- Stereoselective synthesis of the C1-C12 fragment of the cytotoxic macrolide FD-891
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A stereoselective synthesis of the C1-C12 fragment of the naturally occurring, cytotoxic macrolide FD-891, is described. The initial chirality was created via an asymmetric Evans aldol reaction. Two other asymmetric reactions, a Sharpless epoxidation and
- Murga, Juan,García-Fortanet, Jorge,Carda, Miguel,Marco, J. Alberto
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- Design and synthesis of pironetin analogues with simplified structure and study of their interactions with microtubules
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The preparation of a series of pironetin analogues with simplified structure is described. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that, while less active than the parent molecule, the pironetin analogues still share the mechanism of action of the latter and compete for the same binding site to α-tubulin. Variations in the configurations of their stereocenters do not translate into relevant differences between biological activities.
- Marco, J. Alberto,García-Pla, Jorge,Carda, Miguel,Murga, Juan,Falomir, Eva,Trigili, Chiara,Notararigo, Sara,Díaz, J. Fernando,Barasoain, Isabel
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- Stereoselective synthesis of (-)-galantinic acid
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An efficient and highly concise synthesis of (-)-galantinic acid has been achieved using an asymmetric allylation reaction of Garner's aldehyde. Georg Thieme Verlag Stuttgart - New York.
- Dubey, Abhishek,Harbindu, Anand,Kumar, Pradeep
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- Total syntheses of (-)-macrolactin a, (+)-macrolactin e, and (-)- macrolactinic acid: An exercise in stille cross-coupling chemistry
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The total syntheses of the potent antiviral agent (-)-macrolactin A (1) and two related family members, (+)-macrolactin E (5) and (-)-macrolactinic acid (7), have been achieved, exploiting a unified, convergent, and highly stereocontrolled strategy. Extensive use of the palladium-catalyzed Stille cross-coupling reaction for the stereospecific construction of the three isolated dienes including macrocyclization formed the cornerstone of the successful strategy. The total syntheses of these natural products, no longer available via fermentation, confirm their relative and absolute stereochemistries and provide access to possible analogues for further biological study.
- Smith III, Amos B.,Ott, Gregory R.
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- Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies
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A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.
- Novaes, Luiz F.T.,Sarotti, Ariel M.,Pilli, Ronaldo A.
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- Studies toward the Total Synthesis of Caribbean Ciguatoxin C-CTX-1: Synthesis of the LMN-Ring Fragment through Reductive Olefin Cross-Coupling
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Synthesis of the LMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the principal causative toxin for ciguatera fish poisoning around the Caribbean Sea areas, is described. The key feature of the synthesis is the stereoselective introduction of an angular methyl group on the sterically encumbered seven-membered M-ring by the application of a hydrogen atom transfer-based reductive olefin coupling.
- Sasaki, Makoto,Iwasaki, Kotaro,Arai, Keisuke
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- Enantioselective Total Synthesis of Diocollettines A
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The first enantioselective total synthesis of diocollettines A was accomplished in only six steps from a known compound. A short and practical synthetic route was disclosed, featuring an intensive investigation of the stereoselective aldol reaction as a key step using an easily prepared aldehyde moiety and an enone derivative. The synthetic scheme also includes the efficient stereocontrolled construction of the tricyclic skeleton of diocollettines A by intramolecular acetal formation, stereoselective dihydroxylation, and intramolecular ether cyclization.
- Kawamoto, Yuichiro,Kobayashi, Toyoharu,Ito, Hisanaka
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supporting information
p. 5813 - 5816
(2019/07/08)
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- Total synthesis and configurational assignment of the marine natural product haliclamide
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The marine natural product haliclamide has been synthesized based on macrocyclization by ring-closing olefin metathesis. Using either enantiomer of two of the four building blocks that were employed to assemble the diene precursor for the metathesis reaction, three non-natural isomers of haliclamide were also prepared. On the basis of the comparison of the 1H and 13C NMR spectra of the individual stereoisomers with literature data for the natural product, the configuration of the previously unassigned stereocenters at C9 and C20 of haliclamide could be determined to be S for both carbons. The absolute configuration of haliclamide thus is 2S, 9S, 14R, 20S. The antiproliferative activity of synthetic haliclamide against several human cancer cell lines was found to be in the high μM range. The compound showed no antifungal or antibiotic activity.
- Pfeiffer, Bernhard,Speck-Gisler, Sandra,Barandun, Luzi,Senft, Ursula,De Groot, Claire,Lehmann, Irene,Ganci, Walter,Gertsch, Juerg,Altmann, Karl-Heinz
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p. 2553 - 2563
(2013/05/22)
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- Studies on C18-C20 aldol couplings of rhizopodin
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The aldol addition of an enol(ate) to a carbonyl compound is one of the most powerful and versatile C-C bond forming reactions. In complex target synthesis the coupling of two chiral partners may complicate the stereochemical outcome by multiple stereoinductions. Here, we report studies on pivotal aldol couplings employed in the rhizopodin synthesis, detailing the various directing effects exerted by the stereogenic centers present in this sterically hindered connection. Georg Thieme Verlag Stuttgart. New York.
- Dieckmann, Michael,Rudolph, Sven,Lang, Carolin,Ahlbrecht, Wiebke,Menche, Dirk
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p. 2305 - 2315
(2013/09/02)
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- Synthesis and pharmacological properties of 5-alkyl substituted nicotine analogs
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This paper describes a concise and practical route to enantiomerically enriched 5-alkyl substituted nicotine analogs. The Vilsmeier reaction was used to construct the nicotinaldehydes ring followed by the introduction of the chiral homoallylic alcohol by organic boron reagent and the cyclization of the pyrrolidine ring through the reduction of a chiral azide. 17 analogs have been synthesized and their corresponding biological activities were tested, in which compounds 10d and 10g exhibit excellent IC50 values against RD and SY-SY5Y. Copyright
- Wang, Jing,Li, Xi,Yuan, Qianjia,Ren, Jiangmeng,Huang, Jin,Zeng, Bubing
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p. 2813 - 2818
(2013/08/23)
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- Total synthesis of (+)-SCH 351448
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A convergent synthesis of (+)-SCH 351448 (1), a monosodium salt of a C 2-symmetric macrodiolide, is described. Our approach is based on a [4 + 2] annulation with a chiral allyl silane (anti-5c) to assemble the pyran subunits. Homodimerization w
- Zhu, Kaicheng,Panek, James S.
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supporting information; experimental part
p. 4652 - 4655
(2011/11/06)
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- Peloruside B, a potent antitumor macrolide from the New Zealand marine sponge Mycale hentscheli: Isolation, structure, total synthesis, and bioactivity
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(Chemical Equation Presented) Peloruside B(2), a natural congener of pelorusideA(1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G2/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation.
- Singh, A. Jonathan,Xu, Chun-Xiao,Xu, Xiaoming,West, Lyndon M.,Wilmes, Anja,Chan, Ariane,Hamel, Ernest,Miller, John H.,Northcote, Peter T.,Ghosh, Arun K.
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supporting information; experimental part
p. 2 - 10
(2010/04/26)
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- A versatile Enantioselective Synthesis of Barrenazines
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A versatile enantioselectlve total synthesis of barrenazines A and B has been accomplished from 1,4-butanediol. The key steps of the synthesis are a sequential allylboration/rlng-closing metathesis for the construction of the tetrahydropyrldlne ring and t
- Pena-Lopez, Miguel,Montserrat Martinez,Sarandeses, Luis A.,Sestelot, Jose Perez
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supporting information; experimental part
p. 852 - 854
(2010/04/29)
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- Convergent, stereoselective syntheses of the glycosidase inhibitors broussonetines D and M
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The first syntheses of the polyhydroxylated alkaloids (iminosugars) broussonetines D and M, glycosidase inhibitors of the pyrrolidine class, have been performed in a convergent, stereocontrolled way from d-serine as the chiral starting material. A cross m
- Ribes, Celia,Falomir, Eva,Murga, Juan,Carda, Miguel,Alberto Marco
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supporting information; experimental part
p. 1355 - 1360
(2009/12/04)
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- Design and synthesis C6-C8 bridged epothilone a
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A conformationally restrained epothilone A analogue (3) with a short bridge between methyl groups at C6 and C8 was designed and synthesized. Preliminary biological evaluation indicates 3 to be only weakly active (IC50 = 8.5 μM) against the A2780 human ovarian cancer cell line.
- Zhan, Weiqiang,Jiang, Yi,Brodie, Peggy J.,Kingston, David G. I.,Liotta, Dennis C.,Snyder, James P.
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supporting information; experimental part
p. 1565 - 1568
(2009/04/10)
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- Total synthesis of 27-hydroxy-bullatacin and its C-15 epimer, and studies on their inhibitory effect on bovine heart mitochondrial complex I functions
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The total synthesis of 27-hydroxybullatacin and its C-15 epimer has been achieved using rhenium(VII) oxides-mediated and Co(modp)2-catalyzed oxidative cyclization (OC), diastereoselective alkynylation, Brown's enantioselective allylboration, an
- Chen, Zhiyong,Sinha, Subhash C.
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p. 1603 - 1611
(2008/09/17)
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- Alternative and expedient asymmetric syntheses of L-(+)-Noviose
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(Chemical Equation Presented) L-(+)-Noviose, the sugar component of the antibiotic novobiocin, was synthesized from readily available non-carbohydrate starting materials relying on stoichiometric and asymmetric processes by two independent methods, compri
- Hanessian, Stephen,Auzzas, Luciana
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p. 261 - 264
(2008/09/19)
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- Enantioselective total synthesis of peloruside a: A potent microtubule stabilizer
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An enantioselective total synthesis of (+)-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A.
- Ghosh, Arun K.,Xu, Xiaoming,Kim, Jae-Hun,Xu, Chun-Xiao
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supporting information; experimental part
p. 1001 - 1004
(2009/04/07)
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- syn-1,2-amino alcohols via diastereoselective allylic C-H amination
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A novel Pd/sulfoxide catalyzed diastereoselective allylic C-H amination reaction of chiral homoallylic N-tosyl carbamates is reported. Densely oxygenated ∞-olefin substrates with multiple stereogenic centers undergo allylic C-H amination in excellent yiel
- Fraunhoffer, Kenneth J.,White, M. Christina
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p. 7274 - 7276
(2008/02/06)
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- Asymmetrie total syntheses of two phlegmarine-type alkaloids, lycoposerramines-V and -W, newly isolated from lycopodium serratum
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Two new Phlegmarine-type alkaloids, lycoposerramines-V and -W, were isolated from Lycopodium serratum, and their structures including the absolute configuration were established by asymmetric total synthesis involving such key steps as Johnson-Claisen rea
- Shigeyama, Takahide,Katakawa, Kazuaki,Kogure, Noriyuki,Kitajima, Mariko,Takayama, Hiromitsu
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p. 4069 - 4072
(2008/02/11)
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- The total synthesis and biological properties of the cytotoxic macrolide FD-891 and its non-natural (Z)-C12 isomer
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A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD-891 and of its non-natural (Z)-C12 isomer is described. Three fragments of the main carbon chain were stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia-Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12-C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be cleared.
- Garcia-Fortanet, Jorge,Murga, Juan,Carda, Miguel,Marco, J. Alberto,Matesanz, Ruth,Diaz, J. Fernando,Barasoain, Isabel
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p. 5060 - 5074
(2008/02/11)
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- Total synthesis and absolute configuration determination of (+)-bruguierol C
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(Chemical Equation Presented) The first total synthesis and absolute configuration of bruguierol C are reported. The key step involved the diastereoselective capture of an in situ generated oxocarbenium ion via an intramolecular Friedel-Crafts alkylation.
- Solorio, Dionicio Martinez,Jennings, Michael P.
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p. 6621 - 6623
(2008/02/10)
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- Antiparasite and antimycobacterial activity of passifloricin analogues
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Several structural analogues of the polyketide passifloricin lactone were synthesized using asymmetric stereoselective allylations and ring-closing methateses as key reactions. These compounds were active in vitro against intracellular amastigotes of Leishmania panamensis (strain UA140), trophozoites of Plasmodium falciparum (strain NF54), and Mycobacterium tuberculosis (strain H37Rv). However, in spite of the significative antiparasitic activity of some synthetic analogues a high cytotoxicity was also observed. Based on these results a lactam derivative was also synthesized. This compound maintained a good level of activity with less toxicity.
- Cardona, Wilson,Qui?ones, Winston,Robledo, Sara,Vélez, Ivan Darío,Murga, Juan,García-Fortanet, Jorge,Carda, Miguel,Cardona, Diana,Echeverri, Fernando
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p. 4086 - 4092
(2007/10/03)
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- Synthesis of the C29-C37 bicyclic ether core of (+)-sorangicin A
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(Chemical Equation Presented) Construction of the unique bicyclic bis-ether core of the macrolide (+)-sorangicin A has been achieved. This fragment was prepared by utilizing a one-pot cascade of three bond forming events. An epoxide opening of the epoxy tosylate 2 led to the formation of the tetrahydropyran and subsequently to a second epoxide. Finally, a second epoxide opening closed the tetrahydrofuran ring. The bicyclic fragment was synthesized in just nine steps from (E)-cinnamaldehyde.
- Crimmins, Michael T.,Haley, Matthew W.
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p. 4223 - 4225
(2007/10/03)
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- Stereoselective synthesis of the monomeric unit of SCH 351448
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The monomeric unit of the macrodiolide SCH 351448 has been synthesized from three building blocks. Strategic disconnections were chosen between C21-C22 (Wittig) and C10-C11 (stereoselective aldol). The cis configuration of both 2,6-disubstituted tetrahydropyran rings was established by a stereoselective cationic reduction. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Backes, J. Rene,Koert, Ulrich
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p. 2777 - 2785
(2007/10/03)
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- Synthesis of iso-epoxy-amphidinolide N and des-epoxy-caribenolide i structures. Initial forays
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Two strategies for the projected total synthesis of the phenomenally potent antitumour macrolides amphidinolide N (1) and caribenolide I (2) are described. The title compounds are introduced as challenging and unique targets for chemical synthesis, and their retrosynthetic analysis is presented. The synthesis of the four defined key building blocks (10, 39, 67 and 72), required for the construction of amphidinolide N (1), in their enantiomerically pure forms, is described, followed by the coupling of 10, 39 and 72 through hydrazone alkylation processes to generate the complete C6-C29 carbon framework of the target compound (1). Fusion of the remaining C1-C5 sector (72) onto the molecule by metathesis-based methods was unsuccessful, resulting in the adoption of a second-generation strategy which called for the employment of one of the array of palladium-catalysed cross-coupling reactions to generate the C5-C6 carbon-carbon bond. Vinyl bromide 125, representing the C6-C29 skeleton of caribenolide I (2), was prepared through the sequential alkylation of hydrazone 10 with bromide 116 and iodide 55, but failed to engage in the appropriate cross-coupling reaction with a variety of C1-C4 partners. Despite these setbacks, the information gleaned from these endeavours was to prove invaluable in laying the foundation for the eventual successful approach to the macrocyclic structures of amphidinolide N (1) and caribenolide I (2). The Royal Society of Chemistry 2006.
- Nicolaou,Brenzovich, William E.,Bulger, Paul G.,Francis, Tasha M.
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p. 2119 - 2157
(2008/02/07)
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- Stereoselective synthesis of the naturally occurring styryllactones (+)-goniofufurone and (+)-cardiobutanolide
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(Chemical Equation Presented) The naturally occurring γ-lactones (+)-goniofufurone 1 and (+)-cardiobutanolide 2, two pharmacologically active products from Goniothalamus species (Annonaceae), have been synthesized in enantiopure form using L-erythrulose a
- Ruiz, Purificacion,Murga, Juan,Carda, Miguel,Marco, J. Alberto
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p. 713 - 716
(2007/10/03)
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- Role of the A-ring of bryostatin analogues in PKC binding: Synthesis and initial biological evaluation of new A-ring-modified bryologs
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(Chemical Equation Presented) The syntheses of three newly designed bryostatin analogues are reported. These simplified analogues, which lack the A-ring present in the natural product but possess differing groups at C9, were obtained using a divergent app
- Wender, Paul A.,Clarke, Michael O.,Horan, Joshua C.
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p. 1995 - 1998
(2007/10/03)
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- Hydrocarbon oxidation vs C-C bond-forming approaches for efficient syntheses of oxygenated molecules
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(Chemical Equation Presented) A hydrocarbon oxidation approach has been applied to the construction of several linear (E)-allylic alcohols that have served as intermediates in the synthesis of natural products and natural product-like molecules. In the original syntheses, these intermediates were constructed using a standard Wittig-type olefination approach. We report here that routes to these same intermediates designed around a hydrocarbon oxidation approach are more efficient both in the total number of functional group manipulations (FGMs) and overall steps, as well as in the overall yield.
- Fraunhoffer, Kenneth J.,Bachovchin, Daniel A.,White, M. Christina
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p. 223 - 226
(2007/10/03)
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- Application of the Doetz reaction to construction of a major portion of the ansa macrocycle (-)-kendomycin
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(Chemical Equation Presented) A Doetz reaction employing a terminal alkyne and a Fischer-type alkenylchromium carbenoid led to a pentasubstituted benzene from which a major portion of the Streptomyces metabolite (-)-kendomycin was synthesized.
- White, James D.,Smits, Helmars
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p. 235 - 238
(2007/10/03)
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- Synthesis of novel, simplified, C-7 substituted eleutheside analogues with potent microtubule-stabilizing activity
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The synthesis of a number of novel, simplified, C-7 substituted eleutheside analogues with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring closing metathesis as the key-step for obtaining the 6-10 fused bicyclic r
- Castoldi, Damiano,Caggiano, Lorenzo,Bayón, Pau,Costa, Anna M.,Cappella, Paolo,Sharon, Ofer,Gennari, Cesare
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p. 2123 - 2139
(2007/10/03)
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- Efficient asymmetric synthesis of (+)-SCH 351448
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(Chemical Equation Presented) An efficient and stereocontrolled total synthesis of (+)-SCH 351448, a novel activator of low-density lipoprotein receptor promoter, has been achieved with a longest linear sequence of 21 steps. Key steps include applications
- Bolshakov, Sergei,Leighton, James L.
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p. 3809 - 3812
(2007/10/03)
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- The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: The CD-spiroacetal segment
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Stereocontrolled syntheses of the C16-C28 CD-spiroacetal subunit of altohyrtin A/spongistatin 1 (1), relying on kinetic and thermodynamic control of the spiroacetal formation, are described. The kinetic control approach resulted in a slight preference (60: 40) for the desired spiroacetal isomer. The thermodynamic approach allowed ready access to the desired spiroacetal 2 by acid-promoted equilibration, Chromatographic separation of the C23 epimers and resubjection of the undesired isomer to the equilibration conditions. This scalable synthetic sequence provided multi-gram quantities of 2, thus enabling the successful completion of the total synthesis of altohyrtin A/spongistatin 1, as reported in Part 4 of this series. The Royal Society of Chemistry 2005.
- Paterson, Ian,Coster, Mark J.,Chen, David Y.-K.,Gibson, Karl R.,Wallace, Debra J.
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p. 2410 - 2419
(2007/10/03)
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- Diastereoselective synthesis of the acyl side-chain and amino acid (2S,3R)-3-hydroxy-3-methylproline fragments of polyoxypeptin A
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Synthesis of the acyl side-chain and amino acid (2S,3R)-3-hydroxy-3- methylproline units of the potent depsipeptide polyoxypeptin A, is described. Key intermediates were secured via diastereoselective addition involving a homoenolate ion and allylation of
- Chen, Zhiyong,Ye, Tao
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p. 2781 - 2785
(2007/10/03)
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- Synthesis of rimocidinolide methyl ester, the aglycone of (+)-rimocidin
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An efficient, convergent route based on cyanohydrin acetonide couplings was used for the synthesis of the aglycone of rimocidin, rimocidinolide methyl ester (1). Cyanohydrin acetonides were used as β-hydroxyketone synthetic equivalents in the assembly of the polyol chain.
- Packard, Garrick K.,Hu, Yueqing,Vescovi, Andrea,Rychnovsky, Scott D.
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p. 2822 - 2826
(2007/10/03)
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- Total synthesis of (+)-brasilenyne. Application of an intramolecular silicon-assisted cross-coupling reaction
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The first enantioselective total synthesis of (+)-brasilenyne (1) has been achieved in 19 linear steps, with 5.1% overall yield from L-(S)-malic acid. The construction of the oxonin core containing a 1,3-cis, cis diene unit was accomplished with a tandem ring-closing metathesis/silicon-assisted intramolecular cross-coupling reaction. In addition, a key propargylic stereogenic center was created through a novel, highly diastereoselective ring opening of a 1,3-dioxolanone promoted by TiCl4. This reaction proceeded through an oxocarbenium ion intermediate and the asymmetric induction was fully controlled by L-malic acid residue. The C(8) stereogenic center was set by a reagent-controlled asymmetric allylboration.
- Denmark, Scott E.,Yang, Shyh-Ming
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p. 12432 - 12440
(2007/10/03)
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- Convergent highly stereoselective preparation of the C12-C24 fragment of macrolactin A
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The convergent synthesis of the C12-C24 fragment (lower part) of macrolactin A is described. The adapted strategy allowed building up the lower moiety by the assembly of three key intermediates via organometallic addition. One hydroxylic stereogenic cente
- Bonini, Carlo,Chiummiento, Lucia,Pullez, Maddalena,Solladie, Guy,Colobert, Francoise
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p. 5015 - 5022
(2007/10/03)
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- Enantioselective total synthesis of borrelidin
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The first total synthesis of the natural product borrelidin is described. The propionate fragment of the molecule was concisely synthesized through catalytic enantioselective reductive aldol reactions, a catalytic Negishi coupling, and a catalytic directed hydrogenation. The propionate segment was then fused to the vinyl iodide fragment through a catalytic Sonogashira coupling. Subsequent catalytic hydrostannylation and catalytic cyanation allowed access to the target structure. Copyright
- Duffey, Matthew O.,LeTiran, Arnaud,Morken, James P.
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p. 1458 - 1459
(2007/10/03)
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- Synthesis of polyketides via diastereoselective acetalization
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(Matrix presented) Diastereoselective acetalization of pseudo-C 2-symmetric 1,3,5-triol systems is a general strategy for the rapid generation of polyketides. The oxidative acetalization reaction shown above was studied under both kinetic and t
- Shepherd, Jennifer N.,Myles, David C.
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p. 1027 - 1030
(2007/10/03)
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- Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp.
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A convergent total synthesis of phorboxazole A (1a), from the C(3-19), C(20-27) and C(33-46) fragments 5, 4 and 91, respectively, concentrating on stereocontrolled formation of the bonds at C(2-3), C(19-20) and C(27-28), is described. Although a coupling reaction between a macrolide ketone and the side chain substituted sulfone, at C(27-28) was not successful, a Wadsworth-Emmons olefination involving the oxane methyl ketone 4 and an oxazole produced the oxane 90 which was next coupled to 91 leading to the C(20-46) unit 100. A further coupling of 100 to 71c at C(19-20) then led to 105, ultimately, and the synthesis was completed by a macrocyclisation reaction from 105, at the C(2-3) alkene bond, followed by deprotection of 106.
- Pattenden, Gerald,Gonzalez, Miguel A,Little, Paul B,Millan, David S,Plowright, Alleyn T,Tornos, James A,Ye, Tao
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p. 4173 - 4208
(2007/10/03)
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- Enantioselective reduction of heteroaromatic β,γ-unsaturated ketones as an alternative to allylboration of aldehydes. Application: Asymmetric synthesis of SIB-1508Y
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Enantioselective reduction of heteroaromatic β,γ-unsaturated ketones was found to be an efficient and convenient alternative to the allylboration of corresponding aldehydes. This new method was used for the formal asymmetric synthesis of SIB-1508Y 2.
- Felpin, Fran?ois-Xavier,Bertrand, Marie-Jo,Lebreton, Jacques
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p. 7381 - 7389
(2007/10/03)
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- A highly stereoselective asymmetric synthesis of (-)-lobeline and (-)-sedamine
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A highly stereoselective asymmetric synthesis of (-)-sedamine and (-)-lobeline is described from benzaldehyde in 16 and 17 steps with an overall yield of 20% and 14%, respectively. The key intermediate syn-3,4-epoxyalcohol was prepared in a highly diastereomeric fashion (>99% ee, dr) and served as a common intermediate for both alkaloids.
- Felpin, Francois-Xavier,Lebreton, Jacques
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p. 9192 - 9199
(2007/10/03)
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- Intramolecular silicon-assisted cross-coupling: Total synthesis of (+)-brasilenyne
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The first, total synthesis of (+)-brasilenyne (1) has been achieved in 19 steps from l-(S)-malic acid. The key elements of this approach are a highly diastereoselective ring-opening of a 1,3-dioxolanone with bis(trimethylsilyl)acetylene) promoted by TiCl
- Denmark, Scott E.,Yang, Shyh-Ming
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p. 15196 - 15197
(2007/10/03)
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- Synthesis of the side chain of a novel carbapenem via iodine-mediated oxidative cyclization of (1R)-N-(1-aryl-3-butenyl)acetamide.
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A (2R,4S)-trans-disubstituted pyrrolidine ring system was constructed by employing iodine-mediated oxidative cyclization of (1R)-N-[1-(4-bromophenyl)-3-butenyl]acetamide 3 as a key step. The resulting diastereomeric mixture of (2R)-2-aryl-4-acetoxypyrroli
- Hashihayata, Takashi,Sakoh, Hiroki,Goto, Yasuhiro,Yamada, Koji,Morishima, Hajime
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p. 423 - 425
(2007/10/03)
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- Total synthesis of (+)-curacin A, a novel antimitotic metabolite from a cyanobacterium
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A concise total synthesis of (+)-curacin A, a potent antimitotic agent isolated from the cyanobacterium Lyngbya majuscula, is described. The synthesis features a new strategy to the 2-cyclopropyl-4-alkenyl substituted thiazoline unit in the natural product involving facile and selective thioacylation of the amino-alcohol 10 with the benzotriazole derived thioamide 11, leading to 28, as a key step. Cyclodehydration of 28 using Burgess' reagent then completed the synthesis of curacin A 1.
- Muir, James C.,Pattenden, Gerald,Ye, Tao
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p. 2243 - 2250
(2007/10/03)
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- Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco
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An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azidobut-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine I (5 steps, with an overall yield of 70%), (S)-hicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).
- Felpin,Girard,Vo-Thanh,Robins,Villieras,Lebreton
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p. 6305 - 6312
(2007/10/03)
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- The synthesis of an exhaustively stereodiversified library of cis-1,5 enediols by silyl-tethered ring-closing metathesis.
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[reaction: see text] This report describes the parallel synthesis of all 16 stereoisomers of the cis-1,5 enediol module 1. Compounds 1 derive from 2 by silicon-tethered ring-closing metathesis. Such libraries of stereodiversified ligands provide a unique
- Harrison,Verdine
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p. 2157 - 2159
(2007/10/03)
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- Stereoselective total synthesis of reveromycin B and C19-epi-reveromycin B
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Our studies toward the total synthesis of the reveromycin family of natural products are described herein. Our synthetic approach is efficient, stereocontrolled, and convergent and has resulted in the first synthesis of reveromycin B (4) and C19-epi-reveromycin B (55). Key steps of this successful strategy include: a modified Negishi coupling (construction of C7-C8 bond) and a Kishi-Nozaki reaction (construction of C19-C20 bond), which were employed in the attachment of the target side chains. The key building blocks for the total synthesis were thus defined as vinyl iodide 6, alkyne 7, and alkyne 8. Our synthesis illustrates the utility of the modified Negishi coupling for the construction of complex dienes, confirms the proposed stereochemistry of reveromycins and paves the way for the preparation of designed analogues for biological study.
- Drouet, Keith E.,Theodorakis, Emmanuel A.
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p. 1987 - 2001
(2007/10/03)
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