- The Formosalides: Structure Determination by Total Synthesis
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Total synthesis allowed the constitution of the cytotoxic marine macrolides of the formosalide family to be confirmed and their previously unknown stereostructure to be assigned with confidence. The underlying blueprint was inherently modular to ensure that each conceivable isomer could be reached. This flexibility derived from the use of strictly catalyst controlled transformations to set the stereocenters, except for the anomeric position, which is under thermodynamic control; as an extra safety measure, all stereogenic centers were set prior to ring closure to preclude any interference of the conformation adopted by the macrolactone rings of the different diastereomers. Late-stage macrocyclization by ring-closing alkyne metathesis was followed by a platinum-catalyzed transannular 6-exo-dig hydroalkoxylation/ketalization to craft the polycyclic frame. The side chain featuring a very labile unsaturation pattern was finally attached to the core by Stille coupling.
- Schulthoff, Saskia,Hamilton, James Y.,Heinrich, Marc,Kwon, Yonghoon,Wirtz, Conny,Fürstner, Alois
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- A Migratory Ether Formation Route to Medium-Sized Sugar Mimetics
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Polyol-substituted cyclic ethers are fundamental building blocks of biomolecules. The position and stereochemistry of multiple hydroxy substituents of cyclic ethers play a central role in their biological function. Current methods for the synthesis of such structures are limited to “naked” ring products with no or few substituents. Here we describe a general route to medium-sized polyol cyclic ethers using a migratory ether formation strategy. In contrast to the common pathway of direct opening of epoxides, Me3Al was found to promote an unprecedented ether addition reaction, opening a neighboring epoxide. The resulting oxonium intermediate triggers a 1,3-methyl shift to yield 2-deoxyribital products. When the hemiacetal auxiliary is a monosaccharide, the sugar ring is expanded by four atoms to give the corresponding 9- to 11-membered analogues. This method provides an entry into the untapped chemical space of medium-sized sugar mimetics.
- Jiang, Hao,Xu, Li-Ping,Fang, Yan,Zhang, Zhen-Xing,Yang, Zhen,Huang, Yong
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- Mechanistic Details of Asymmetric Bromocyclization with BINAP Monoxide: Identification of Chiral Proton-Bridged Bisphosphine Oxide Complex and Its Application to Parallel Kinetic Resolution
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The mechanism of our previously reported catalytic asymmetric bromocyclization reactions using 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) monoxide was examined in detail by the means of control experiments, NMR studies, X-ray structure analysis, and CryoSpray electrospray ionization mass spectrometry (ESI-MS) analysis. The chiral BINAP monoxide was transformed to a key catalyst precursor, proton-bridged bisphosphine oxide complex (POHOP·Br), in the presence of N-bromosuccinimide (NBS) and contaminating water. The thus-formed POHOP further reacts with NBS to afford BINAP dioxide and molecular bromine (Br2) simultaneously in equimolar amounts. While the resulting Br2 is activated by NBS to form a more reactive brominating reagent (Br2─NBS), BINAP dioxide serves as a bifunctional catalyst, acting as both a Lewis base that reacts with Br2─NBS to form a chiral brominating agent (P═O+─Br) and also as a Br?nsted base for the activation of the substrate. By taking advantage of this novel concerted Lewis/Br?nsted base catalysis by BINAP dioxide, we achieved the first regio- and chemodivergent parallel kinetic resolutions (PKRs) of racemic unsymmetrical bisallylic amides via bromocyclization.
- Hamashima, Yoshitaka,Hirokawa, Ryo,Hisanaga, Tatsunari,Ichikawa, Mamoru,Kawato, Yuji,Nagao, Yoshihiro,Takita, Ryo,Watanabe, Kohei,Yamashita, Kenji
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p. 3913 - 3924
(2022/03/15)
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- Probing the Ca2+ mobilizing properties on primary cortical neurons of a new stable cADPR mimic
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Cyclic adenosine diphosphate ribose (cADPR) is a second messenger involved in the Ca2+ homeostasis. Its chemical instability prompted researchers to tune point by point its structure, obtaining stable analogues featuring interesting biological properties. One of the most challenging derivatives is the cyclic inosine diphosphate ribose (cIDPR), in which the hypoxanthine isosterically replaces the adenine. As our research focuses on the synthesis of N1 substituted inosines, in the last few years we have produced new flexible cIDPR analogues, where the northern ribose has been replaced by alkyl chains. Interestingly, some of them mobilized Ca2+ ions in PC12 cells. To extend our SAR studies, herein we report on the synthesis of a new stable cIDPR derivative which contains the 2″S,3″R dihydroxypentyl chain instead of the northern ribose. Interestingly, the new cyclic derivative and its open precursor induced an increase in intracellular calcium concentration ([Ca2+]i) with the same efficacy of the endogenous cADPR in rat primary cortical neurons.
- D'Errico, Stefano,Greco, Francesca,Patrizia Falanga, Andrea,Tedeschi, Valentina,Piccialli, Ilaria,Marzano, Maria,Terracciano, Monica,Secondo, Agnese,Roviello, Giovanni Nicola,Oliviero, Giorgia,Borbone, Nicola
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- Fischer Carbene Pentannulation with Alkynes Having Adjacent Carbonate or Acyloxy Groups: Synthesis of 3-Substituted 1-Indanones
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Various aryl Fischer carbenes reacted with alkynes having adjacent acyloxy or carbonate groups to regioselectively deliver 3-substituted 1-indanones. The acyloxy or carbonate group probably coordinates with the Cr metal to give a tetra-coordinated chromium complex forming a six-membered ring that retards CO insertion for ketene formation, which is required for benzannulation. Alternatively, the ortho position aryl ring attack results in pentannulation, providing regioselectively 3-substituted 1-indanones. The method is extended to the synthesis of the core structure of 3-epi-mutisianthol.
- Bhattacharyya, Shubhankar,Chavan, Vijay P.,Fernandes, Rodney A.,Gholap, Sachin P.,Saiyed, Akeel S.
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p. 3438 - 3443
(2020/04/20)
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- Ascaroside Signaling in the Bacterivorous Nematode Caenorhabditis remanei Encodes the Growth Phase of Its Bacterial Food Source
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A novel class of species-specific modular ascarosides that integrate additional fatty acid building blocks was characterized in the nematode Caenorhabditis remanei using a combination of HPLC-ESI-(-)-MS/MS precursor ion scanning, microreactions, HR-MS/MS, MSn, and NMR techniques. The structure of the dominating component carrying a cyclopropyl fatty acid moiety was established by total synthesis. Biogenesis of this female-produced male attractant depends on cyclopropyl fatty acid synthase (cfa), which is expressed in bacteria upon entering their stationary phase.
- Dolke, Franziska,Dong, Chuanfu,Bandi, Siva,Paetz, Christian,Glauser, Gaétan,Von Reu?, Stephan H.
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p. 5832 - 5837
(2019/08/26)
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- Stereoselective Access to the Core Structure of Macroline-Type Indole Alkaloids: Total Synthesis of Macroline and Alstomicine
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Rapid synthesis of the pentacyclic core structure of macroline-type indole alkaloids, and its application in the total synthesis of macroline and alstomicine is described. The core structure was accomplished in a highly stereocontrolled manner via two key steps, Ireland-Claisen rearrangement and Pictet-Spengler cyclization, commencing from a readily available starting material l-tryptophan, which obviated the need of a particular chiral source as an external catalyst, reagent, or internal auxiliary.
- Kadam, Vilas D.,Rao, Sridhara Shanmukha,Mahesh,Chakraborty, Mithun,Vemulapalli, S. Phani Babu,Dayaka, Satya Narayana,Sudhakar, Gangarajula
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supporting information
p. 4782 - 4786
(2018/08/24)
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- Synthesis of Cyclopropane Fatty Acids by C(sp3)?C(sp3) Cross-Coupling Reaction and Formal Synthesis of α-Mycolic Acid
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An iterative Ni-catalyzed C(sp3)?C(sp3) cross-coupling reaction of a novel cis-cyclopropane containing bifunctional building blocks with alkyl halides and alkyl Grignard reagents enabled the introduction of a cyclopropane ring into the desired position(s) of saturated carbon frameworks, providing a straightforward synthetic route to cyclopropane fatty acids. The present method creates a direct route for the construction of saturated carbon frameworks, and can avoid the tedious multistep operations based on unsaturated functional group manipulations that are often employed in conventional synthetic routes. This method could be applicable to the synthesis of trans-cyclopropane fatty acids and enantioenriched cyclopropane fatty acids. Formal synthesis of α-mycolic acid was achieved by the C(sp3)?C(sp3) cross-coupling reaction of cyclopropane-containing bifunctional building blocks. (Figure presented.).
- Iwasaki, Takanori,Terahigashi, Shohei,Wang, Yufei,Tanaka, Arisa,Zhao, Hanqing,Fujimoto, Yukari,Fukase, Koichi,Kambe, Nobuaki
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supporting information
p. 3810 - 3817
(2018/09/18)
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- Synthesis and Application of Stereoretentive Ruthenium Catalysts on the Basis of the M7 and the Ru-Benzylidene-Oxazinone Design
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A series of new stereoretentive ruthenium catalysts bearing the dithiocatecholate ligand was synthesiszed on the basis of the M7 and Ru-benzylidene-oxazinone design. The activity of the catalysts was tested in ring-opening cross-metathesis reactions, ring
- Dumas, Adrien,Müller, Daniel S.,Curbet, Idriss,Toupet, Lo?c,Rouen, Mathieu,Baslé, Olivier,Mauduit, Marc
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supporting information
p. 829 - 834
(2018/03/21)
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- Stereoretentive Olefin Metathesis Made Easy: In Situ Generation of Highly Selective Ruthenium Catalysts from Commercial Starting Materials
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The in situ preparation of highly stereoretentive ruthenium-based metathesis catalysts is reported. This approach completely avoids the isolation of intermediates and air-sensitive catalysts, thus allowing for the rapid access and evaluation of numerous dithiolate Ru catalysts. A procedure was established to perform cross-metathesis reactions without the use of a glovebox, and on a small scale even Schlenk techniques are not required. Consequently, the chemistry displayed in this report is available to every practicing organic chemist and presents a powerful approach for the identification of new stereoretentive catalysts.
- Müller, Daniel S.,Curbet, Idriss,Raoul, Yann,Le N?tre, Jér?me,Baslé, Olivier,Mauduit, Marc
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supporting information
p. 6822 - 6826
(2018/10/31)
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- Synthesis of Branched Alkylboronates by Copper-Catalyzed Allylic Substitution Reactions of Allylic Chlorides with 1,1-Diborylalkanes
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Reported herein is a copper-catalyzed SN2'-selective allylic substitution reaction using readily accessible allylic chlorides and 1,1-diborylalkanes, a reaction which proceeds with chemoselective C-B bond activation of the 1,1-diborylalkanes. I
- Kim, Junghoon,Park, Sangwoo,Park, Jinyoung,Cho, Seung Hwan
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supporting information
p. 1498 - 1501
(2016/02/14)
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- High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective cross-metathesis
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Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences. A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium-disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4-8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro-ruthenium complexes, indicating that its utility may extend beyond Z-selective processes.
- Koh, Ming Joo,Khan, R. Kashif M.,Torker, Sebastian,Yu, Miao,Mikus, Malte S.,Hoveyda, Amir H.
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p. 181 - 186
(2015/03/30)
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- CATALYSTS FOR EFFICIENT Z-SELECTIVE METATHESIS
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The present application provides, among other things, compounds and methods for metathesis reactions. In some embodiments, provided compounds promote highly efficient and highly Z-selective metathesis. In some embodiments, provided compounds and methods are particularly useful for producing allyl alcohols. In some embodiments, provided compounds have the structure of formula I. In some embodiments, provided compounds comprise ruthenium, and a ligand bonded to ruthenium through a sulfur atom.
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Paragraph 00613-00614; 00621-00622
(2015/01/09)
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- Anionic polycyclization entry to tricycles related to quassinoids and terpenoids: A stereocontrolled total synthesis of (+)-cassaine
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A full account of our anionic polycyclization approach to access highly functionalized tricycles related to quassinoids and terpenoids from several optically active bicyclic enone systems and Nazarov reagents is presented. (+)-Carvone is the only chiral s
- Ravindar, Kontham,Caron, Pierre-Yves,Deslongchamps, Pierre
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p. 7979 - 7999
(2015/03/18)
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- Intramolecular palladium mediated π-allyl cyclisation of bis-Cbz- and bis-Boc-protected guanidines
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The Pd-mediated π-allyl cyclisation of bis-Cbz- and bis-Boc-protected guanidines 4 and 14b led to the formation of five- and six-membered heterocycles 5 and 17 in high yields.
- Al-Shuhaib, Zainab,B?ckemeier, Henning,Coghlan, Lawrence,D?rksen, Elina,Jones, Iestyn V.,Murphy, Patrick J.,Nash, Robert,Page, James M.
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p. 6716 - 6718
(2013/11/19)
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- Enantiodivergent and γ-selective asymmetric allylic amination
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Double agent: The title reaction using the guanidine catalyst 1 can deliver both enantiomers of the product with excellent enantioselectivity by judicious choice of the double bond geometry of the the β,γ-unsaturated carbonyl compound. Computational studies reveal the possible origin of the inversed enantioselectivity, and the potential for enantiodivergent synthesis chiral amine-containing substrates is attractive. Copyright
- Wang, Jianmin,Chen, Jie,Kee, Choon Wee,Tan, Choon-Hong
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supporting information; experimental part
p. 2382 - 2386
(2012/05/19)
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- Sequencing cross-metathesis and non-metathesis reactions to rapidly access building blocks for synthesis
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The olefin cross-metathesis reaction has been sequenced with four common organic transformations in a one- or two-pot manner to rapidly access useful building blocks. Those reactions are: (1) phosphorus-based olefination (e.g., Wittig and Horner-Wadsworth-Emmons); (2) hydride reduction; (3) Evans propionate aldol reaction; (4) Brown allyl- and Roush crotyl-boration. The products of these reactions include stereodefined 2,4-dienoates, trans allylic alcohols, syn-propionate aldols, and chiral non-racemic homoallylic alcohols, respectively. Many of these intermediates have been carried further to natural products, demonstrating the utility of the methodology.
- Sirasani, Gopal,Paul, Tapas,Andrade, Rodrigo B.
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p. 2197 - 2205
(2011/04/22)
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- The use of COP-OAc in the catalyst-controlled syntheses of 1,3-polyols
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An iterative strategy to the 1,3-polyol motif is described. The use of the catalytic asymmetric Overman esterification for the construction of all stereogenic centers is broadly examined as are the sequences to extend the developing polyol chain. The iterative strategies are applied to the total syntheses of rugulactone and polyrhacitides A and B. 1 Introduction 2 Results and Discussion 2.1 Chain Elongation via RCM (Cycle A) 2.2 Total Synthesis of Rugulactone 2.3 Chain Elongation via Ando Olefination (Cycle B) and Total Syntheses of Polyrhacitides A and B 2.4 Useful Variants 3 Conclusions. Georg Thieme Verlag Stuttgart. New York.
- Kirsch, Stefan F.,Klahn, Philipp,Menz, Helge
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p. 3592 - 3603
(2011/12/21)
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- Total synthesis of largazole
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The stereocontrolled total synthesis of largazole was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction, thiazoline-thiazole formation, and macrolactamization by use of the Mukaiyama reagent. Georg Thieme Verlag Stuttgart.
- Ren, Qi,Dai, Lu,Zhang, Hui,Tan, Wenfei,Xu, Zhengshuang,Ye, Tao
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body text
p. 2379 - 2383
(2009/05/27)
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- One-pot sequential cross-metathesis/hydride reduction: highly stereoselective synthesis of primary (E)-allylic alcohols from terminal olefins
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Several di- and trisubstituted primary (E)-allylic alcohols have been prepared from the corresponding terminal olefins in a highly stereoselective manner (>20:1 E/Z) by sequencing olefin cross-metathesis (CM) with hydride reduction (DIBAL-H) in good yields utilizing only commercially available reagents in a one-pot fashion. The method is a reliable alternative to the direct CM of terminal olefins with allyl alcohol, which is not always stereoselective but rather highly substrate dependent.
- Paul, Tapas,Sirasani, Gopal,Andrade, Rodrigo B.
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p. 3363 - 3367
(2008/09/21)
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- Palladium-catalyzed aryl amination-heck cyclization cascade: A one-flask approach to 3-substituted indoles
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(Chemical Equation Presented) Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation of a single indole regioisomer, which can be functionalized in situ by N-arylation (see scheme). dba = dibenzylideneacetone, dppf = 1,1′-bis(diphenylphospanyl)ferrocene.
- Jensen, Thomas,Pedersen, Henrik,Bang-Andersen, Benny,Madsen, Robert,Jorgensen, Morten
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p. 888 - 890
(2008/09/20)
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- CRYSTALLINE SOLID FORM OF (2S-5Z)-2-AMINO-7-(ETHANIMIDOYLAMINO)-2-METHYLHEPT-5-ENOIC ACID
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(2S,5Z)-2-amino-7-(ethanimidoylamino)-2-methylhept-5-enoic acid is crystallized as an anhydrous, stoichiometric 1.5 HCl salt and a scaleable crystallization method is disclosed. The salt form was characterized and the absolute configuration of the chiral
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- Palladium(II)-catalyzed stereocontrolled cyclization via hemiacetal intermediates: Total synthesis of 5-epi-prelactone C
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Palladium(II)-catalyzed cyclization of 3,7-dihydroxy-4-methyl-5-octenal derivative was carried out to give 2,3,4,6-tetrasubstituted tetrahydropyran with stereoselective 1,3-chirality transfer in net retention of stereochemistry. The cyclized product was c
- Miyazawa, Masahiro,Narantsetseg, Magsarjav,Yokoyama, Hajime,Yamaguchi, Seiji,Hirai, Yoshiro
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p. 1017 - 1021
(2007/10/03)
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- Regiochemical control of the ring opening of 1:2-epoxides by means of chelating processes. 10. Synthesis and ring opening reactions of mono- and difunctionalized cis and trans aliphatic oxirane systems
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The regiochemical outcome of the ring opening of 1:2-epoxides through chelation processes assisted by metal ions, was verified in mono- and difunctionalized aliphatic oxirane systems bearing the heterofunctionality (OR) in an homoallylic and/or allylic relationship to the oxirane ring. The effect of the distance of the OR functionality from the oxirane ring and of the type of protective group on the regiochemical outcome of these systems is examined. In some cases, the use of LiClO4 or Mg(ClO4)2 as the promoting metal salt makes it possible the obtainment of a nice regioalternating process.
- Azzena, Francesca,Calvani, Federico,Crotti, Paolo,Gardelli, Cristina,Macchia, Franco,Pineschi, Mauro
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p. 10601 - 10626
(2007/10/02)
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- The first enantiocontrolled synthesis of (3S,8S)-(-)-4,6-decadiyne-1,3,8-triol isolated from a toxic mushroom Gymnopilus spectabilis
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The first synthesis of (3S,8S)-(-)-4,6-decadiyne-1,3,8-triol, isolated from a toxic mushroom Gymnopilus spectabilis, has been achieved by employing the chiral 3-hydroxyalkyne formation reaction as the key step.
- Takano,Sugihara,Ogasawara
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p. 2797 - 2798
(2007/10/02)
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- Total Synthesis of the Sesterterpenoid (+/-)-Palauolide
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Transformation of 3,6-dimethylcyclohex-2-enone (2) into the sesterterpenoid (+/-)-palauolide (1) was accomplished via a 17-step sequence of reactions.
- Piers, Edward,Wai, John S. M.
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p. 1342 - 1343
(2007/10/02)
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