- Preparation of (2R,4S)/(2S,4S)-4-hydroxypipecolinic acid derivatives from L-(-)-malic acid
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Synthetically important 4-hydroxypipecolinic acid derivatives were efficiently prepared from commercially available L-(-)-malic acid. The stereochemistries of the derivatives synthesized by our method were determined by coupling constant analyses with key methine protons on C2 and C4.
- Yin, Shuqiang,Taneda, Hiroshi,Li, Bozhi,Zhou, Dejun,Minato, Daishiro,Sugimoto, Kenji,Matsuya, Yuji
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- Synthesis of a Cn-Cn+6 building block common to important polyol,polyene antibiotics from a divinylcarbinol by a desymmetrizing sharpless epoxidation
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A stereocontrolled synthesis of the enantiomerically pure epoxide 7b from propargyl ether 15 has been realized in 15 steps. Epoxide 7b represents a building block for the "eastern" moieties of the title compounds. Key steps in our approach were a desymmetrizing Sharpless epoxidation (→a€‰anti,cis-16), the selective processing of the bis-enolate of the bis(tert-butyl alkoxyacetate) 11 through a diastereoselective [2,3]-Wittig rearrangement (→a€‰syn,syn-9), and a stereo- and chemoselective iodolactonization (→a€‰35). The CO2H groups of dicarboxylic acid 37 were differentiated in a one-pot bis-oxidation reaction. The latter entailed the novel transformation of HO2CCH2-O-alkyl into AcOCH2-O-alkyl. The termini of a bis(tert-butyl alkoxyacetate) have been differentiated by forming the bis-enolate and engaging one enolate in a diastereoselective [2,3]-Wittig rearrangement. A diastereo- and chemoselective iodolactonization established the stereocenter of the epoxide ring. Copyright
- Nachbauer, Luc,Brueckner, Reinhard
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- Transacetalization of acetals with butane-1,2,4-triol using cobalt(II) chloride and chlorotrimethylsilane
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Transacetalization of acetals with butane-1,2,4-triol was carried out using cobalt(II) chloride and chlorotrimethylsilane as catalysts. The reaction occurs under mild conditions in acetonitrile and with a short reaction time. The synergic effect of the two Lewis acids catalyzes the conversion of butane-1,2,4-triol into (2-alkyl- or 2-aryl-1,3-dioxan-4-yl)methanol derivatives with high regiospecificity and diasteroselectivity. Georg Thieme Verlag Stuttgart · New York.
- Battisti, Umberto Maria,Sorbi, Claudia,Franchini, Silvia,Tait, Annalisa,Brasili, Livio
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- Biochemistry-Guided Prediction of the Absolute Configuration of Fungal Reduced Polyketides
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Highly reducing polyketide synthases (HR-PKSs) produce structurally diverse polyketides (PKs). The PK diversity is constructed by a variety of factors, including the β-keto processing, chain length, methylation pattern, and relative and absolute configurations of the substituents. We examined the stereochemical course of the PK processing for the synthesis of polyhydroxy PKs such as phialotides, phomenoic acid, and ACR-toxin. Heterologous expression of a HR-PKS gene, a trans-acting enoylreductase gene, and a truncated non-ribosomal peptide synthetase gene resulted in the formation of a linear PK with multiple stereogenic centers. The absolute configurations of the stereogenic centers were determined by chemical degradation followed by comparison of the degradation products with synthetic standards. A stereochemical rule was proposed to explain the absolute configurations of other reduced PKs and highlights an error in the absolute configurations of a reported structure. The present work demonstrates that focused functional analysis of functionally related HR-PKSs leads to a better understanding of the stereochemical course.
- Akimitsu, Kazuya,Guo, Yian,Hashimoto, Masaru,Kotani, Akari,Minami, Atsushi,Mochizuki, Susumu,Oikawa, Hideaki,Ozaki, Taro,Peng, Wenquan,Takino, Junya,Ye, Tao,Yu, Jie
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supporting information
p. 23403 - 23411
(2021/09/18)
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- Total Synthesis and Biological Evaluation of Siladenoserinol A and its Analogues
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The total synthesis of siladenoserinol A, an inhibitor of the p53–Hdm2 interaction, has been achieved. AuCl3-catalyzed hydroalkoxylation of an alkynoate derivative smoothly and regioselectively proceeded to afford a bicycloketal in excellent yield. A glycerophosphocholine moiety was successfully introduced through the Horner–Wadsworth–Emmons reaction using an originally developed phosphonoacetate derivative. Finally, removal of the acid-labile protecting groups, followed by regioselective sulfamate formation of the serinol moiety afforded the desired siladenoserinol A, and benzoyl and desulfamated analogues were also successfully synthesized. Biological evaluation showed that the sulfamate is essential for biological activity, and modification of the acyl group on the bicycloketal can improve the inhibitory activity against the p53–Hdm2 interaction.
- Yoshida, Masahito,Saito, Koya,Kato, Hikaru,Tsukamoto, Sachiko,Doi, Takayuki
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supporting information
p. 5147 - 5150
(2018/03/26)
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- Improved synthesis of C8-C20 segment of pectenotoxin-2
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The C8-C20 segment of pectenotoxin-2 was efficiently synthesized in 16% overall yield in 22 steps from l-malic acid via an improved route.
- Fujiwara, Kenshu,Suzuki, Yuki,Koseki, Nao,Murata, Shun-Ichi,Murai, Akio,Kawai, Hidetoshi,Suzuki, Takanori
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scheme or table
p. 5589 - 5592
(2011/11/07)
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- A new synthetic strategy for 2-deoxy-D-ribose via palladium(II)-catalyzed cyclization of aldehyde
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We achieved a total synthesis of 2-deoxy-D-ribose through intramolecular Pd(II)-catalyzed cyclization of aldehyde via an unstable hemiacetal intermediate as a key step. The Japan Institute of Heterocyclic Chemistry.
- Miyazawa, Masahiro,Awasaguchi, Ken-Ichiro,Uoya, Ikuyo,Yokoyama, Hajime,Hirai, Yoshiro
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experimental part
p. 1891 - 1902
(2011/04/12)
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- New and concise approach to (R)-α-lipoic acid
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A concise enantiospecific synthesis of (S)-6,8-bis(methylsulfonyloxy)- octanoic acid (2), a ready precursor of (R)-(+)-α-lipoic acid (1), is reported. The key step of the synthesis is the coupling of the tosylate derived from (R)-malic acid with phenylpro
- Wei, Zhen,Lan, Hong-Qiao,Zheng, Jian-Feng,Huang, Pei-Qiang
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experimental part
p. 691 - 701
(2009/07/18)
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- Third-generation immucillins: Syntheses and bioactivities of acyclic immucillin inhibitors of human purine nucleoside phosphorylase
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ImmH (1) and DADMe-ImmH (2) are potent inhibitors of human purine nucleoside phoshorylase (PNP), developed by us and currently in clinical trials for the treatment of a variety of T-cell related diseases. Compounds 1 and 2 were used as templates for the design and synthesis of a series of acyclic immucillin analogues (8-38) in order to identify simplified alternatives to 1 and 2. SerMe-ImmG (8) and DATMe- ImmG (9) displayed the lowest inhibition constants of 2.1 and 3.4 pM, respectively, vs PNP. It was postulated that the flexible natures of 8 and 9 enabled them to adopt conformations resembling those of 1 and 2 within the active site of PNP and that the positioning of two hydroxyl groups was critical for picomolar activity. SerMe-ImmH (10, K d = 5.2 pM) was shown to be orally available in mice with a long biological residence time on blood PNP.
- Clinch, Keith,Evans, Gary B.,Frohlich, Richard F. G.,Furneaux, Richard H.,Kelly, Peter M.,Legentil, Laurent,Murkin, Andrew S.,Li, Lei,Schramm, Vern L.,Tyler, Peter C.,Woolhouse, Anthony D.
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experimental part
p. 1126 - 1143
(2010/02/16)
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- Stereoselective total synthesis of the nonenolide (+)-microcarpalide
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The enantiomer [(+)-1] of the nonenolide natural product microcarpalide [(-)-1] has been prepared from (S)-malic acid (3) and 3-decyn-1-ol (11) via a sixteen step sequence involving, inter alia, two metathesis processes.
- Banwell, Martin G.,Loong, David T. J.
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p. 713 - 734
(2007/10/03)
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- A stereoselective and short total synthesis of the polyhydroxylated γ-amino acid (-)-detoxinine, based on stereoselective preparation of dihydropyrrole derivatives from lithiated alkoxyallenes
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Based on our earlier results employing lithiated methoxyallene 2 as C3 building block and imines 3 for the synthesis of dihydropyrrole derivatives 5, we have investigated chiral imines 6, 10, and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydropyrrole derivatives 8, 12, 17, 20, and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of achelate control. Treatment with hydrochloric acid converted syn-8 and syn-12 into bicyclic compounds 9 and 13, whereas under more mildly acidic conditions adduct syn-17 was transformed into diol syn-18. The total synthesis of the uncommon γ-amino acid (-)-detoxinine could be achieved by starting from (S)-malic acid, which was converted into imine 15 in four steps. Lithiated benzyloxyallene added to imine 15 and efficiently furnished the crucial dihydropyrrole derivative syn-22. The hydrogenolysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29, which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (-)-detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be performed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds.
- Floegel, Oliver,Amombo, Marlyse Ghislaine Okala,Reissig, Hans-Ulrich,Zahn, Gernot,Bruedgam, Irene,Hartl, Hans
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p. 1405 - 1415
(2007/10/03)
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- Enantiocontrolled synthesis of trialkyl-substituted stereogenic carbons. A general route to cis-3,5-dialkyl γ-lactones
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(Formula Presented) Lewis acid treatment of tertiary Co2(CO)6-propargylic alcohols having a stereochemically defined benzyloxy group at the γ-benzyl position yielded after cobalt demetalation sec-dialkyl bishomopropargylic alcohols in good yields. The reaction is highly stereoselective and predictable, providing pure stereoisomers. The use of benzyl-α,α′-d2 ethers permitted the stereoselective d-labeling of methines and methylenes. Very simple chemical manipulations provided a general methodology to obtain the enantiomers of 3,5-dialkyl-γ-lactones.
- Díaz, David,Martín, Víctor S.
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p. 335 - 337
(2007/10/03)
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- Towards the diastereoselective functionalization of non-racemic acetal derivatives of η6-arylcarbonyl complexes of tricarbonylchromium
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(S)-Butane-1,2,4-triol (2) has been investigated as a potential chiral auxiliary for the formation of non-racemic acetals derived from η6-arylcarbonyl complexes of tricarbonylchromium. Predominantly the cis dioxan (5) was formed from benzaldehyde, leading to preparation of the η6-Cr(CO)3 complex (16), and of the derived complexes (23) and (24). Lithiation-electrophile quenching of these complexes gave a mixture of products arising from ortho and benzylic functionalization. Reaction of acetophenone, or of the η6-Cr(CO)3 complexes (45) or (46), with either the triol (2) or its tris(silyl) ether (15) under conditions of kinetic or thermodynamic control gave an inseparable mixture of acetals.
- Kendall, Jackie D.,Woodgate, Paul D.
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p. 1083 - 1096
(2007/10/03)
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- An enantiocontrolled synthesis of pyrrolizidines, (-)-platynecine and (-)-hadinecine
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Trisubstituted allylic alcohols 13 and 14 have been converted into a single isomeric trans-oxazoline 16 via an intramolecular iodoamidation of the corresponding trichloroacetimidates, which have been elaborated into (-)-platynecine 1 and(-)-hadinecine 2 via a common intermediate pyrrolizidine.
- Kang, Sung Ho,Kim, Geun Tae,Yoo, Yong Sang
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p. 603 - 606
(2007/10/03)
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- A new chiral synthesis of bullfrog bile sterol 5β-ranol
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(24R)-27-Nor-5β-cholestane-3α,7α,12α,24,26-pentol (5β-ranol) has been synthesised by the Wittig olefinic coupling of a steroidal module and a side-chain module followed by reduction and deprotection. The steroidal module is derived from cholic acid by a one-carbon degradation of the side chain to produce norcholic acid followed by the loss of a second carbon in an iododecarboxylation and then synthesis of the triphenylphosphonium iodide. The side-chain module is derived from (S)-(-)-butane-1,2,4-triol by benzylidene protection of the 2,4-diol followed by Swern oxidation to the aldehyde. This general synthetic scheme could be used to produce a range of bile sterols with the (24R)-hydroxy moiety which may have significant hepatoprotective activity against liver damage induced by free radicals or reactive metabolites.
- Harney, Don W.,Macrides, Theodore A.
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p. 1353 - 1356
(2007/10/03)
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- Stereoselective syntheses and reactions of chiral oxygenated α,β-unsaturated-γ- and δ-lactones
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The syntheses of the chiral α,β-unsaturated lactones (+)-5, (-)-6, (+)-8, (+)-9, and (+)-10 have been efficiently achieved from readily available starting materials. The lactone (+)-5 has been synthesized in 7 steps from (R,R)-dimethyl tartrate (38-43% overall yield). The use of (+)-5 in formal syntheses of natural (+)-asperlin 4 and advanced intermediates for (+)-olguine 2 are also reported. The lactone (-)-6 has been prepared in 5 steps from (R)-malic and (44-50% overall yield). It can be a useful precursor for the syntheses of branched chain and deoxy nucleoside analogues. The preparation of (-)-6 constitutes formal syntheses of natural (+)-eldanolide 53 and the (+)-Geissman-Waiss lactone 54 (an intermediate for the syntheses of a variety of pyrrolizidine alkaloids). The lactones (+)-8, (+)-9 and (+)-10 have been synthesized from 3,4-di-O-acetyl-L-rhamnal 58. The highly diastereoselective transformations of (+)-9 and (+)-10, through sequential conjugate nucleophilic addition and enolate reaction, into densely functionalized chiral γ-lactones 12 are also reported. Copyright (C) Elsevier Science Ltd.
- Sanchez-Sancho, Francisco,Valverde, Serafin,Herradon, Bernardo
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p. 3209 - 3246
(2007/10/03)
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- Biocatalytic synthesis of chiral polyoxygenated compounds: Modulation of the selectivity upon changes in the experimental conditions
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Derivatives of both enantiomers of butane-1,2,4-triol have been obtained through a transesterification reaction catalyzed by Pseudomonas fluorescens lipase (PFL) in organic solvents. The influence of the solvent on the enantioselectivity has been thorough
- Herradon,Valverde
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p. 1479 - 1500
(2007/10/02)
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- Regio- and enantioselective esterifications of polyoxygenated compounds catalyzed by lipases
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The lipase catalyzed esterifications of derivatives of propane-1,2,3-triol and butane 1,2,4-triol in organic solvents have been studied. The influence of several factors (lipase source, organic solvent, additives and structural variations in the substrate
- Herradon,Cueto,Morcuende,Valverde
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p. 845 - 864
(2007/10/02)
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- Homochiral 2,4-Disubstituted 1,3-Dioxanes from (S)-(-)-Malic Acid: Stereoselective Synthesis and Investigation of the NMDA Receptor Affinity of All Four Stereoisomers
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Starting from a single enantiomerically pure compound, (S)-(-)-malic acid, all four stereoisomeric 4-dimethylaminomethyl-2-phenyl-1,3-dioxanes (S,S)-15, (R,R)-15 (S,R)-16, and (R,S)-16 are prepared: Transacetalisation of benzaldehyde dimethyl acetal (6b) with (S)-(-)-methyl 2,4-dihydroxybutyrate (7a), which is obtained by chemoselective BH3 reduction of (S)-(-)-malic acid monoester 8b, yields the diastereomeric 1,3-dioxane derivatives (S,S)-10 and (R,S)-11 in a 85:15 ratio.LDA deprotonation of (S,S)-10 followed by protonation leads to C-4 epimerisation .The thermodynamically controlled 88:12 equilibrium of (R,R)-10 and (S,R)-11 is reached by treatment of (S,R)-11 with acid.Aminolysis with dimethylamine and subsequent LiAlH4 reduction transform the four stereoisomeric esters (S,S)-10, (R,R)-10, (S,R)-11 and (R,S)-11 to give the amines (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16, respectively.In the 3H-(+)-MK 801 displacement experiment (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16 show a very little affinity to the phencyclidine binding site in the cation channel associated with the NMDA receptor. - Key Words: Butyric acid derivatives, (S)-(-)-24-dihydroxy-/ 1,3-Dioxanes/ NMDA antagonists, noncompetitive
- Wuensch, Bernhard,Diekmann, Heike,Hoefner, Georg
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p. 1273 - 1278
(2007/10/02)
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- Lipase catalyzed kinetic resolution of (±)-cis-4-hydroxymethyl-2-phenyl-1,3-dioxane
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The title compound has been kinetically resolved through a lipase catalyzed transesterification in organic solvents. The influence of the enzyme source, as well as the nature of the solvent on the enantioselectivity have been studied.
- Herradon
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p. 209 - 212
(2007/10/02)
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- EFFICIENT SYNTHESIS OF (R)-5-(2-HYDROXYETHYL)-2(5H)-FURANONE FROM (R)-MALIC ACID
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The title compound has been synthesized in five steps, 48percent overall yield, from (R)-malic acid.
- Herradon, Bernardo
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p. 191 - 194
(2007/10/02)
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- CHELATION AND NON-CHELATION DIRECTED CLEAVAGE OF ACETALS
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Regioselectivity in the cleavage of chiral 2-substituted-3-methoxymethyl-1,3-dioxanes can be controlled to a high degree by choice of an appropriate activating Lewis acid.However, the diastereoselectivity of the cleavage reactions is uniformely poor.
- Corcoran, Robert C.
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p. 2101 - 2104
(2007/10/02)
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- AN EFFICIENT AND STEREOCONTROLLED SYNTHESIS OF PLATELET ACTIVATING FACTOR FROM (S)-(-)-MALIC ACID
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A stereocontrolled synthesis of C16-PAF (11) from (S)-(-)-malic acid (1), employing regioselective hydrogenolytic cleavage of benzylidene acetal derivatives of (S)-1,2,4-butanetriol (2) with borane-tetrahydrofuran complex, is described.
- Tsuri, Tatsuo,Kamata, Susumu
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p. 5195 - 5198
(2007/10/02)
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