lactones may also be prepared from optically active 1,4-diols without erosion of the ee via this method.Furthermore,this approach was successfully applied to synthesize NBP,a commercial drug.

皮孔葱臭木化学成分的研究

目的对皮孔葱臭木Dysoxylum lenticellatum茎干的化学成分及其细胞毒活性进行研究。方法利用正相硅胶、RP-18柱色谱、葡聚糖凝胶Sephadex LH-20等手段进行分离纯化,根据波谱数据鉴定化合物的结构,采用MTT法进行细胞毒活性测定。结果分离鉴定了12个化合物,分别为β-谷甾醇(1)、豆甾醇(2)、3-oxo-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone(3)、3α-hydroxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone(4)、laxiracemosin H(5)、laxiracemosin B(6)、24,25-epoxy-tirucall-7-ene-3,23-dione(7)、丁酰鲸鱼醇(8)、齐墩果酸(9)、蒲公英赛酮(10)、蒲公英赛醇(11)和8-hydroxy-6-methoxy-3-pentylisocoumarin(12)。结论 12个化合物均为首次从该种植物中分离得到,化合物8、10～12为首次从该属植物中分离得到,化合物5、6是甘遂烷型生物碱,化合物3具有明显体外肿瘤细胞生长抑制活性。

华南忍冬花蕾中1个新的单萜苷类化合物

目的 研究华南忍冬Lonicera confusa干燥花蕾(山银花)的化学成分。方法 综合应用HP-20、硅胶、ODS、Sephadex LH-20和半制备液相等多种色谱学方法进行分离纯化,并根据化合物的理化性质和核磁共振波谱数据进行结构鉴定。采用LPS诱导小鼠巨噬细胞RAW264.7模型,以抑制炎性细胞因子一氧化氮(NO)的分泌为评价指标对分离得到的化合物进行体外抗炎活性评价。结果 从华南忍冬干燥花蕾70%乙醇提取物中分离鉴定了5个化合物,分别为8-[α-L-arabinopyranosyl-(1′′→6′)-β-D-glucopyranosyl]-2,6-dimethyloct-1,2′′-lactone(1)、天师酸(2)、黄麻脂肪酸F(3)、天师酸甲酯(4)和黄麻脂肪酸F甲酯(5)。结论 化合物1为新的单萜苷类化合物,命名为忍冬单萜A,化合物2~5为首次从忍冬属植物中分离得到。化合物对LPS诱导的RAW264.7细胞中NO的分泌均无显著的抑制作用。

Improvement of Kdo’s efficient large-scale chemical synthesis method

Kdo residues are widely distributed in bacteria.They are components of bacterial lipopolysaccharide(LPS)and capsular polysaccharides,which can be recognized by the human adaptive immune system,and have great potential for developing new sugar chips and antibacterial vaccines.By improving the existing methods,we optimized the Kdo chemical synthesis method,which was able to efficiently synthesize Kdo monosaccharides with high purity,laying a foundation for the construction of subsequent compound libraries.Kdo acylation can easily form 1,5-lactones and reduce the efficiency of synthesis.By changing the synthesis sequence,we avoided the formation of Kdo 1,5-lactones,improved the synthesis efficiency of Kdo glycals,and provided a new strategy for derivatization.

A Short Synthesis of Clionamine D

Herein we describe a scalable four-step preparation of a-methylene-y-lactone 3 from steroidal sapogenin. This method allowed a facile synthesis of clionamine D, a natural aminosteroid with potent autophagy bioactivity and unprecedented chemical structure.