- Macrocyclisation of macrodiolide with dimethylaluminium methaneselenolate
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Dimethylaluminium methaneselenolate (Me2AlSeMe, 1) acts as an acyl transfer agent for esterification. In cases of direct macrolactonisation (n = 10-12), this selenium-aluminium complex preferentially creates symmetric macrodiolides rather than macrolides. The factors determining macrodilactonisation were investigated and applied toward the total synthesis of norpyrenophorin, which result in a macrodilactonisation yield of 64 %. Dimethylaluminium methaneselenolate (Me2AlSeMe, 1) acts as an acyl transferagent for esterification. In cases of direct macrolactonisation (n = 10-12), this selenium-aluminium complex preferentiallycreates symmetric macrodiolides rather than macrolides. The factors determining macrodilactonisation were investigated and applied toward the total synthesis of nor-pyrenophorine. Copyright
- Shen, Liu-Lan,Mun, Han-Seo,Jeong, Jin-Hyun
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Read Online
- THE FACILE SYNTHESIS OF A LARGE RING LACTONE BY ACID-CATALYSED CYCLISATION OF AN (Z)-ENE-DIYNE HYDROXY ACID PRECURSOR.
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A large ring lactone is obtained in good yield by acid catalysed cyclisation of the ο-hydroxy acid precursor.
- Guillerm, Danielle,Linstrumelle, Gerard
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Read Online
- A Polyketide Cyclase That Forms Medium-Ring Lactones
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Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.
- Gao, De-Wei,Jamieson, Cooper S.,Wang, Gaoqian,Yan, Yan,Zhou, Jiahai,Houk,Tang, Yi
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- Ynamide-Mediated Macrolactonization
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Macrolactonization represents a long-standing challenge for organic chemists. Herein, an ynamide-mediated macrolactonization of seco-acids with the assistance of an acid catalyst is described. Various macrolactones ranging in ring size from medium to large can be prepared by using this method. The notorious issues associated with conventional macrolactonization reactions, such as the racemization/epimerization of seco-acids containing an α-chirality center, and the E/Z isomerization of α,β-unsaturated seco-acids can be avoided using this method. In addition, the ynamide-mediated two-step macrolactonization reaction can be performed in a one-pot manner, thus offering a user-friendly protocol. Cyclodepsipeptides containing both amide and ester bonds can also be constructed using this method as the key step to facilitate the ring closure. The total synthesis of dehydroxy LI-F04a, which contains a cyclic hexadepsipeptide core, has been accomplished using this method.
- Wang, Xuewei,Yang, Ming,Zhao, Junfeng
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p. 5230 - 5235
(2020/05/27)
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- Preparation method of 11- andrographolide compound and caprolactone compound (by machine translation)
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To the method, cyclohexenone spiro-11 - peroxide is used as a raw material, a protic acid is used as a catalyst, fluorine alcohol is used as a solvent, and the reaction temperature is in a range of from 25 °C~60 °C about. The method has the advantages of high yield, low cost, convenience in operation, mild reaction conditions and the like, and is convenient for industrial application. (by machine translation)
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Paragraph 0046-0070; 0075-0078
(2019/11/28)
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- Macrolactonization of Alkynyl Alcohol through Rh(I)/Yb(III) Catalysis
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A catalytic macrolactonization through oxidative cyclization of alkynyl alcohol by synergistic transition-metal and Lewis-acid catalysis was developed. Because the alkynyl alcohol substrates involved in this method are different from the seco acids that are used in conventional macrolactonization methods, the current method provides a strategically distinct entry to macrolactones. In addition to the operational simplicity, this macrolactonization protocol proceeds at relatively high concentration, precluding the need for high dilution or slow addition procedures.
- Zhang, Wen-Wen,Gao, Tao-Tao,Xu, Li-Jin,Li, Bi-Jie
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supporting information
p. 6534 - 6538
(2018/10/20)
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- Polycyclic ketone monooxygenase from the thermophilic fungus Thermothelomyces thermophila: A structurally distinct biocatalyst for bulky substrates
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Regio- and stereoselective Baeyer-Villiger oxidations are difficult to achieve by classical chemical means, particularly when large, functionalized molecules are to be converted. Biocatalysis using flavin-containing Baeyer-Villiger monooxygenases (BVMOs) is a wellestablished tool to address these challenges, but known BVMOs have shortcomings in either stability or substrate selectivity. We characterized a novel BVMO from the thermophilic fungus Thermothelomyces thermophila, determined its three-dimensional structure, and demonstrated its use as a promising biocatalyst. This fungal enzyme displays excellent enantioselectivity, acts on various ketones, and is particularly active on polycyclic molecules. Most notably we observed that the enzyme can perform oxidations on both the A and D ring when converting steroids. These functional properties can be linked to unique structural features, which identify enzymes acting on bulky substrates as a distinct subgroup of the BVMO class.
- Fürst, Maximilian J.L.J.,Savino, Simone,Dudek, Hanna M.,Castellanos, J. Rúben Gómez,De Souza, Cora Gutiérrez,Rovida, Stefano,Fraaije, Marco W.,Mattevi, Andrea
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supporting information
p. 627 - 630
(2017/05/15)
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- A catalytic oxidation ring 12 alkone method of synthesizing ring twelve lactone
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The invention discloses a method for synthesizing cyclododecalactone by catalytic oxidation of cyclododecanone. Cyclododecalactone is synthesized by using a molybdenum-containing compound as a catalyst, cyclododecanone as a raw material, a hydrogen dioxide solution as an oxidizing agent and acetonitrile as a solvent, wherein the molybdenum-containing compound is any one selected from ammonium molybdate, sodium molybdate, sodium phosphomolybdate and molybdenum oxide. With the molybdenum-containing compound used as the catalyst, there is no waste acid treatment or strong acid corrosion, energy conservation and emission reduction are realized and safety is high; with cyclododecanone used as the raw material, no high-temperature reflux reaction is required, and economic benefit and environmental benefit are raised; and by applying the hydrogen dioxide solution as an oxidizing agent, cleanability and safety of an industrial preparation reactions are raised, and environmental pollution is reduced.
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Paragraph 0018; 0019
(2016/10/07)
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- A highly efficient macrolactonization method via ethoxyvinyl ester
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We present the highly efficient reaction procedure of the macrolactonization method via ethoxyvinyl esters (EVEs). The following procedure was performed: 1)The EVE was prepared from hydroxycarboxylic acid and ethoxyacetylene in the presence of the Ru catalyst [RuCl2(p-cymene)] 2 in acetone; 2) after filtration of the Ru catalyst through a short-neutral SiO2 pad and evaporation of acetone, the EVE formed was diluted in 1,2-dichloroethane (DCE) and the solution was slowly added by a syringe pump to the highly diluted DCE solution of pTsOH (10mol%) at 80°C. Varioussized lactones could be produced by the method described here. It is note worthy that the method can give 9- to 14-membered macrolactones in good yields. This macrolactonization method via EVEs is useful for acid-/base-sensitive substrates. Furthermore, it was found that EVE formation was possible without loosing activity of the Ru catalyst even for the compounds with nucleophilic amine functions. The characteristic feature of the method was exemplified by the reaction of the compound 14 with many functional groups.
- Ohba, Yusuke,Takatsuji, Mayuko,Nakahara, Kenji,Fujioka, Hiromichi,Kita, Yasuyuki
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experimental part
p. 3526 - 3537
(2009/12/31)
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- Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of ω-methylated lactones: Tuning polymerizations by ring size
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Novozym 435-catalyzed ring-opening of a range of ω-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes ≤7) to large lactones (ring sizes ≥8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).
- Van Buijtenen, Jeroen,Van As, Bart A. C.,Verbruggen, Marloes,Roumen, Luc,Vekemans, Jef A. J. M.,Pieterse, Koen,Hilbers, Peter A. J.,Hulshof, Lumbertus A.,Palmans, Anja R. A.,Meijer
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p. 7393 - 7398
(2008/02/08)
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- Efficient method for the lactonization of ω-hydroxycarboxylic acids with di-2-thienyl carbonate by the promotion of catalytic amounts of DMAP and Hf(OTf)4
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An efficient method for the synthesis of macrolides from ω-hydroxycarboxylic acids is established by using an equimolar amount of di-2-thienyl carbonate (2-DTC) and catalytic amounts of 4-(dimethylamino) pyridine (DMAP) and group 4 metal triflates such as hafnium(IV) trifluoromethanesulfonate (Hf(OTf)4). Copyright
- Oohashi, Yoshiaki,Fukumoto, Kentarou,Mukaiyama, Teruaki
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p. 710 - 711
(2007/10/03)
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- A new method for the synthesis of carboxylic esters and lactones with di-2-thienyl carbonate (2-DTC) by the promotion of DMAP and iodine
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The esterification of carboxylic acids with alcohols by using di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino) pyridine (DMAP) proceeded smoothly to afford the corresponding esters in good-to-high yields along with 2(5H)-thiophenone. This esterification was accelerated by the addition of an equimolar amount of iodine to afford the esters in higher yields within a shorter reaction time. Further, cyclization of ω-hydroxycarboxylic acids with an equimolar amount of 2-DTC in the presence of a catalytic amount of DMAP, followed by the addition of 1-4 equimolar amounts of iodine, afforded the corresponding lactones in good-to-high yields under mild conditions. This method was successfully employed in the synthesis of erythro-aleuritic acid lactone.
- Oohashi, Yoshiaki,Fukumoto, Kentarou,Mukaiyama, Teruaki
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p. 1508 - 1519
(2007/10/03)
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- A new method for the lactonization of ω-hydroxy carboxylic acids with Di-2-thienyl carbonate by the promotion of DMAP and iodine
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Successive reactions of ω-hydroxycarboxylic acids with an equimolar amount of di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) followed by an addition of 2-4 equimolar amounts of iodine afforded the corresponding lactones in good to high yields. Copyright
- Oohashi, Yoshiaki,Fukumoto, Kentarou,Mukaiyama, Teruaki
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- An acid-catalyzed macrolactonization protocol.
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[reaction: see text] An efficient macrolactonization protocol devoid of any base was developed derived from the use of vinyl esters in transesterification. Subjecting a hydroxy acid and ethoxyacetylene to 2 mol % [RuCl(2)(p-cymene)](2) in toluene followed by addition of camphorsulfonic acid or inverse addition provided macrolactones in good yields.
- Trost, Barry M,Chisholm, John D
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p. 3743 - 3745
(2007/10/03)
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- A new method for the polymer-supported synthesis of cyclic oligoesters for potential applications in macrocyclic lactone synthesis and combinatorial chemistry
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Attachment of ω-hydroxyalkanecarboxylic acids to Merrifield beads followed by treatment with a catalytic amount of di-n-butyltin oxide in chlorobenzene at 133 °C for 4-18 h brought about the formation of the corresponding cyclic oligomers (COs) as the mai
- Ruddick, Clare L.,Hodge, Philip,Cook, Anthony,McRiner, Andrew J.
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p. 629 - 637
(2007/10/03)
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- An improved and novel approach to macrolactonisation using di-tert-butyl dicarbonate
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A new, facile, mild and simple method for the synthesis of macrolides was achieved from ω- hydroxy acids using di-tertbutyl dicarbonate (Boc2O), a cheap and commercially available reagent. A wide range of substrates were tested and give good yield of lactones. The effect of various simple bases on the yield of the macrolactonisation reaction was also studied.
- Nagarajan,Satish Kumar,Venkateswara Rao
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p. 12349 - 12360
(2007/10/03)
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- New and efficient method for the preparation of medium-sized lactones from the corresponding ω-hydroxycarboxylic acids
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Medium-sized lactones are prepared in good yields on treating monomeric cyclic silyl siloxycarboxylates, prepared in situ from ω-hydroxycarboxylic acids and 1,2-bisdimethylsilylbenzene using RhCl(PPh3)3 catalyst, with an active catalyst of dimethylsilylbis(trifluoromethanesulfonate).
- Mukaiyama, Teruaki,Izumi, Jun,Shiina, Isamu
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p. 187 - 188
(2007/10/03)
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- Scandium trifluoromethanesulfonate as an extremely active Lewis acid catalyst in acylation of alcohols with acid anhydrides and mixed anhydrides
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Scandium trifluoromethanesulfonate (triflate), which is commercially available, is a practical and useful Lewis acid catalyst for acylation of alcohols with acid anhydrides or the esterification of alcohols by carboxylic acids in the presence of p-nitrobenzoic anhydrides. The remarkably high catalytic activity of scandium triflate can be used for assisting the acylation by acid anhydrides of not only primary alcohols but also sterically-hindered secondary or tertiary alcohols. The method presented is especially effective for selective macrolactonization of ω-hydroxy carboxylic acids.
- Ishihara, Kazuaki,Kubota, Manabu,Kurihara, Hideki,Yamamoto, Hisashi
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p. 4560 - 4567
(2007/10/03)
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- A Novel Method for the Preparation of Macrolides from ω-Hydroxycarboxylic Acids
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An efficient method for the synthesis of macrolides directly from ω-hydroxycarboxylic acids is established by using 4-(trifluoromethyl)benzoic anhydride and a catalytic amount of active titanium(IV) salts together with chlorotrimethylsilane under mild conditions.
- Shiina, Isamu,Mukaiyama, Teruaki
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p. 677 - 680
(2007/10/02)
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- A New Synthetic Method of Macrocyclic Lactones from ω-Iodoalkylacrylates
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When the photostimulated cyclization reaction of ω-iodoalkylacrylates was performed in the presence of metal hydride complexes such as sodium cyanoborohydride (NaBH3CN), sodium borohydride (NaBH4) and potassium borohydride (KBH4), the corresponding macrocyclic lactones were produced.The use of NaBH3CN led to the highest yield of lactones.
- Abe, Motoji,Hayashikoshi, Takaoki,Kurata, Takeo
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p. 1789 - 1792
(2007/10/02)
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- LACTONIZATION REACTIONS OF (Ω-CARBOXYALKYL)SULFONIUM SALTS
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The intramolecular cyclizations of sulfonium salts having an ω-carboxyalkyl group were investigated for the synthesis of five- to nine-membered lactones, and five- to seven-membered lactones were obtained in good yields from S-(ω-carboxyalkyl)thiolanium salts.The scope and limitations of the synthetic utility of the reaction are indicated by this study. Key words: Lactonization reactions; (ω-carboxyalkyl)diphenylsulfonium salts; S-(ω-carboxyalkyl)thiolanium salts; medium-sized lactones; large-sized lactones; sulfur-containing lactones.
- Nakamura, Takako,Matsuyama, Haruo,Takahashi, Masaya,Kamigata, Nobumasa
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- Lack of a "Cesium Effect" on Macrolactonization
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The lactonization of ω-bromoalkanoate ions, run in DMF under preparative conditions and in the presence of counterions, is exploited to show that those synthetic effects whose manifestations has led to the coinage of the term "cesium effect" are simply due to the operation of well-established, rate-decreasing ion-pairing phenomena upon the reactivity of anionic nucleophiles.No peculiarity emerges with cesium when compared with the other alkali-metal ions.
- Galli, Carlo,Mandolini, Luigi
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p. 3045 - 3047
(2007/10/02)
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- Lactones. 3. A comparison of the basicities of lactones and esters
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The basicity of lactones and esters toward triethyloxonium ion was studied via NMR spectroscopy. The equilibrium constants were and the order of decreasing basicity was found to be δ-valerolactone > γ-butyrelactone > diethyl carbonate > ethyl acetate > ethyl propionate. The rates of reaction were parallel to the equilibrium constants. The origin of the differences in basicity was via ab initio calculations of structures and energies of ions formed by adding H+ or CH3+ to methyl acetate. The calculated proton affinity of the Z ester rotamer agreed with the experimental data and was found to be considerably smaller than that for the E rotamer. The relative energies of the four ions that could be formed by adding a proton to methyl acetate were related to the orientation of the dipole components at oxygen. The methyl cation affinities of the methyl acetate conformers were found to parallel the proton affinities and gave the same preferred direction of addition. The proton affinity of valerolactone was calculated to be greater than that for butyrolactone in good accord with the experimental results.
- Wiberg, Kenneth B.,Waldron, Boy F.
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p. 7705 - 7709
(2007/10/02)
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- Lactones. 2. Enthalpies of hydrolysis, reduction, and formation of the C4-C13 monocyclic lactones. Strain energies and conformations
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The enthalpies of hydrolysis of the monocyclic lactones from γ-butyrolactone to tridecanolactone were determined calorimetrically, and the acyclic ethyl having the number of atoms were studied in the fashion. The enthalpies of reduction of the lactones to the corresponding α,ω-alkanediols with lithium triethylborohydride also were determined. The enthalpies of formation of the lactones and the ethyl esters were derived from these data. They were converted to values for the gas phase by measuring the enthalpies of vaporization of ethyl esters and of lactones. In the of γ-butyrolactone and δ-valerolactone, the enthalpies of formation were in good accord with the previously reported values determined via combustion calorimetry. The strain energies of the lactones were obtained via isodesmic reactions. Valerolactone had a strain energy of 11 kcal/mol, and the largest strain energy was found with octanolactone (13 kcal/mol). The conformations of γ-butyrolactone and δ-valerolactone were studied via MP2/6-31G* geometry optimizations, and the conformations of the other lactones were studied with use of the molecular mechanics program MM3. The energies of the lactones estimated via molecular mechanics were compared with the experimental results.
- Wiberg, Kenneth B.,Waldron, Roy F.
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p. 7697 - 7705
(2007/10/02)
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- Intramolecular Cyclization of (ω-Carboxyalkyl)sulfonium Salts. A Novel Synthesis of Macrocyclic Lactones
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A useful method for the synthesis of macrocyclic lactones using (ω-carboxyalkyl)sulfonium salts was developed.Base-catalyzed intramolecular cyclization of (ω-carboxyalkyl)diphenylsulfonium salts 2 gave simple macrocyclic lactones in high yields at high dilution conditions. (ω-Carboxyalkyl)alkylphenylsulfonium salts 8 afforded simple macrocyclic lactone 6a and alkyl carboxylates 9.The reactions of (ω-carboxyalkyl)dialkylsulfonium salts 10 gave only esters without lactonization product 6a.The cyclization of S-(ω-carboxyalkyl)thiolanium salts 3 and S-(ω-carboxyalkyl)-2-methylthiolanium salts 4 took place readily under similar conditions to afford sulfur-containing macrocyclic lactones 13 and 15, respectively, in good yields.To investigate the reaction mechanism, sulfonium salt 25, having an optically active carbon atom, was prepared.The intramolecular cyclization of 25 took place with an inversion of configuration at chiral carbon atom to give ricinelaidic acid lactone (26; optical purity 66percent).
- Matsuyama, Haruo,Nakamura, Takako,Kamigata, Nobumasa
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p. 5218 - 5223
(2007/10/02)
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- N-NITROSATION AND N-NITRATION OF LACTAMS. FROM MACROLACTAMS TO MACROLACTONES
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N-Nitroso and N-nitro derivatives of lactams, from 2-pyrrolidinone to 15-pentadecanelactam, have been characterized by 1H NMR, 13C NMR, and IR spectroscopy.The conversion of these nitrosolactams and nitrolactams to lactones has been systematically (re)investigated.
- Torra, Nuria,Urpi, Felix,Vilarrasa, Jaume
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p. 863 - 868
(2007/10/02)
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- Novel Synthesis of Macrocyclic Lactones from ω-Carboxyalkylsulfonium Salts
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An intramolecular cyclization of S-(ω-carboxyalkyl)thiolanium salts took place readily under weakly basic conditions to afford sulfur-containing macrocyclic lactones in good yields.
- Matsuyama, Haruo,Nakamura, Takako,Takatsuka, Akinori,Kobayashi, Michio,Kamigata, Nobumasa
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p. 1931 - 1932
(2007/10/02)
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- From Azido Acids to Macrolactams and Macrolactones
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A new method is reported for the conversion of azido acids into lactams, via thioester formation and in situ azide reduction and cyclisation under high-dilution conditions; since the quantitative conversion of macrolactams to macrolactones has been shown to be feasible, this results in an indirect, alternative macrolactonisation procedure.
- Bartra, Marti,Bou, Valenti,Garcia, Jordi,Urpi, Felix,Vilarrasa, Jaume
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p. 270 - 272
(2007/10/02)
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- A Simple and Mild Esterification Method for Carboxylic Acids Using Mixed Carboxylic-Carbonic Anhydrides
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A simple and mild esterification method using mixed carboxylic-carbonic anhydrides has been developed.Simple aliphatic carboxylic esters are prepared in high yields by the reaction of acids with equimolar amounts of chloroformates (2,2,2-trichloroethyl chloroformate is an exception) and triethylamine in the presence of a catalytic amount of 4-(dimethylamino)pyridine.Although aromatic acids give a mixture of the ester, the acid anhydride, and the carbonate under normal conditions utilized in this study, it is found that increasing the amount of 4-(dimethylamino)pyridine drastically decreases the formation of the acid anhydride and the carbonate, affording a satisfactory yield of the ester.This method reaches a limit with sterically hindered acids and the formation of the acid anhydride and the carbonate is favored.
- Kim, Sunggak,Lee, Jae In,Kim, Youn Chul
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p. 560 - 565
(2007/10/02)
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- A New and Effective Synthetic Method for the Preparation of the Esters, Peptides, and Lactones Using 3-(5-Nitro-2-oxo-1,2-dihydro-1-pyridyl)-1,2-benzisothiazole 1,1-Dioxide. Synthesis of (+/-)-E-Dodecen-11-olide, Recifeiolide
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3-(5-nitro-2-oxo-1,2-dihydro-1-pyridyl)-1,2-benzisothiazole 1,1-dioxide (BID-NPy), readily prepared from 3-chloro-1,2-benzisothiazole 1,1-dioxide and 5-nitro-2-pyridone, proved to be a very useful condensing reagent.A variety of esters, dipeptides, and lactones were obtained in excellent yields.Furthemore, BID-NPy was successfully employed for the lactonization step in a new synthesis of a naturally occuring (+/-)-(E)-8-dodecen-11-olide, recifeiolide.
- Ahmed, Alauddin,Taniguchi, Nagahiro,Fukuda, Hirohiko,Kinoshita, Hideki,Inomata, Katsuhiko,Kotake, Hiroshi
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p. 781 - 786
(2007/10/02)
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- BAEYER-VILLIGER OXIDATION WITH Me3SiOOSiMe3 UNDER ASSISTANCE OF SnCl4 OR BF3-OEt2.
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Treatment of ketones with bis(trimethylsilyl) peroxide and Lewis acid such as SnCl//4 or BF//3-OEt//2 in dichloromethane at room temperature affords esters in fair to excellent yields. Jasmine lactone is synthesized from 2- left bracket (Z)-pentenyl right bracket cyclopentanine by means of Me//3SiOOSiMe//3-BF//3-OEt//2 system without any protection of the carbon-carbon double bond. The oxidation of enol acetates of ketones to alpha -hydroxy (or alpha -acetoxy) ketones with Me//3SiOOSiMe//3-FeCl//3 system is also disclosed.
- Matsubara,Takai,Nozaki
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p. 2029 - 2032
(2007/10/02)
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- Tin-mediated esterification in macrolide synthesis
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A neutral and relatively simple new method for effecting internal macrocyclic esterification of omega -hydroxycarboxylic acids, based on a tin 'template-driven' extrusion process, is discussed and its application to the synthesis (macrocyclization step) of the macrolide antibiotics zearalenone, ingramycin, and nodusmicin detailed. An efficient, formal total synthesis of pyrenophorin using this technique is also presented. Attempts to extend the methodology to include the macrocyclization of omega -bromo carboxylic acids or omega -mercapto carboxylic acids were unsuccessful. However, although beta - and omega -amino carboxylic acids preferentially gave way to polymer formation, 4-,5, and 6-amino carboxylic acids readily condensed to give the corresponding five-, six-, and seven-membered lactams in excellent yields. For example, in this way, the bridged lactam 1-azabicyclo- left bracket 3. 3. 1 right bracket nonan-2-one was prepared in 77% yield as compared to the previously reported yield of less than 2%.
- Steliou,Poupart
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p. 7130 - 7138
(2007/10/02)
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- Template-Driven Macrolide Closures.
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Thiol-functionalized crown ethers serve as reagents for macrolide closures.The thioesters derived from these crown ethers and ω-hydroxy carboxylic acids yield macrolides when treated with potassium tert-butoxide.The cyclization reaction proceeds via a templated conformation in which the ω-alkoxide is held proximate to the thioester through ionic bonding to the crown-bound potassium cation.Variations in crown ether structure in the series 1-4 show that the criterion of proximate binding is necessary but not sufficient to ensure efficient macrolide closure.The optimal crown ether reagent is thought to provide transition-state stabilization for the attack of the alkoxide on the thioester carbonyl by situating the carbonyl oxygen immediately adjacent to the crown-bound potassium cation.
- Rastetter, William H.,Phillion, Dennis P.
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p. 3209 - 3214
(2007/10/02)
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- Preparation of Macrocyclic Lactones by Ring Closure of Cesium Carboxylates
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A series of ω-halo fatty acids, the longest being 16-iodohexadecanoic acid, was prepared by oxidation of the corresponding ketones with m-chloroperbenzoic acid in boiling chloroform, followed by ring opening usually with hydrogen iodide in acetic acid at 100 deg C.Solutions of these acids in dimethylformamide (DMF) at concentrations of 5E-3 - 5E-2 M were treated with an equivalent amount of dry Cs2CO3.The solutions were stirred at 40 deg C overnight.Workup of the reaction mixture produced a mixture of (macro)cyclic lactone (macrolide) and its dimer (dilide).For the case of 16-iodohexanoic acid the lactone was isolated in 85percent yield.Yields for other large ring macrolides were also excellent.It was demonstrated that substitution by carboxylate on a secondary halide also goes well to afford the corresponding macrolide with no detectable amount of elimination.The effects of ring size, concentration, and solvent on the ring closure of the cesium carboxylates formed in situ were investigated.DMF is the best solvent of those investigated for the ring closure.Cesium carboxylates also undergo more readily ring closure and in far better yield than the carboxylates of lithium, sodium, potassium, rubidium, silver, thallium, magnesium, strontium, or barium.The S-lactone of ricinelaidic acid was prepared optically pure in 80percent yield from optically pure mesylate of R-ricinelaidic acid, which was treated with cesium carbonate in dry DMF.This demonstrates that the ring closure proceeds with the anticipated SN2 inversion at the hydroxyl-bearing carbon atom.With the same approach optically pure S-zearalenone was protected and subjected to ring opening, and the hydroxyl group was activated as mesylate.Some racemization was found to occur in the ring-opening step.On treatment of this material with dry cesium carbonate in DMF, the desired ring closure took place in 80percent yield to provide an excess of the protected R enantiomer of zearalenone.On the basis of these results, some speculations are made concerning the action of cesium in promoting ring closure to macrocyclic lactones.
- Kruizinga, Wim H.,Kellogg, Richard M.
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p. 5183 - 5189
(2007/10/02)
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- Transition-State-Stabilized Macrolide Closures
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Thiol-functionalized crown ethers serve as reagents for macrolide closures.The thioesters derived from these crown ethers and ω-hydroxy carboxylic acids yield macrolides when treated with potassium tert-butoxide.The reaction proceeds via a templated conformation in which the ω-alkoxide is held proximate to the thioester through ionic bonding to the crown-bound potassium cation.Variations in crown ether structure show that the criterion of proximate binding is necessary but not sufficient to ensure efficient macrolide closure.The optimal crown ether reagent provides transition-state stabilization for the attack of the alkoxide on the thioester carbonyl by situating the carbonyl oxygen immediately adjacent to the crown-bound potassium cation.
- Rastetter, William H.,Phillion, Dennis P.
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p. 1535 - 1538
(2007/10/02)
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