- Syntheses of Gymnothespirolignans B and C and Non-natural Isomer 9-Epi-gymnothespirolignan B
-
Syntheses of polycyclic spiro lignans gymnothespirolignans B and C as well as the unnatural isomer 9-epi-gymnothespirolignan B were accomplished using (R)-Roche ester and an appropriately substituted fluorenone. Key features of the convergent syntheses include coupling of the fluorenone and an iodo-alkene intermediate derived from (R)-Roche ester in the presence of the Lewis acid TiCl(OiPr)3, C9-O bond formation via an SN2 reaction with retention of stereochemistry, and diastereoselective hydrogenations of a common alkene intermediate guided by accessibility or positioning by the C8-methoxy.
- Ali, Ghada,Cuny, Gregory D.
-
supporting information
p. 10517 - 10525
(2021/07/31)
-
- Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**
-
Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.
- Cunha, Ana V.,Havenith, Remco W. A.,Holzheimer, Mira,Minnaard, Adriaan J.,Schouten, Stefan,Sinninghe Damsté, Jaap S.
-
supporting information
p. 17504 - 17513
(2021/07/06)
-
- The discovery and evaluation of 3-amino-2(1H)-pyrazinones as a novel series of selective p38α MAP kinase inhibitors
-
The discovery and optimisation of a novel series of potent and selective p38α inhibitors is described. Evaluating the structure-activity relationship of an aminoalkyl substituent at the 3 position of the 2(1H)-pyrazinone core, p38α potency was increased 20000-fold. The most advanced compound (25) demonstrated excellent in vivo properties suitable for an inhaled route of administration.
- Evans, Richard,Raubo, Piotr,Willis, Paul
-
supporting information
(2020/07/21)
-
- Ring-closing metathesis approaches towards the total synthesis of rhizoxins
-
Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ringclosure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) E double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.
- Altmann, Karl-Heinz,Liniger, Marc,Neuhaus, Christian M.
-
supporting information
(2020/10/18)
-
- Stereoselective Synthesis of the C1-C22 Carbon Framework of (-)-Amphidinolide K
-
Two stereoselective routes to the C7-C22 subunit of amphidinolide K are disclosed. Jacobsen's hydrolytic kinetic resolution and Sharpless' asymmetric dihydroxylation reactions have been employed for the construction of the tetrahydrofuran ring. The C10-C1
- Chandankar, Somnath S.,Raghavan, Sadagopan
-
p. 9584 - 9602
(2019/09/06)
-
- A natural ɑ - glucosidase inhibitor Penasulfate A synthetic method (by machine translation)
-
The invention provides a natural ɑ - glucosidase inhibitor Penasulfate A synthetic method, including by the 1, 12 - dodecanediol via 5 step synthesis 12 - thirteen carbon olefine acid, L - arabinose via the 3 step synthesis (2 S, 3 R) - 2, 3 - oxygen - isopropyl - 4 - pentene - 1, 2, 3 - triol, (S)- Roche ester via the 8 step synthesis of chiral methyl undecenyl fundamental frequency that mellow boron ester, 12 - thirteen alkenylene acid and (2 S, 3 R) - 2, 3 - oxygen - isopropyl - 4 - pentene - 1, 2, 3 - triol in GrubbsII catalyst under the action of the olefin metathesis reaction, and then with the (R)- piperidine - 2 - carboxylic acid methyl ester reaction to prepare amide, re-oxidation results in the aldehyde, Takai alkene alkylation by thirteen alkenylene iodide, with the insecticidal compositions of the fundamental frequency that chiral methyl mellow boron ester in Pd (PPh3 )4 Catalytic, ethyl alcohol thallium as alkali under the condition of the key Suzuki coupling, hydrogenation reduction, [...], sulfuric acid ester, shall Penasulfate A. The present invention provides natural product Penasulfate A throughout the synthetic route for the first time, the olefin metathesis reactions and Suzuki coupling as a key reaction, the line is comparatively simple high efficiency, a high degree of convergence, the operation is easy to grasp. (by machine translation)
- -
-
Paragraph 0029; 0050; 0051
(2019/02/04)
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- Total Synthesis of the Proposed Structure of Penasulfate A: L -Arabinose as a Source of Chirality
-
The total synthesis of putative penasulfate A was effectively achieved by a convergent strategy with a longest linear sequence of 14 steps and overall yield of 8.6%. The highlights of our strategy involved an E-selective olefin cross-metathesis, Suzuki cross-coupling, and a copper(I)-catalyzed coupling reaction.
- Gao, Yangguang,Cao, Zhou,Zhang, Qiang,Guo, Rui,Ding, Fei,You, Qingliang,Bi, Jingjing,Zhang, Yongmin
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p. 1908 - 1916
(2019/08/20)
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- Polyoxygenated Tertiary Alcohols: A Kiyooka Approach
-
A Kiyooka aldol approach for the stereoselective synthesis of tertiary alcohols is presented. This approach allows for the incorporation of different substituents at all three remaining positions at the chiral center bearing the tertiary alcohol. To demon
- Lücke, Daniel,Kalesse, Markus
-
supporting information
p. 10080 - 10083
(2019/07/18)
-
- (R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes
-
The synthesis of potent metabolically stable endocannabinoids is challenging. Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13S,1′R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1 receptor (Ki o
- Liu, Yingpeng,Ji, Lipin,Eno, Marsha,Kudalkar, Shalley,Li, Ai-Ling,Schimpgen, Marion,Benchama, Othman,Morales, Paula,Xu, Shu,Hurst, Dow,Wu, Simiao,Mohammad, Khadijah A.,Wood, Jodianne T.,Zvonok, Nikolai,Papahatjis, Demetris P.,Zhou, Han,Honrao, Chandrashekhar,MacKie, Ken,Reggio, Patricia,Hohmann, Andrea G.,Marnett, Lawrence J.,Makriyannis, Alexandros,Nikas, Spyros P.
-
supporting information
p. 8639 - 8657
(2018/10/02)
-
- Stereocontrolled Synthesis of Polypropionate Fragments based on a Building Block Assembly Strategy using Lithiation-Borylation Methodologies
-
Polypropionates are important structural motifs in nature and are commonly made by iterative aldol or crotylation methodologies. Herein, an alternative strategy is presented in which stereochemically predefined building blocks, bearing appropriate functio
- Millán, Alba,Grigol Martinez, Pablo D.,Aggarwal, Varinder K.
-
supporting information
p. 730 - 735
(2018/01/26)
-
- Stereoselective synthesis of the C3-C15 fragment of callyspongiolide
-
The synthesis of C3-C15 fragment of callyspongiolide, a 14-membered macrolides isolated from the marine sponge Callyspongia sp., which was collected from the Indonesia, is reported. Highlights of the synthesis include construction of E-olefin through Juli
- Reddy Ramidi, Gopal,Yadav, Jhillu S.,Mohapatra, Debendra K.
-
supporting information
p. 3579 - 3582
(2018/09/10)
-
- Stereoselective total synthesis of 10-epi-tirandamycin E
-
A stereoselective total synthesis of 10-epi-tirandamycin E is described, employing desymmetrization protocol, ring-closing metathesis (RCM), acid-catalyzed ketalization, substrate controlled dihydroxylation and Horner-Wadsworth-Emmons olefination as key r
- Yadav, Jhillu S.,Dhara, Santu,Mohapatra, Debendra K.
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p. 1358 - 1366
(2017/02/13)
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- Quinocidin, acytotoxic antibiotic with anunusual 3,4-dihydroquinolizinium ring and michael acceptor reactivity toward thiols
-
Cytotoxicity-guided fractionation of the culture broth of Actinomadura sp. TP-A0019 led to the isolation of quinocidin (1), acytotoxic antibiotic with an unusual 3,4-dihydroquinolizinium ring. The structural assignment was made on the basis of high-field NMR experiments and chemical synthesis. Comparison ofthe spectral properties of 1 with those of its synthetic counterparts revealed that 1 is aracemic mixture of two enantiomers, which showed similar cytotoxicity against HeLa-S3 cells. Nucleophile-trap-ping experiments demonstrated that 1 captured 2-mer-captoethanol and N-acetyl-l-cysteine by means of aMi-chael addition-type reaction, but was inert toward 2-ami-noethanol and glycolic acid. Notably, the addition of 1 to thiols proceeded smoothly in neutral aqueous media at room temperature. In view of the thiol-trapping ability and the unusual structure, 1 provides aunique scaffold for designing drug leads and protein-labeling probes.
- Nakagawa, Yu,Sawaki, Yuki,Kimura, Takahiro,Tomura, Tomohiko,Igarashi, Yasuhiro,Ojika, Makoto
-
supporting information
p. 17894 - 17897
(2019/03/07)
-
- Stereospecific Allylic Functionalization: The Reactions of Allylboronate Complexes with Electrophiles
-
Allylboronic esters react readily with carbonyls and imines (π-electrophiles), but are unreactive toward a range of other electrophiles. By addition of an aryllithium, the corresponding allylboronate complexes display enhanced nucleophilicity, enabling addition to a range of electrophiles (tropylium, benzodithiolylium, activated pyridines, Eschenmoser's salt, Togni's reagent, Selectfluor, diisopropyl azodicarboxylate (DIAD), MeSX) in high regio- and stereocontrol. This protocol provides access to key new functionalities, including quaternary stereogenic centers bearing moieties such as fluorine and the trifluoromethyl group. The allylboronate complexes were determined to be 7 to 10 orders of magnitude more reactive than the parent boronic ester.
- García-Ruiz, Cristina,Chen, Jack L.-Y.,Sandford, Christopher,Feeney, Kathryn,Lorenzo, Paula,Berionni, Guillaume,Mayr, Herbert,Aggarwal, Varinder K.
-
supporting information
p. 15324 - 15327
(2017/11/06)
-
- Geometry-selective synthesis of the unsaturated side chains of the isodomoic acids
-
Abstract Three unsaturated vinylic or allylic halides were made in enantiomerically pure form, ready for coupling with a vinyl metal as part of a divergent strategy for the synthesis of members of the domoic/isodomoic acid family and their analogues. The
- Fleary-Roberts, Nadia,Lemière, Gilles,Clayden, Jonathan
-
p. 7204 - 7208
(2015/03/18)
-
- The amido-pentadienoate-functionality of the rakicidins is a thiol reactive electrophile - Development of a general synthetic strategy
-
We demonstrate that a unique class-defining functionality (mc-APD) found in macrocyclic natural products with potent anti-cancer activity, imparts these compounds with electrophilic reactivity. The mc-APD group represents an interesting structural hybrid between canonical biologically relevant Michael-acceptors. Further, a novel thiol-elimination method for preparation of the mc-APD group is outlined.
- Clement, Lise L.,Tsakos, Michail,Schaffert, Eva S.,Scavenius, Carsten,Enghild, Jan J.,Poulsen, Thomas B.
-
supporting information
p. 12427 - 12430
(2015/08/03)
-
- Short stereoselective synthesis of the phytophthora universal mating hormone α1 using lithiation/borylation reactions
-
The universal mating hormone α 1 of the virulent plant pathogen Phytophthora has been synthesized in 12 steps and 28 % overall yield. Key CC bond-forming steps involved the use of two lithiation/borylation reactions to couple together enantioenriched building blocks, one of which also set up the stereochemistry of the tertiary alcohol at C11. Detailed analysis showed that the diastereomeric purity of the target molecule was >91 %, the highest obtained to date. In search of a mate: The universal mating hormone α 1 of the virulent plant pathogen Phytophthora has been synthesized in 12?steps and 28 % overall yield. Key CC bond-forming steps involved the use of two lithiation/borylation reactions to couple together enantioenriched building blocks, one of which also set up the stereochemistry of the tertiary alcohol at C11. The diastereomeric purity of the target molecule is >91 %, the highest obtained to date.
- Pulis, Alexander P.,Fackler, Philipp,Aggarwal, Varinder K.
-
supporting information
p. 4382 - 4385
(2014/05/06)
-
- Convergent approach to complex spirocyclic pyrans: Practical synthesis of the oxa-pinnaic acid core
-
The enantioselective synthesis of the oxa-pinnaic acid framework has been achieved through internal asymmetric induction. The synthetic strategy pursued illustrates the adaptability of the Achmatowicz oxidative rearrangement for the synthesis of complex spirocyclic pyrans starting from tertiary alcohols. The Royal Society of Chemistry.
- Ferrari, Frank D.,Pasqua, Adele E.,Ledgard, Andrew J.,Marquez, Rodolfo
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p. 3469 - 3476
(2013/06/05)
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- Synthesis of key fragments of 19-membered cytotoxic macrolide amphidinolide e
-
Amphidinolide E is a 19-membered macrolide possessing potent cytoxic activity. The macrolide core having two key intermediates alcohol and acid was synthesized efficiently. The THF ring segment was synthesized from Dglucose as chiral precursor, whereas th
- Mohapatra, Seetaram,Nayak, Sabita,Mishra, Sambita K.,Pattanaik, Priyabrata
-
supporting information
p. 65 - 69
(2013/07/26)
-
- Synthesis of (-)-hennoxazole A: Integrating batch and flow chemistry methods
-
A new total synthesis of (-)-hennoxazole A is reported. The synthetic approach is based on the preparation of three similarly sized fragments resulting in a fast and convergent assembly of the natural product. The three key reactions of the synthesis include a highly stereoselective 1,5-anti aldol coupling, a gold-catalyzed alkoxycyclization reaction, and a stereocontrolled diene cross-metathesis. The synthesis involves integrated batch and flow chemistry methods leading to the natural product in 16 steps longest linear sequence and 2.8% overall yield. Georg Thieme Verlag Stuttgart · New York.
- Fernández, Amadeo,Levine, Zebulon G.,Baumann, Marcus,Sulzer-Mossé, Sarah,Sparr, Christof,Schl?ger, Sabrina,Metzger, Albrecht,Baxendale, Ian R.,Ley, Steven V.
-
supporting information
p. 514 - 518
(2013/04/10)
-
- Highly stereocontrolled total synthesis of β-d-mannosyl phosphomycoketide: A natural product from mycobacterium tuberculosis
-
β-d-Mannosyl phosphomycoketide (C32-MPM), a naturally occurring glycolipid found in the cell walls of Mycobacterium tuberculosis, acts as a potent antigen to activate T-cells upon presentation by CD1c protein. The lipid portion of C32-MPM contains a C32-mycoketide, consisting of a saturated oligoisoprenoid chain with five chiral methyl branches. Here we develop several stereocontrolled approaches to assemble the oligoisoprenoid chain with high stereopurity (>96%) using Julia-Kocienski olefinations followed by diimide reduction. By careful choice of olefination sites, we could derive all chirality from a single commercial compound, methyl (2S)-3-hydroxy-2-methylpropionate (>99% ee). Our approach is the first highly stereocontrolled method to prepare C32-MPM molecule with >96% stereopurity from a single >99% ee starting material. We anticipate that our methods will facilitate the highly stereocontrolled synthesis of a variety of other natural products containing chiral oligoisoprenoid-like chains, including vitamins, phytol, insect pheromones, and archaeal lipids.
- Li, Nan-Sheng,Scharf, Louise,Adams, Erin J.,Piccirilli, Joseph A.
-
p. 5970 - 5986
(2013/07/26)
-
- Synthesis of stereopure acyclic 1,5-dimethylalkane chirons: Building blocks of highly methyl-branched natural products
-
An efficient synthetic method towards stereopure acyclic 1,5-dimethylalkane building blocks from methyl (2R)-3-hydroxy-2-methylpropionate (R)-1 (>99% ee) and methyl (2S)-3-hydroxy-2-methylpropionate (S)-1 (>99% ee) through a series of chemical transformat
- Li, Nan-Sheng,Piccirilli, Joseph A.
-
p. 9633 - 9641
(2013/10/22)
-
- PROCESS FOR PREPARATION OF (3R)-2,4-DI-LEAVING GROUP-3-METHYLBUT-1-ENE
-
The specification relates to compounds and process for the preparation of a compound of formula 7, where LG is a leaving group and hal is a halide and is Cl, Br or I. The compound of formula 7 can be useful in the preparation of natural products, such as
- -
-
Paragraph 0061-0062
(2013/06/27)
-
- Stereoselective synthesis of the C5-C18 fragment of halichomycin
-
An efficient and convergent synthesis of the C5-C18 fragment of halichomycin is reported. Butanolide fragment 6 was readily prepared stereoselectively from (R)-Roche ester through catalyst control; dienylic bromide domain 7 was synthesized from (S)-serine by substrate control. C 5-C18 fragment 2 was rapidly assembled through a stereoselective alkylation of the butanolide with the dienylic bromide, followed by functional group transformations.
- Li, Qingjiang,Mao, Shiyong,Cui, Yuxin,Jia, Yanxing
-
scheme or table
p. 4111 - 4116
(2012/06/18)
-
- Step-economic synthesis of (+)-crocacin C: A concise crotylboronation/[3,3] -sigmatropic rearrangement approach
-
The step-economic total synthesis of (+)-crocacin C has been achieved in 20% yield from commercially available starting materials. This approach requires the isolation of only 8 intermediates and can provide a reliable supply of (+)-crocacin C for the development of new antifungal and crop protection agents.
- Pasqua, Adele E.,Ferrari, Frank D.,Hamman, Chris,Liu, Yanzhou,Crawford, James J.,Marquez, Rodolfo
-
experimental part
p. 6989 - 6997
(2012/09/25)
-
- Enantioselective synthesis of (10S)- and (10R)-methyl-anandamides
-
For the development of novel endocannabinoid templates with potential resistance to hydrolytic and oxidative metabolism, we are targeting the bis-allylic carbons of the arachidonoyl skeleton. Toward this end, we recently disclosed the synthesis and prelim
- Nikas, Spyros P.,D'Souza, Marsha,Makriyannis, Alexandros
-
supporting information; experimental part
p. 6329 - 6337
(2012/09/08)
-
- Tumescenamide C, an antimicrobial cyclic lipodepsipeptide from Streptomyces sp.
-
Tumescenamide C, a new cyclic lipodepsipeptide, was isolated from a culture broth of an actinomycete Streptomyces sp. KUSC-F05. Tumescenamide C was a congener of tumescenamides A and B, representing a sixteen-membered ring system, consisting of two proteinogenic and three non-proteinogenic amino acids, to which a methyl-branched fatty acid was attached. The planar structure was determined by spectroscopic analysis, while its absolute stereochemistry was determined by chemical degradation and asymmetric synthesis. Tumescenamide C exhibited antimicrobial activity with high selectivity against Streptomyces species.
- Kishimoto, Shinji,Tsunematsu, Yuta,Nishimura, Shinichi,Hayashi, Yutaka,Hattori, Akira,Kakeya, Hideaki
-
experimental part
p. 5572 - 5578
(2012/09/08)
-
- Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics
-
The HCV non-structural protein NS5A has been established as a viable target for the development of direct acting antiviral therapy. From computational modeling studies strong intra-molecular hydrogen bonds were found to be a common structural moiety withi
- Chang, Wonsuk,Mosley, Ralph T.,Bansal, Shalini,Keilman, Meg,Lam, Angela M.,Furman, Phillip A.,Otto, Michael J.,Sofia, Michael J.
-
scheme or table
p. 2938 - 2942
(2012/06/15)
-
- Formal synthesis of (+)-crocacin C
-
The formal synthesis of (+)-crocacin C is reported. The approach described takes advantage of a highly regioselective epoxide cuprate addition and a diastereoselective Overman rearrangement. The synthesis is practical and amenable to scale up.
- Pasqua, Adele E.,Ferrari, Frank D.,Crawford, James J.,Marquez, Rodolfo
-
scheme or table
p. 2114 - 2116
(2012/07/13)
-
- Total synthesis of carolacton, a highly potent biofilm inhibitor
-
Metals are the key players in the synthesis of caralacton, a strong inhibitor of bacterial biofilms. The total synthesis is based on several metal-mediated key transformations such as the Ley and the Duthaler-Hafner aldol reactions, the Marshall reaction and Breit's substitution, as well as the Nozaki-Hiyama-Kishi and Negishi-Fu C-C coupling reactions. Copyright
- Schmidt, Thomas,Kirschning, Andreas
-
supporting information; experimental part
p. 1063 - 1066
(2012/03/11)
-
- Studies for the enantiocontrolled preparation of substituted tetrahydropyrans: Applications for the synthesis of leucascandrolide A macrolactone
-
Strategies for the stereocontrolled preparations of 2,6-cis- and 2,6-trans-substituted tetrahydropyrans have been devised. These studies have explored methodology for asymmetric induction in SE′ reactions using chiral 1,3,2-diazaborolidine controllers. Reactions with aldehydes at -78°C yield nonracemic 1,5-diols for chemoselective internal backside displacements. This concept is developed as a flexible and reliable strategy in studies toward leucascandrolide A macrolactone 2 via the sequential applications of SE′ reactions leading to the C1-C9 aldehyde 14, and the bis-tetrahydropyran 59, respectively.
- Williams, David R.,Plummer, Scott V.,Patnaik, Samarjit
-
scheme or table
p. 5083 - 5097
(2011/07/31)
-
- Remarkable synergistic effect between MonBI and MonBII on epoxide opening reaction in ionophore polyether monensin biosynthesis
-
Enzymatic epoxide-opening cascade is one of the key biosynthetic processes for constructing structurally diverse polyethers. Here we report the first in vitro analysis of the cyclization catalyzed by two epoxide hydrolases, MonBI and MonBII involved in mo
- Sato, Kyohei,Minami, Atsushi,Ose, Toyoyuki,Oguri, Hiroki,Oikawa, Hideaki
-
scheme or table
p. 5277 - 5280
(2011/10/30)
-
- Studies culminating in the total synthesis and determination of the absolute configuration of (-)-saudin
-
A full account of studies that culminated in the total synthesis of both antipodes and the assignment of its absolute configuration of Saudin, a hypoglycemic natural product. Two approaches are described, the first proceeding though bicyclic lactone intermediates and related second monocyclic esters. The former was obtained via asymmetric Diels-Alder cycloaddition and the latter by an asymmetric annulation protocol. Both approaches employ a Lewis acid promoted Claisen rearrangement, with the successful approach taking advantage of bidentate chelation to control the facial selectivity of the key Claisen rearrangement.
- Boeckman Jr., Robert K.,Rosario Ferreira, Maria Rico Del,Mitchell, Lorna H.,Shao, Pengcheng,Neeb, Michael J.,Fang, Yue
-
experimental part
p. 9787 - 9808
(2012/02/05)
-
- A general synthetic approach to the amnesic shellfish toxins: Total synthesis of (-)-isodomoic acid B, (-)-isodomoic acid E and (-)-isodomoic acid F
-
The alkynylpyrrolidine 4 was made via a dearomatising cyclisation of an aromatic amide, and was elaborated by stannylcupration and palladium-catalysed coupling to achieve the first total synthesis of three members of the isodomoic acid family; the same alkyne can be envisaged as a precursor to several more of this class of amnesic shellfish toxins. The Royal Society of Chemistry.
- Lemiere, Gilles,Sedehizadeh, Simon,Toueg, Julie,Fleary-Roberts, Nadia,Clayden, Jonathan
-
supporting information; experimental part
p. 3745 - 3747
(2011/05/04)
-
- Total synthesis of iso- and bongkrekic acids: Natural antibiotics displaying potent antiapoptotic properties
-
For over five decades, owing to their antiapoptotic activities, bongkrekic and isobongkrekic acids have generated interest from the scientific community. Here, we disclose full details of our investigation into the synthesis of isobongkrekic acid, which culminated in its first preparation and features various palladium-catalysed cross-couplings and Takai olefination reactions. Access to bongkrekic acid is also reported by this route. These syntheses involve the preparation and use of new general building blocks which could find wider applications. Iso-bong: A versatile first synthesis of isobongkrekic acid (IBA) has been developed. Key steps include three different palladium cross-couplings and an asymmetric homopropargylation. In-depth synthetic studies reveal the challenges faced in generating the right geometry of each diene.
- Francais, Antoine,Leyva-Perez, Antonio,Etxebarria-Jardi, Gorka,Pena, Javier,Ley, Steven V.
-
supporting information; experimental part
p. 329 - 343
(2011/03/21)
-
- Synthetic efforts toward the spiroketal core of spirangien a
-
(Figure presented) Synthetic studies toward the spiroketal core of spirangien A are described. Two synthetic approaches were developed. Both of them use a diastereoselective aldol addition of a lithium enolate derived from a methyl ketone on an aldehyde. In the first approach, the introduction of the (E)-trisubstituted terminal olefin was achieved by using an iron-catalyzed cross-coupling between an alkyl iodide and a vinyl Grignard reagent and a randomly protected spiroketal was obtained. In the second approach, a highly functionalized spiroketal carbamate, which includes 13 stereogenic centers, was successfully isolated.
- Guerinot, Amandine,Lepesqueux, Guillaume,Sable, Serge,Reymond, Sebastien,Cossy, Janine
-
scheme or table
p. 5151 - 5163
(2010/10/03)
-
- Design and synthesis of (135)-methyl-substituted arachidonic acid analogues: Templates for novel endocannabinoids
-
Two novel methyl-substituted arachidonic acid derivatives were prepared in an enantioselective manner from commercially available chiral building blocks, and were found to be excellent templates for the development of (13S)methyl-substituted anandamide an
- Papahatjis, Demetris P.,Nahmias, Victoria R.,Nikas, Spyros P.,Schimpgen, Marion,Makriyannis, Alexandras
-
supporting information; experimental part
p. 4091 - 4099
(2010/08/05)
-
- An asymmetric hydrogenation route to (-)-Spongidepsin
-
Figure Presented. (-)-Spongidepsin 1, a cytotoxic marine natural product, was prepared via two iridium-catalyzed hydrogenation reactions; both were highly stereoselective, giving convenient access to pivotal intermediates. This synthesis was modified to g
- Zhu, Ye,Loudet, Aurore,Burgess, Kevin
-
scheme or table
p. 4392 - 4395
(2010/12/18)
-
- Total synthesis and biological evaluation of tyroscherin
-
Figure Presented. The efficient synthesis and biological evaluation of both the reported and revised structures of tyroscherin have been achieved. Central to our synthesis is a cross metathesis reaction that generated the trans-olefin regioselectively. Th
- Tae, Hyun Seop,Hines, John,Schneekloth, Ashley R.,Crews, Craig M.
-
supporting information; experimental part
p. 4308 - 4311
(2010/12/20)
-
- Synthesis of the sponge-derived plakortone series of bioactive compounds
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The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex have provided a series of biologically active furanolactones the plakortones A-D (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of the plakortones is a sterically congested 2,6-dioxabicyclo[3. 3.0]octan-3-one moiety, the emblematic furanolactone core. This core is efficiently accessed by a palladium(II) mediated hydroxycyclization- carbonylation-lactonization cascade with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6) are now described which settle constitutional and stereochemical features in this group of secondary metabolites. Acquisition of plakortone D (4), the most effective activator of SR-Ca2+-pumping ATPase, utilized stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 29. A derived lactone aldehyde was then coupled with an independently generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond, carried through the sequence as a protected, stereodefined diol, was released therefrom by stereospecific syn-elimination via an orthoester derivative. In this way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E) configuration. Racemic plakortone E (5) was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 52 was assembled first. Plakortone C (3) resulted from a sequence commencing with (R)-(+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated primary alcohol 79 was converted by standard procedures to key enediol 89 which, with the Pd(II) protocol, afforded the major separable plakortones 90 and 91, with the former being identical with natural plakortone C (3). Very mild hydrogenation of 90 afforded a saturated plakortone, identical with natural plakortone F (6), thus establishing its structure and absolute stereochemistry. Available information on the stereoselective routes to plakortones E (5) and B (2) are also outlined, so that the constitution and absolute stereochemistry of plakortones B-F are now established.
- Hayes, Patricia Y.,Chow, Sharon,Rahm, Fredrik,Bernhardt, Paul V.,De Voss, James J.,Kitching, William
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scheme or table
p. 6489 - 6501
(2010/12/24)
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- Evolution of the total synthesis of (-)-Okilactomycin exploiting a tandem oxy-cope rearrangement/oxidation, a petasis-ferrier union/rearrangement, and ring-closing metathesis
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An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration,has been achieved exploiting a convergent strategy. Highlights of the s ynthesis include a diastereoselective o
- Smith, Amos B. III,Bosanac, Todd,Basu, Kallol
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scheme or table
p. 2348 - 2358
(2009/07/30)
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- A formal total synthesis of dictyostatin
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A convergent formal synthesis of the antimitotic macrolide dictyostatin has been achieved. The C11-C26 fragment of dictyostatin was prepared via convergent assembly of the central deoxypropionate motif utilizing a site- and stereoselective titanium-mediated reductive cross-coupling and an asymmetric hydrogenation of the resulting stereodefined 1,3-diene.
- Shimp, Heidi L.,Micalizio, Glenn C.
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scheme or table
p. 5908 - 5915
(2011/04/22)
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- The first enantioselective synthesis of palinurin
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The first enantioselective synthesis of palinurin has been accomplished starting from commercially available furaldehyde and (R)-methyl-3-hydroxy-2- methylpropionate; the key steps of the synthesis include the use of a chiral pyrrolidine to create the chiral tetronic moiety, and Horner-Wadsworth-Emmons, Wittig and Wittig-Horner reactions to construct the alkene units.
- Perez, Manuel,Perez, Daniel I.,Martinez, Ana,Castro, Ana,Gomez, Generosa,Fall, Yagamare
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supporting information; experimental part
p. 3252 - 3254
(2009/12/01)
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- Formal total synthesis of (-)-spongidepsin
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The formal total synthesis of (-)-spongidepsin is described. Three fragments I, II, and III were first prepared from readily available starting materials and then assembled to the target compound. The key steps involved in the synthesis are asymmetric α-hydroxylation, Ender's alkylation, and ring-closing metathesis reactions. An alternative route for the fragment II is also achieved involving Sharpless asymmetric epoxidation and Gilman's alkylation as key reactions.
- Chandrasekhar,Yaragorla,Sreelakshmi,Reddy, Ch. Raji
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p. 5174 - 5183
(2008/12/20)
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- Diastereodivergent Aldol reactions of β-alkoxy ethyl ketones: Modular access to (1,4)-syn and -anti polypropionates
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(Chemical Equation Presented) Asymmetric substrate-controlled aldol reactions of ethyl ketones of type 4 with aldehyde 3 are reported. Modular access to all possible syn-and anti-aldol products was obtained by careful choice of reaction conditions. To ach
- Arikan, Fatih,Li, Jun,Menche, Dirk
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supporting information; experimental part
p. 3521 - 3524
(2009/05/27)
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- Furan derivatives, method of synthesis and uses thereof
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The present invention relates to furan derivatives of formula (I), their method of synthesis and uses thereof. Concretely, the compounds disclosed have proved to be inhibitors of glycogen synthase kinase 3β, GSK-3 β, which is known to be involved in different disease and conditions, such as Alzheimer's disease or non-insulin dependent diabetes mellitus. The present invention also relates to pharmaceutical compositions comprising the same. Further, the present invention is directed to the use of the compounds in the manufacture of a medicament for the treatment and/or prevention of a GSK-3 mediated disease or condition.
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Page/Page column 29-30
(2008/12/06)
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- Modular synthesis of the C9-C27 degradation product of aflastatin a via alkyne-epoxide cross-couplings
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A modular approach to the synthesis of complex polyketide natural products is demonstrated for the synthesis of the C9-C27 degradation product from aflastatin A. The product of the cross-coupling of C23-C27 terminal alkyne with C17-C22 epoxide underwent f
- Robles, Omar,McDonald, Frank E.
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supporting information; experimental part
p. 1811 - 1814
(2009/04/10)
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- Stereoselective formal total synthesis of the cyclodepsipeptide (-)-spongidepsin
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The formal total synthesis of (-)-spongidepsin is achieved starting from easily available raw materials involving asymmetric α-hydroxylation, Enders alkylation, and RCM as key reactions.
- Chandrasekhar, Srivari,Yaragorla, Srinivasa Rao,Sreelakshmi, Lella
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p. 7339 - 7342
(2008/03/14)
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- A flexible synthetic approach to the hennoxazoles
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Three advanced intermediates corresponding to the carbon skeleton of the hennoxazoles have been prepared. Central to the strategy is the synthesis of the oxazoles prior to coupling with the other fragments and a dithiane addition to allow for the generati
- Zylstra, Eric J.,She, Miles W.-L.,Salamant, Walter A.,Leahy, James W.
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p. 623 - 627
(2007/10/03)
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