- Facile synthesis of deuterium-labelled geranylgeraniols
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Facile and stereoselective syntheses of three different kinds of deuterium-labelled geranylgeraniol analogs have been achieved. LiAlD4 is used as the deuterium source to ensure high deuterium incorporation. [8,8-d2]- and [9,9-d2]- geranylgeraniols have been prepared for the first time. [10-d]- geranylgeraniol was efficiently prepared with a high degree of deuterium incorporation.
- Totsuka, Yusuke,Ueda, Shota,Shinada, Tetsuro,Kuzuyama, Tomohisa
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Read Online
- Synthesis of a phosphoantigen prodrug that potently activates Vγ9Vδ2 T-lymphocytes
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Phosphoantigen-sensitive Vγ9Vδ2 T cells are important responders to infections and malignancy. However, the mechanisms by which phosphoantigens stimulate Vγ9Vδ2 T cells are unclear. Here, we synthesized phosphoantigen prodrugs and used them to demonstrate that intracellular delivery of phosphoantigens is required for their activity. The pivaloyloxymethyl prodrug is the most potent phosphoantigen described to date, with stronger stimulation of Vγ9Vδ2 T cells from human peripheral blood and greater ability to induce lysis of Daudi lymphoma cells relative to the previously most potent compound, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP). We demonstrate high binding affinity between phosphoantigens and the intracellular region of butyrophilin 3A1 (BTN3A1), localized to the PRY/SPRY (B30.2) domain, but also affecting the membrane proximal region. Our findings promote a phosphoantigen prodrug approach for cancer immunotherapy and unravel fundamental aspects of the mechanisms of Vγ9Vδ2 T cell activation.
- Hsiao, Chia-Hung Christine,Lin, Xiaochen,Barney, Rocky J.,Shippy, Rebekah R.,Li, Jin,Vinogradova, Olga,Wiemer, David F.,Wiemer, Andrew J.
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Read Online
- The Application of 1,2-Oxazinanes as Chiral Cyclic Weinreb Amide-Type Auxiliaries Leading to a Three-Component, One-Pot Reaction
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1,2-Oxazines were synthesised via a copper-catalysed aerobic acyl nitroso Diels-Alder reaction from 1,4-disubstituted 1,3-dienes and N-Boc-hydroxylamine. From this, 1,2-oxazinanes were obtained in a novel follow-up reaction path. The stability of several 1,2-oxazines and 1,2-oxazinanes towards organometallic compounds was tested to rate their operability as cyclic chiral Weinreb amide auxiliaries. 3,6-Di-tertbutyl-1,2-oxazinane gave the best results and was introduced as a chiral Weinreb amide-type auxiliary to yield chiral α-substituted ketones in a diastereomeric ratio of up to 98:2. The removal of the auxiliary can be performed with BuLi to form unsymmetrical α-chiral ketones. Thereafter, the chiral auxiliary can be re-isolated and purified by sublimation under vacuum.
- F?hrmann, Jan,Hermann, Ludmila,Hilt, Gerhard
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- Using Terpene Synthase Plasticity in Catalysis: On the Enzymatic Conversion of Synthetic Farnesyl Diphosphate Analogues
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Four synthetic farnesyl diphosphate analogues were enzymatically converted with three bacterial sesquiterpene synthases, including β-himachalene synthase (HcS) and (Z)-γ-bisabolene synthase (BbS) from Cryptosporangium arvum, and germacrene A synthase (SmTS6) from Streptomyces mobaraensis. These enzyme reactions not only yielded several previously unknown compounds, showing that this approach opened the door to a new chemical space, but substrates with blocked or altered reactivities also gave interesting insights into the cyclisation mechanisms and the potential to catalyse reactions with different initial cyclisation modes.
- Hou, Anwei,Dickschat, Jeroen S.
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supporting information
p. 15644 - 15649
(2021/10/04)
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- Gold-Catalyzed Formal Hexadehydro-Diels-Alder/Carboalkoxylation Reaction Cascades
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A dual gold-catalyzed hexadehydro-Diels-Alder/carboalkoxylation cascade reaction is reported. In this transformation, the gold catalyst participated in the hexadehydro-Diels-Alder step, switching the mechanism from a radical type to a cationic one, and then the catalyst activated the resulting aryne to form an ortho-Au phenyl cation species, which underwent a carboalkoxylation rearrangement rather than the expected aryne-ene reaction.
- Wang, Hong-Fa,Guo, Lin-Na,Fan, Zhi-Bo,Tang, Tian-Hua,Zi, Weiwei
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supporting information
p. 2676 - 2681
(2021/04/12)
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- A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols
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A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C2. This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.
- Munyemana, Fran?ois,Patiny, Luc,Ghosez, Léon
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- METHODS OF SYNTHESIZING FARNESYL DIBENZODIAZEPINONES
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The present invention is directed to synthetic means for producing farnesyl dibenzodiazepinone compounds, including AMO-01.
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Paragraph 0082-0083
(2021/12/08)
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- Nickel-Catalyzed Asymmetric Reductive 1,2-Carboamination of Unactivated Alkenes
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Starting from diverse alkene-tethered aryl iodides and O-benzoyl-hydroxylamines, the enantioselective reductive cross-electrophilic 1,2-carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β-chiral amines with an enantioenriched aryl-substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.
- He, Jun,Xue, Yuhang,Han, Bo,Zhang, Chunzhu,Wang, You,Zhu, Shaolin
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p. 2328 - 2332
(2020/01/08)
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- Visible-Light-Promoted Intramolecular α-Allylation of Aldehydes in the Absence of Sacrificial Hydrogen Acceptors
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We report herein an unprecedented protocol for radical cyclization of aldehydes with pendant alkenes via synergistic photoredox, cobaloxime, and amine catalysis. The transformation was achieved in the absence of external oxidants, providing a variety of 5-, 6-, and 7-membered ring products with alkene transposition in satisfactory yields. The reaction exhibits wide functional group compatibility and occurs under mild conditions with extrusion of H2.
- Liu, Feng,Liu, Jia-Li,tu, Jia-Lin
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p. 7369 - 7372
(2020/10/05)
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- Scalable synthesis of the aroma compounds d6-β-ionone and d6-β-cyclocitral for use as internal standards in stable isotope dilution assays
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C13 Norisoprenoids are important aroma compounds in wine, giving positive attributes to the overall wine aroma even when found at very low levels. β-Ionone is considered one of the most important aroma compounds giving violet, woody and raspberry aromas to wine, fruits and vegetables in which it is found. Due to its potent aroma at low levels, precise analytical methods are desired for its quantification. Stable isotope dilution assay (SIDA) is one of the most important of these methods but requires the use of isotopically labelled standards. Herein, we describe the scalable synthesis of d6-β-ionone and d6-β-cyclocitral, another aroma compound with smokey and fruity notes, starting from the relatively inexpensive deuterated starting material d6-acetone.
- Mosaferi, Shabnam,Jelley, Rebecca E.,Fedrizzi, Bruno,Barker, David
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- Enzymatic Synthesis of Methylated Terpene Analogues Using the Plasticity of Bacterial Terpene Synthases
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Methylated analogues of isopentenyl diphosphate were synthesised and enzymatically incorporated into methylated terpenes. A detailed stereochemical analysis of the obtained products is presented. The methylated terpene precursors were also used in conjunction with various isotopic labellings to gain insights into the mechanisms of their enzymatic formation.
- Dickschat, Jeroen S.,Hou, Anwei,Lauterbach, Lukas
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supporting information
(2020/02/11)
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- Synthesis method of 5,5,5-trichloro-2-methyl-2-pentene
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The invention provides a synthetic method of 5,5,5-trichloro-2-methyl-2-pentene. The synthetic method comprises the following steps: taking 2-methyl-3-butene-2-ol as an initial compound of a reaction;adding a haloid acid into the reaction system, and conducting distilling to obtain an intermediate product 1-halo-3-methyl-2-butene; adding the intermediate product and chloroform into a reaction kettle, conducting stirring at a low temperature, and adding an inorganic base into the system in batches; wherein the reaction temperature is 0-40 DEG C, the reaction time is 2-10 hours, the mass ratioof the 2-methyl-3-butene-2-ol to the haloid acid in the reaction is (0.3-1):1, the weight ratio of the chloroform to the 1-halo-3-methyl-2-butene is (1-10):1, and the weight ratio of the inorganic base to the 1-halo-3-methyl-2-butene is (0.1-2.0):1. The method is high in reaction yield and low in environmental pollution degree, and the corrosion degree of equipment is reduced.
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Paragraph 0022; 0023
(2019/06/30)
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- Silver-promoted cascade radical cyclization of γ,δ-unsaturated oxime esters with P(O)H compounds: synthesis of phosphorylated pyrrolines
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A cascade radical cyclization was realized for the first silver-promoted imino-phosphorylation of γ,δ-unsaturated oxime esters, which provided a step-economical and redox-neutral route to access a variety of phosphorylated pyrrolines in good to excellent yields. Moreover, a new bulky trivalent phosphine ligand with a pyrroline motif was obtained through a deoxidation process.
- Chen, Chen,Bao, Yinwei,Zhao, Jinghui,Zhu, Bolin
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supporting information
p. 14697 - 14700
(2019/12/11)
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- ANTICOAGULANT COMPOUNDS AND THEIR USE
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According to the invention there is provided a compound of formula (I): wherein R1, R2, R3 and n have meanings given in the description, or a pharmaceutically acceptable solvate, salt or prodrug thereof for use as an anticoagulant.
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- Squalene-Hopene Cyclase: On the Polycyclization Reactions of Squalene Analogues Bearing Ethyl Groups at Positions C-6, C-10, C-15, and C-19
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Squalene-hopene cyclase (SHC) has been found to convert acyclic squalene into 6,6,6,6,5-fused pentacyclic triterpenes hopene and hopanol. The enzymatic reactions of squalene analogues bearing ethyl groups in lieu of methyl groups at positions C-6, C-10, C-15, and C-19 have been examined to investigate whether the larger ethyl substituents (a C1 unit increment) are accepted as substrates and to investigate how these substitutions affect polycyclization cascades. Analogue 6-ethylsqualene 19a did not cyclize, which indicates that substitution with the bulky group at C-6 completely inhibited the polycyclization reaction. In contrast, 19-ethylsqualene 19b afforded a wide spectrum of cyclization products, including mono-, bi-, tetra-, and pentacyclic products in a ratio of 6:6:1:2. The production of tetra- and pentacyclic scaffolds suggests that the reaction cavity for D-ring formation site is somewhat loosely packed and can accept the 19-ethyl group, and that a robust hydrophobic interaction exists between the 19-ethyl group and the binding site. In contrast to 19b, 10-ethylsqualene 20a and 15-ethylsqualene 20b afforded mainly mono- and bicyclic products, that is, the polycyclization cascade terminated prematurely at the bicyclic reaction stage. Therefore, the catalytic domains for the 10- and 15-methyl binding sites are tightly packed and cannot fully accommodate the Et substituents. The cyclization pathways followed by the ethyl-substituted substrates in the presence of SHC and lanosterol and β-amyrin synthases are compared.
- Takahashi, Kazunari,Sasaki, Yusuke,Hoshino, Tsutomu
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supporting information
p. 1477 - 1490
(2018/04/06)
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- Propene as an Atom-Economical Linchpin for Concise Total Synthesis of Polyenes: Piericidin A
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A concise and convergent total synthesis of piericidin A is disclosed. The synthesis hinges on the utilization of propene as a synthetic linchpin to merge the properly elaborated alkyne fragments, leading to the 1,3,6-triene motif of piericidin A. Utilization of propene as a unique alkene, capable of sequential coupling with two alkynes, is further illustrated in the context of various 1,3,6-triene products. The latter process proceeds with high atom economy and efficiently gives rise to complex frameworks from readily accessible alkyne substrates. This strategic C-C bond formation offers an orthogonal paradigm in the design of synthetic routes, leading to higher step economy and more efficient syntheses of polyunsaturated natural products.
- Trost, Barry M.,Gholami, Hadi
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supporting information
p. 11623 - 11626
(2018/09/21)
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- Palladium-Catalyzed Carbocyclizations of Unactivated Alkyl Bromides with Alkenes Involving Auto-tandem Catalysis
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The development of a general catalytic system for the palladium-catalyzed carbocyclization of unactivated alkyl bromides with alkenes is described. This approach uses a commercially available bisphosphine ligand and avoids the use of carbon monoxide atmosphere present in prior studies involving alkyl iodides. Detailed mechanistic studies of the transformation are performed, which are consistent with auto-tandem catalysis involving atom-transfer radical cyclization followed by catalytic dehydrohalogenation. These studies also suggest that reactions involving alkyl iodides may proceed through a metal-initiated, rather than metal-catalyzed, radical chain process.
- Venning, Alexander R. O.,Kwiatkowski, Megan R.,Roque Pe?a, Joan E.,Lainhart, Brendan C.,Guruparan, Akil A.,Alexanian, Erik J.
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supporting information
p. 11595 - 11600
(2017/08/30)
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- β-Amyrin Biosynthesis: Effect of Steric Bulk at the 6-, 10- and 15-Positions in the 2,3-Oxidosqualene Backbone on Polycyclisation Cascades
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β-Amyrin synthase incubation experiments have been conducted to determine the influence of steric effects at the 6-, 10- and 15-positions of 2,3-oxidosqualene on the polycyclisation pathway. Nor- and ethyl-substituted oxidosqualene analogues were synthesised. Cyclisation of the ethyl-substituted analogues did not occur, but the nor analogues underwent a polycyclisation cascade to yield fully cyclised products with 6/6/6/6/6-fused pentacyclic scaffolds generated via a final oleanyl cation. Previously, we reported that 19- and 23-ethyl-substituted analogues underwent polycyclisation reactions. Therefore, the catalytic domain involved in earlier cyclisation steps is notably compact. In contrast, the catalytic domain in the later cyclisation steps is more loosely packed (less compact) to accommodate the bulky ethyl group. The reaction cavities for recognising branched methyl groups are discussed by comparing β-amyrin synthase with other triterpene cyclases such as lanosterol and hopene synthases.
- Terasawa, Yuri,Sasaki, Yusuke,Yamaguchi, Yuki,Takahashi, Kazunari,Hoshino, Tsutomu
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p. 287 - 295
(2017/01/24)
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- Copper-free arylation of 3,3-disubstituted allylic halides with triazene-softened aryl Grignard reagents
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A copper-free allylic arylation reaction between 3,3-disubstituted allylic halides and triazene-softened aryl Grignard reagents has been developed. This protocol presents a direct and efficient way to construct both α- or γ-isomers with high regioselectivity under environmentally benign conditions. Various functional groups can be tolerated in the reaction and the products are of high value for multiple synthetic applications. The α- and γ-isomers can be converted to the corresponding 3H-indole and indole derivatives in multigram scale respectively.
- Xu, Lijun,Liu, Zhubo,Dong, Weipeng,Song, Jinyu,Miao, Maozhong,Xu, Jianfeng,Ren, Hongjun
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supporting information
p. 6333 - 6337
(2015/06/08)
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- Conformational Analysis, Thermal Rearrangement, and EI-MS Fragmentation Mechanism of (1(10)E,4E,6S,7R)-Germacradien-6-ol by 13C-Labeling Experiments
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An uncharacterized terpene cyclase from Streptomyces pratensis was identified as (+)-(1(10)E,4E,6S,7R)-germacradien-6-ol synthase. The enzyme product exists as two interconvertible conformers, resulting in complex NMR spectra. For the complete assignment of NMR data, all fifteen (13C1)FPP isotopomers (FPP=farnesyl diphosphate) and (13C15)FPP were synthesized and enzymatically converted. The products were analyzed using various NMR techniques, including 13C, 13C COSY experiments. The (13C)FPP isotopomers were also used to investigate the thermal rearrangement and EI fragmentation of the enzyme product. All 15 isotopomers of (13C1)- and fully labeled (13C15)farnesyl diphosphate were synthesized and converted to the title compound by a newly characterized bacterial terpene cyclase from Streptomyces pratensis. The enzyme products were used for structure elucidation of the sesquiterpene alcohol, full assignment of NMR data and a conformational analysis, and investigation of its Cope rearrangement and of its EI-MS fragmentation mechanism.
- Rabe, Patrick,Barra, Lena,Rinkel, Jan,Riclea, Ramona,Citron, Christian A.,Klapschinski, Tim A.,Janusko, Aron,Dickschat, Jeroen S.
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p. 13448 - 13451
(2015/11/09)
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- Nickel-Catalyzed Regioselective Reductive Cross-Coupling of Aryl Halides with Polysubstituted Allyl Halides in the Presence of Imidazolium Salts
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The nickel-catalyzed direct reductive cross-coupling of aryl halides with readily accessible polysubstituted allyl halides provides an efficient method for preparing diverse allylated arenes under mild conditions. Both allyl bromides and allyl chlorides are compatible with the transformation.
- Zhang, Zhan,Xu, Lijun,Chen, Zhengkai,Liu, Zhubo,Miao, Maozhong,Song, Jinyu,Ren, Hongjun
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p. 2784 - 2788
(2015/12/18)
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- Synthesis of 3-aza-bicyclo[3.1.0]hexan-2-one derivatives via gold-catalyzed oxidative cyclopropanation of N -allylynamides
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N-Allylynamides with various functional groups and different substitution patterns can be converted into 3-aza-bicyclo[3.1.0]hexan-2-one derivatives in moderate to high yield using IMesAuCl/AgBF4 as the catalyst and pyridine N-oxide as the oxidant. A noncarbene mediated approach is proposed as the mechanism.
- Wang, Kai-Bing,Ran, Rui-Qiao,Xiu, Shi-Dong,Li, Chuan-Ying
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supporting information
p. 2374 - 2377
(2013/06/27)
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- Synthesis of isoprenoid chain-contained chemical probes for an investigation of molecular interactions by using quartz crystal microbalance
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Five probes including four that contained isoprenoid chain were synthesized. These probes were assembled onto the gold-coated quartz crystal chips for analysis of their interactions with four yeast proteins by using the quartz crystal microbalance technology. Results showed that 3-phosphoglycerate phosphokinase and triosephosphate isomerase had clear interactions with certain probes, while glutathione reductase and phosphoglucose isomerase gave much lower interaction signals. It also suggested that 3-phosphoglycerate phosphokinase had two sites interacting with the probe attached with a geranyl moiety. Further molecule simulation experiments provided supportive information on these intermolecular interactions. Together, our data suggested that there are hydrophobic interactions, with relatively good selectivity, between isoprenoid chain and proteins.
- Liu, Wujun,Zhang, Yixin,Hou, Shuhua,Zhao, Zongbao Kent
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supporting information
p. 6208 - 6210
(2013/10/22)
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- Lanosterol biosynthesis: The critical role of the methyl-29 group of 2,3-oxidosqualene for the correct folding of this substrate and for the construction of the five-membered D ring
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Lanosterol synthase catalyzes the polycyclization reaction of (3S)-2,3-oxidosqualene (1) into tetracyclic lanosterol 2 by folding 1 in a chair-boat-chair-chair conformation. 27-Nor- and 29-noroxidosqaulenes (7 and 8, respectively) were incubated with this enzyme to investigate the role of the methyl groups on 1 for the polycyclization cascade. Compound 7 afforded two enzymatic products, namely, 30-norlanosterol (12) and 26-normalabaricatriene (13; 12/13 9:1), which were produced through the normal chair-boat-chair-chair conformation and an atypical chair-chair-boat conformation, respectively. Compound 8 gave two products 14 and 15 (14/15 4:5), which were generated by the normal and the unusual polycyclization pathways through a chair-chair-boat-chair conformation, respectively. It is remarkable that the twist-boat structure for the B-ring formation was changed to an energetically favored chair structure for the generation of 15. Surprisingly, 14 and 15 consisted of a novel 6,6,6,6-fused tetracyclic ring system, thus differing from the 6,6,6,5-fused lanosterol skeleton. Together with previous results, we conclude that the methyl-29 group is critical to the correct folding of 1, with lesser contributions from the other branched methyl groups, such as methyl-26, -27, and -28. Furthermore, we demonstrate that the methyl-29 group has a crucial role in the formation of the five-membered D ring of the lanosterol scaffold. Ringing in the changes: The incubation of 1 with porcine-liver cyclase afforded new nortriterpenes 2 and 3 with 6,6,6,6-fused tetracyclic skeletons, which were produced by chair-boat-chair-chair and chair-chair-boat-chair conformations, respectively (see scheme), thus indicating that the 29-methyl group is critical to the correct folding of oxidosqualene and to the formation of the five-membered D ring for lanosterol biosynthesis. Copyright
- Hoshino, Tsutomu,Chiba, Akifumi,Abe, Naomi
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supporting information
p. 13108 - 13116
(2013/01/15)
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- Efficient organic transformations mediated by ZrOCl28H 2O in Water
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Operationally simple and environmentally benign methods for some organic transformations comprising reductive coupling of sulfonyl chlorides, chemoselective deoxygenation of sulfoxides, and halogenation of alcohols mediated by ZrOCl28H2O/MX in water have been developed.
- Jafarpour, Maasoumeh,Rezaeifard, Abdolreza,Heidari, Mahdieh
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experimental part
p. 1470 - 1482
(2011/10/05)
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- METHOD OF PRODUCING A POLYMERIC MATERIAL, POLYMER, MONOMERIC COMPOUND AND METHOD OF PREPARING A MONOMERIC COMPOUND
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A method of producing a polymeric material, said method including the step of subjecting a starting material which includes a group of sub-formula (XIII) where R16 is selected from hydrogen, halo, nitro, hydrocarbyl, optionally substituted or interposed with functional groups, or R2 and R3 are independently selected from (CR6R7)n or a group CR8R9, CR6R7CR8R9 or CR8R9CR6R7 where n is 0, 1 or 2, R6 and R7 are independently selected from hydrogen or alkyl, and either one of R8 or R9 is hydrogen and the other is an electron withdrawing group, or R8 or R9 together form an electron withdrawing group; and R4 and R5 are independently selected from CH or CR1o where CR1o is an electron withdrawing group, the dotted lines indicate the presence or absence of a bond, X1 is a group CX2X3 where the dotted line bond to which it is attached is absent and a group CX2 where the dotted line bond to which it is attached is present, Y1 is a group CY2Y3 where the dotted line bond to which it is attached is absent and a group CY2 where the dotted line bond to which it is attached is present, and X2 and X3, and, if present, Y2 and Y3, are each a C1 to C4 alkyl group; to conditions under which polymerisation of the starting material occurs.
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- Synthesis of (±)Abyssinone I and related compounds: Their anti-oxidant and cytotoxic activities
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An efficient and facile synthesis of naturally occurring prenylated flavonoids and their analogs have been described. Abyssinone I (9a) was prepared by condensing 2,2-dimethyl chrom-3-en-6-carboxaldehyde (5a) with protected resacetophenone under phase transfer conditions followed by deprotection and cyclization. The influence of prenyl group on anti-oxidant and cytotoxic activities was studied. The presence of 3′-prenyl group as in 8c enhanced radical scavenging activity but decreased reducing power activity when compared to non-prenylated analog 8f. In vitro testing in MCF-7 cell line revealed that prenylated chalcones and flavanones showed better inhibitory activity than their non-prenylated counterparts. Abyssinone I and its chalcone though exhibited negligible anti-oxidant activity their cytotoxic activities were comparable with other prenylated analogs.
- Rao, Gudapati Venkateswara,Swamy, Badrappa Narayana,Chandregowda, Venkateshappa,Reddy, G. Chandrasekara
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experimental part
p. 2239 - 2245
(2009/09/08)
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- A novel one-pot conversion of allyl alcohols into primary allyl halides mediated by acetyl halide
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A new and simple method for the synthesis of the primary allyl chlorides and bromides 9-16 from the secondary or tertiary allyl alcohols 3-8 and acyl halide was developed (Scheme 2, Table 1). Non-commercially available secondary and tertiary allyl alcohols were synthesized from the related ketones and aldehydes via the addition of vinylmagnesium chloride. Mechanistic studies indicate that the alcohols were first acetylated by the acetyl halide and then protonated prior to substitution by the halide, Cl- or Br -, via an 5N2′ reaction, to yield the primary halides (Scheme 5).
- Kishali, Nurhan,Polat, M. Fatih,Altundas, Ramazan,Kara, Yunus
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- New efficient synthesis of ubiquinones
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A strategy for the ecofriendly and high-yielding synthesis of ubiquinones starting from simple materials and using mild conditions is reported. CoQ1, CoQ2, CoQ3, and CoQ9 were prepared. Copyright Taylor & Francis Group, LLC.
- Bovicelli, Paolo,Borioni, Giorgio,Fabbrini, Danilo,Barontini, Maurizio
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p. 391 - 400
(2008/04/01)
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- Radical-scavenging polyphenols: New strategies for their synthesis
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New strategies for the synthesis of polyphenols, compounds with antioxidant properties contained in every kind of plants, are discussed. Syntheses of different classes of polyphenols, namely ubiquinones, present in many natural systems in which electron-transfer mechanisms are involved, hydroxytyrosol, one of the main components of the phenol fraction in olives, and flavonoids, widespread in the plant kingdom, were approached by simple and environmentally sustainable methods.
- Bovicelli, Paolo
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p. 1703 - 1710
(2008/03/11)
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- Phosphonates useful as modulators of t γ(g)9γ(d)2 lymphocyte activity
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The invention concerns novel phosphonate derivatives, preparation method, use thereof as ligands modulating T γ9δ2 lymphocyte activity and pharmaceutical compositions comprising them.
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Page/Page column 26
(2010/11/24)
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- Design, synthesis and biological evaluation of novel riccardiphenol analogs
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A novel, facile, high yield, and less cumbersome synthesis of riccardiphenol analogs is described. The synthesized compounds were characterized and assessed for its in vitro activity in a panel of human cancer cell lines of differing origin: HuCCT-1, BxPC3, Panc-1, Mia-Paca, A431, Hep2, and HN006. HuCCT-1 was derived from an intrahepatic cholangiocarcinoma; BxPC3, Mia-Paca, and Panc-1 were derived from pancreatic cancers; A431 was derived from a vulvar epithelial carcinoma; and Hep2 and HN006 were derived from squamous cell carcinomas of the head and neck. The cytotoxicity of a newly developed riccardiphenol analog against human cancer cell lines was assessed. The cancer cells exhibited varying sensitivities to the compound, with IC50 values from 30 to 50 μM. This susceptibility was particularly interesting in the case of lines such as Hep2 and BxPC3 that are resistant to classic cytotoxic drugs as well as some targeted agents. These results demonstrate that the novel riccardiphenol analog has effective action against human-derived cancer cell in vitro.
- Kumar, Srinivas K.,Amador, Maria,Hidalgo, Manuel,Bhat, Sujata V.,Khan, Saeed R.
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p. 2873 - 2880
(2007/10/03)
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- Studies on taxadiene synthase: Interception of the cyclization cascade at the isocembrene stage with GGPP analogues
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The cyclization of GGPP to taxadiene, catalyzed by taxadiene synthase, has been suggested to proceed through a series of monocyclic isocembrenyl- and bicyclic verticillyl-carbocationic intermediary stages. A set of GGPP analogues with abolished or perturbed π-nucleophilicity at the Δ10 double bond (GGPP numbering) was synthesized and incubated with taxadiene synthase to intercept the cyclization cascade at the monocyclic stage. Each analogue was transformed by taxadiene synthase in vitro to hydrocarbon products in varying yields, and the structures of the major product in each reaction were solved by GCEIMS and one- and two-dimensional (1H and 13C) NMR and found to be 14-membered monocyclic isocembrenyl diterpenes, indicating that the first C-C bond formation catalyzed by taxadiene synthase could be uncoupled from the other subsequent bond formation events by using suitably designed substrate analogues. The formation and isolation of these isocembrenyl diterpene products using taxadiene synthase supports proposals that the isocembrenyl cation is an intermediate in the cyclization of GGPP to taxadiene.
- Chow, Siew Yin,Williams, Howard J.,Huang, Qiulong,Nanda, Samik,Scott, A. Ian
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p. 9997 - 10003
(2007/10/03)
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- Synthesis of prenyl pyrophosphonates as new potent phosphoantigens inducing selective activation of human Vγ9Vδ2 T lymphocytes
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γ9δ2T cells represent the most abundant population of human blood γδT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus- containing antigens in the family of prenyl pyrophosphates and their related biosynthetic precursors such as isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are naturally occurring metabolites in mycobacteria and several other microbial pathogens. The broad specificity in the recognition of these molecules by the T-lymphocyte population expressing a Vγ9Vδ2 cell receptor might facilitate their manipulation by designing small potent synthetic agonist ligands. In this paper, we describe the synthesis and the biological evaluation of new pyrophosphonate compounds as new isosteric analogues of natural prenyl pyrophosphates. Several prenyl and alkenyl pyrophosphonate with different chain lengths and degrees of insaturation (24-28, 48-50, and 64-66) were tested as well as the alkoxymethylpyrophosphonic analogue of IPP (compound 76) as its closest isostere. Several of them appeared to be better activators of Vγ9Vδ2 T cell proliferation than IPP. These results open the perspective of a potential use of isoprenoides pyrophosphonates as specific immunoregulatory molecules.
- Zgani, Ibrahim,Menut, Chantal,Seman, Michel,Gallois, Valerie,Laffont, Virginie,Liautard, Jeanine,Liautard, Jean-Pierre,Criton, Marc,Montero, Jean-Louis
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p. 4600 - 4612
(2007/10/03)
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- Squalene-hopene cyclase: Insight into the role of the methyl group on the squalene backbone upon the polycyclization cascade. Enzymatic cyclization products of squalene analogs lacking a 26-methyl group and possessing a methyl group at C(7) or C(11)
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To provide deep insight into the polycyclization reaction of squalene, some analogs were synthesized and incubated with the cell-free homogenates of the recombinant Escherichia coli encoding the wild-type squalene cyclase. The presence of C(6)-Me leads to an efficient polycyclization cascade. Substitution of the C(14)-H and the C(18)-H with a methyl group halted the polycylization reaction at the tricyclic ring stage having a 6/6/6-fused ring system and the tetracycle with a 6/6/6/6-fused ring, respectively, both of which were produced according to a Markovnikov closure. Replacement of the C(7)-H and the C(11)-H with a methyl group led to no cyclization. These results, in conjunction with our previous reports, indicated that the methyl positions are important for bringing to completion of the normal polycylization reaction and further demonstrated that the precise steric bulk size at the methyl positions of squalene is critical to the correct folding and the strong binding of the substrate to the squalene cyclase.
- Nakano, Shin-Ichi,Ohashi, Shumi,Hoshino, Tsutomu
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p. 2012 - 2022
(2007/10/03)
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- Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20 and C25 by recombinant squalene cyclase
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The substrate specificity of squalene-hopene cyclase was investigated using the C10-C25 analogs including naturally occurring substances, e.g. geraniol (C10), farnesol (C15) and geranylgeraniol (C20). No cyclization occurred for geraniol, but a significantly high conversion ratio (64%) was observed for farnesol, yielding the cyclic sesquiterpenes consisting of 6/6-fused bicyclic ring systems. Among them, an attractive compound having C30 was produced, in the structure of which acyclic the farnesol unit is linked to the bicyclic skeleton through ether linkage. Conversion of geranylgeraniol was low (ca. 12%). The squalene analogs having C20 and C25 also were cyclized in yields of ca. 33-36%, but the analogs having the methyl group at C(7) and/or at C(11) underwent no cyclization; the large steric bulk size of C(7)-Me and/or C(11)-Me, which is arranged in α-disposition for all the pre-chair conformation, would have interacted repulsively with the cyclase recognition site near to the C(7) and/or C(11), resulting in no construction of the all-chair conformation inside the reaction cavity. A relatively low yield of geranylgeraniol indicated that a less bulky hydrogen atom must be located at C(14) for the efficient polycyclization reaction. The squalene cyclase shows remarkably broad substrate specificity to accept the truncated analogs having carbon-chain lengths of C15-C25 in addition to C 30.
- Hoshino, Tsutomu,Kumai, Yuko,Kudo, Isao,Nakano, Shin-Ichi,Ohashi, Shumi
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p. 2650 - 2657
(2007/10/03)
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- Surface-mediated hydrohalogenation of isoprene: A facile preparation of prenyl halides
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The reaction of isoprene with SOCl2 (0.5 mol equiv.) or PBr3 (0.4 mol equiv.) or PI3 (0.4 mol equiv.) in the presence of SiO2 at -10°C produced prenyl chloride (82%), or bromide (70%) or iodide (65%), respectively, in less than 30 min reaction time.
- De Mattos, Marcio C. S.,Sanseverino, Antonio Manzolillo
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p. 2181 - 2186
(2007/10/03)
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- Preparation of [1,2,3,4,5-13C 5]-5-Amino-4-oxopentanoic Acid (ALA) - Design of a Synthetic Scheme to Prepare Any 13C- and 15N-Isotopomer with High Isotopic Enrichment
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5-Amino-4-oxopentanoic acid (5-aminolevulinic acid) is a precursor in the biosynthesis of the biologically active porphyrins such as chlorophyll, bacteriochlorophyll, heme, etc. These systems are central in photosynthesis, oxygen transport, electron transport, etc. In this paper we describe a simple scheme to prepare any isotopomer of 5-aminolevulinic acid in a few steps in high yield. Using a similar scheme, levulinic acid can now also be prepared in any isotopomeric form. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Shrestha-Dawadi, Prativa Bade,Lugtenburg, Johan
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p. 4654 - 4663
(2007/10/03)
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- Synthesis of β-ionone
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Preparation of β-ionone by a reaction sequence starting from acetone is described.
- Vani,Chida,Srinivasan,Chandrasekharam,Singh
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p. 219 - 224
(2007/10/03)
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- First total synthesis of (±)-13-hydroxyneocembrene
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First total synthesis of (±)-13-hydroxyneocembrene (1), starting from 6-methyl-5-hepten-2-one (6) and geraniol (7), is described. The key steps are (i) the addition of sulfur-stabilized carbanion 12 to aldehyde 9, (ii) the synthesis of 18 by using phase-transfer catalyzed coupling reaction, and (iii) low-valent titanium-induced intramolecular coupling of oxo aldehyde 3 to afford the target molecule after the final deprotection.
- Xing, Yacheng
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p. 595 - 600
(2007/10/03)
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- The Heterogeneous Catalytic Hydrogenation of Cumulated Allene-cyclopropanes: 1-(2'-Methylpropenylidene)-7-bicycloheptane
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The formation of products from the heterogeneous solution phase catalytic hydrogenation of the title compound 1 in methanol over supported platinum and palladium catalysts has been studied using 'snapshot analysis' graphs. As expected from 'catalyst hindrance' considerations, the major first formed product with both metals is the conjugated cis-olefin-cyclopropane 7, the trans-isomer 8 being made for comparison by sodium in liquid ammonia reduction. Products appear and disappear during the hydrogenations leaving, at the cassation of reaction in the case of platinum catalyst, 75 percent of cyclopropane 6 and 25 percent of saturated hydrocarbon 3. Use of a palladium reverses the quantitative situation - 12 percent cyclopropane 6 and 88 percent of hydrocarbon 3. If in the title allene-cyclopropane structure 1 a methyl is inserted at position 1 of the cyclopropyl as in 13, complete hydrogenation over a palladium catalyst occurs with cleavage of the cyclopropane from the less hindered side forming a quaternary centre 14 in high yield. Catalytic hydrogenation of a related conjugated diene having one double bond cumulated with a cyclopropane ring 12 is also considered. Dimethylallene carbene reacts selectively towards an (E)-linkage of (Z)-(E)-(E)-cyclododeca-1,5,9-triene giving 19 as the crystalline product.
- Cromble, Leslie,Fernando, Candida E. C.
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p. 1501 - 1518
(2007/10/03)
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- Esterification of carboxylic acid salts
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Mono- or polycarboxylic acid esters are prepared by reacting a salt of such carboxylic acid with an organic halocompound, e.g., a (cyclo)alkyl, (cyclo)alkenyl, aryl or aralkyl halide, in an aqueous reaction medium, in the presence of a catalytically effective amount of a phase transfer catalyst, for example an onium salt.
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- Indole derivatives as 5-HT1-like agonists
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Compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 is a substituted alkylene; C3 -C7 cycloalkyl optionally substituted with HO; C3 -C6 alkenyl optionally substituted with aryl; C5 -C7 cycloalkenyl; or C3 -C6 alkynyl; R2 is H; halo; F3 C; NC; R8 R9 NOC; a substituted alkylene; R8 R9 NO2 S; R10 S(O)m ; R12 CON(R11); R10 SO2 N(R11); R8 R9 NOCN(R11); R10 O2 CN(R11); R13 (CH2)n CH=CH; or R7 O are selective 5-HT1 -like receptor agonists useful in the treatment of migraine, cluster headache, chronic paroxysmal hemicrania and headache associated with vascular disorders.
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- Marine Alkaloids. 17. Synthesis of (+/-)-Debromoflustramide B and E and (+/-)-Debromoflustramine B and E
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(+/-)-Debromoflustramide B, (+/-)-debromoflustramine B, (+/-)-debromoflustramide E and (+/-)-debromoflustramine E have been synthesized and characterized.In addition a dimer of (+/-)-debromoflustramide B, 1,1'-dimethyl-3a,3a'-di(3-methylbut-2-enyl)-8,8'-(3,3,4,4-tetramethylhexa-1,5-dienylidene)bisindol-2(1H)-one> has been isolated and characterized.The spectroscopic properties are reported for all compounds.
- Jensen, Jan,Anthoni, Uffe,Christophersen, Carsten,Nielsen, Per H.
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- A regioselective synthesis of 3-isoprenyl-4-hydroxycoumarins
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The dianion of ethyl 3-(2-hydroxyphenyl)-3-oxopropanoate can be regioselectively alkylated with isoprenyl bromides to give, after hydrolytic work-up, the corresponding 3-substituted-4-hydroxycoumarins.
- Appendino,Cravotto,Nano,Palmisano
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p. 2205 - 2212
(2007/10/02)
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- Thiochroman esters of phenols and terephthallates having retinoid-like activity
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Compounds of formula I STR1 in which: the R groups are independently hydrogen or lower alkyl; one of A and B is O or S and the other is --C(O)--, A being attached to the thiochroman ring at the 6 or 7-position;n is 0-5; andZ is H, an acid or acid derivative, an alcohol or alcohol derivative, acetal or acetal derivative or ketone or ketone derivative, or a pharmaceutically acceptable salt, have retinoid-like activity.
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- Phosphorylation of Isoprenoid Alcohols
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Procedures for the synthesis and purification of 20 isoprenoid diphosphates and methanediphosphonate analogues from the corresponding alcohols are described.The alcohols are activated for phosphorylation by conversion of homoallylic systems to tosylates and allylic systems to halides.The activated intermediates are treated with tris(tetra-n-butylammonium) salts of pyrophosphoric, methanediphosphonic, or difluoromethanediphosphonic acid to obtain the corresponding esters in yields 34-80percent.Chromatography on cellulose is a general method for purification of isoprenoid diphosphates, and procedures are decribed for compounds with C5 to C20 hydrocarbon moieties.The displacement by pyrophosphate occurs with inversion of configuration, and the procedure can be used to prepare isoprenoid diphosphates with chiral C1 methylene groups in high optical purity from the corresponding alcohols.
- Davisson, V. Jo,Woodside, Andrew B.,Neal, Timothy R.,Stremler, Kay E.,Muehlbacher, Manfred,Poulter, C. Dale
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p. 4768 - 4779
(2007/10/02)
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- The Stereocontrolled Horner-Wittig Reaction: Synthesis of Disubstituted Alkenes
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Addition of the lithium derivatives of phosphine oxides Ph2P(O)CH2R1 to aldehydes gives erythro adducts (11) with good stereoselectivity.Reduction of α-diphenylphosphinoyl ketones (12) gives threo adducts (11) with even better stereoselectivity.Purification by flash chromatography and/or crystallisation followed by elimination of Ph2PO2 gives pure Z- or E-alkenes with high material conversion.Explanations are offered for the stereoselectivities, conditions defined for full stereochemical control, and guidelines suggested for approaches to a given alkene.
- Buss, Antony D.,Warren, Stuart
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p. 2307 - 2326
(2007/10/02)
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- Stereospecific, R2AlCl-Promoted Intramolecular Ene Reaction of a 1,6-Dienoate: Evidence for a Concerted Mechanism
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Treatment of the 83percent-trans-13CH3-labelled 1,6-dienoate 7 with Et2AlCl at -78 deg C provided in high yield the ene product 9 containing 83percent 13C localized in the olefinic C(8)-methylene group.Accordingly, H-transfer occurs exclusively from the trans-methyl group of 7, consistent with a concerted ene process 7->9 thereby ruling out an intermediate cation 8 (Scheme 4).
- Oppolzer, Wolfgang,Mirza, Sohail
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p. 730 - 738
(2007/10/02)
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- THE SYNTHESIS OF C-13 LABELED VITAMIN E, all-rac-α-TOCOPHEROL
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Vitamin E with a 13C-labeled isoprenoid side chain, all-rac-=α-tocopherol (1), was synthesized using 6-methoxymethoxy-2,5,7,8-tetramethyl-2-(5-mercaptothiazolinyl-4-methyl-3-penten-1-yl)chroman (8) as a key intermediate and methyl iodide as a 13C source.The total yield of the labeled tocopherol based on methyl iodide was 51.2percent.
- Urano, Shiro,Tokuzawa, Kumiko,Nakano, Shun-Ichiro,Matsuo, Mitsuyoshi
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p. 257 - 260
(2007/10/02)
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