- Total Synthesis of Kalimantacin A
-
The kalimantacins make up a family of hybrid polyketide-nonribosomal peptide-derived natural products that display potent and selective antibiotic activity against multidrug resistant strains of Staphylococcus aureus. Herein, we report the first total synthesis of kalimantacin A, in which three fragments are prepared and then united via Sonogashira and amide couplings. The enantioselective synthetic approach is convergent, unlocking routes to further kalimantacins and analogues for structure-activity relationship studies and clinical evaluation.
- Davies, Jonathan A.,Bull, Freya M.,Walker, Paul D.,Weir, Angus N. M.,Lavigne, Rob,Masschelein, Joleen,Simpson, Thomas J.,Race, Paul R.,Crump, Matthew P.,Willis, Christine L.
-
supporting information
p. 6349 - 6353
(2020/09/02)
-
- A Method for the Stereoselective Construction of the Hemiaminal Center in Zampanolides
-
We have developed a new method for the stereoselective establishment of the N-acyl hemiaminal moiety in zampanolide-type structures that involves the reaction of (Z,E)-sorbamide (3) with BINAL-H and subsequent amide transfer from a putative aluminum carbo
- Brütsch, Tobias M.,Berardozzi, Simone,Rothe, Marlene L.,Horcajo, Mariano Redondo,Diáz, José Fernando,Altmann, Karl-Heinz
-
supporting information
p. 8345 - 8348
(2020/11/03)
-
- A Synthesis Strategy for the Production of a Macrolactone of Gulmirecin A via a Ni(0)-Mediated Reductive Cyclization Reaction
-
A synthesis strategy for the production of a key synthetic intermediate of gulmirecin A was described. The key reaction in the preparation of the 12-membered macrolactone is the Ni(0)-mediated reductive cyclization reaction of ynal using an N-heterocyclic carbene ligand and silane reductant. In addition, the α-selective glycosylation reaction of the macrolactone was performed to demonstrate the synthesis of gulmirecin and disciformycin precursors.
- Ichikawa, Satoshi,Katsuyama, Akira,Kitahata, Shun
-
supporting information
(2020/03/30)
-
- Exploration of the structure–activity relationship and druggability of novel oxazolidinone-based compounds as Gram-negative antibacterial agents
-
To gain further knowledge of the structure–activity relationship and druggability of novel oxazolidinone-based UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibitors as Gram-negative antibacterial agents, compounds containing the hydrophobic tails
- Ding, Shi,Ji, Jing-Chao,Zhang, Ming-Juan,Yang, Yu-She,Wang, Rui,Zhu, Xing-Long,Wang, Li-Hong,Zhong, Yi,Gao, Le,Lu, Man,Liu, Ju,Chen, Ye
-
-
- Organozinc-aided, HMPA-free, stoichiometric three-component coupling for the general synthesis of prostaglandins and stable prostacyclin analogs with biological significance
-
A three-component coupling procedure was developed to construct the entire prostaglandin (PG) skeleton under HMPA-free and stoichiometric conditions via a combination of dimethylzinc-aided conjugate addition of an ω-side-chain vinyllithium with (R)-4-hydroxy-2-cyclopentenone and the direct trapping of the resulting enolate with an α-side-chain propargyl triflate. Dimethylzinc effectively regulated both the conjugate addition and alkynylation reactions. Thus, the method afforded protected 5,6-didehydro-PGE2, a common intermediate for the general synthesis of natural PGs and the stable artificial prostacyclin (PGI2) analog isocarbacyclin in 88% yield. The utility of the method was further applied to the syntheses of novel intermediates, which are useful for the straightforward synthesis of 15R-TIC and 15-deoxy-TIC in 79% and 86% yield, respectively.
- Koyama, Hiroko,Izumiseki, Atsuto,Suzuki, Masaaki
-
p. 1467 - 1470
(2019/05/07)
-
- Synthesis, conformational preferences, and biological activity of conformational analogues of the microtubule-stabilizing agents, (-)-zampanolide and (-)-dactylolide
-
Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding of the conformational preferences of the macrolide core in both natural products, we hypothe
- Henry, Jeffrey L.,Wilson, Matthew R.,Mulligan, Michael P.,Quinn, Taylor R.,Sackett, Dan L.,Taylor, Richard E.
-
supporting information
p. 800 - 805
(2019/05/29)
-
- 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)
-
- Two simple and alternative approaches for the synthesis of anticancer active goniothalamin
-
Two alternative and straightforward routes were developed for the construction of (R)-goniothalamin, a natural anticancer agent. The first method starts with (R)-glycidol involving stereoselective (partial) reduction of alkyne and sulfoxide Julia-Lythgoe
- Narasimhulu, Manchala,Siva Prasad,Appa, Rama Moorthy,Lakshmidevi, Jangam,Venkateswarlu, Katta
-
p. 326 - 337
(2018/07/05)
-
- Total Synthesis of Belizentrin Methyl Ester: Report on a Likely Conquest
-
The assigned structure of the dinoflagellate-derived toxin belizentrin was prepared by total synthesis in form of the corresponding methyl ester for stability reasons. The successful route features an unusual solution for the preparation of a recalcitrant ylide on a C-glycosidic segment; moreover, it involves an asymmetric hetero-Diels–Alder reaction en route to the tertiary hemiacetal substructure, a Negishi cross-coupling of two elaborate building blocks, and a macrocyclization based on an intramolecular aminolysis of a spirolactone. A modified Kocienski olefination ultimately allowed the polyol side chain to be attached to the macrocycle although this transformation faced the exceptional base sensitivity of this polyunsaturated target compound.
- Anderl, Felix,Gr??l, Sylvester,Wirtz, Conny,Fürstner, Alois
-
supporting information
p. 10712 - 10717
(2018/08/17)
-
- Total Synthesis and Biological Activity of the Arachidonic Acid Metabolite Hemiketal E2
-
The total synthesis of hemiketal E2 (HKE2) has been accomplished using a gold(I)-mediated cycloisomerization followed by oxidation of the enol ether product to introduce a unique keto-hemiketal, the core structure of HKE2.
- Boer, Robert E.,Giménez-Bastida, Juan Antonio,Boutaud, Olivier,Jana, Somnath,Schneider, Claus,Sulikowski, Gary A.
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p. 4020 - 4022
(2018/07/15)
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- Total Synthesis of GKK1032A2 via Direct 13-Membered Macrocyclization Using a Nucleophilic Aromatic Substitution of an (η6-Arene)Chromium Complex
-
The first enantioselective total synthesis of GKK1032A2 has been achieved. The key step is a direct construction of the highly strained 13-membered macrocycle of GKK1032A2 by an intramolecular nucleophilic aromatic substitution (SNAr) reaction. This is the first successful example of construction of a macrocycle with an aryl ether linkage utilizing an intramolecular SNAr reaction of an (η6-arene)chromium complex.
- Sugata, Hayato,Inagaki, Kensuke,Ode, Toshiaki,Hayakawa, Tomoki,Karoji, Yuki,Baba, Motoaki,Kato, Ryo,Hasegawa, Daiju,Tsubogo, Tetsu,Uchiro, Hiromi
-
p. 628 - 632
(2017/03/22)
-
- Callipeltosides A, B and C: Total Syntheses and Structural Confirmation
-
Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1-C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10-C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2). Easy as A, B, C: The entire callipeltoside family of natural products have been synthesised in a highly convergent manner. This account details our full research effort and presents further evidence to aid in the stereochemical assignment of the glycosidic linkages present in callipeltosides B and C (see scheme).
- Frost, James R.,Pearson, Colin M.,Snaddon, Thomas N.,Booth, Richard A.,Turner, Richard M.,Gold, Johan,Shaw, David M.,Gaunt, Matthew J.,Ley, Steven V.
-
supporting information
p. 13261 - 13277
(2015/09/15)
-
- Inhibition of quorum sensing and biofilm formation in Vibrio harveyi by 4-fluoro-DPD; A novel potent inhibitor of AI-2 signalling
-
(S)-4,5-Dihydroxypentane-2,3-dione [(S)-DPD, (1)] is a precursor for AI-2, a quorum sensing signalling molecule for inter- and intra-species bacterial communication. The synthesis of its fluoro-analogue, 4-fluoro-5-hydroxypentane- 2,3-dione (2) is reported. An intermediate in this route also enables a new, shorter synthesis of the native (S)-DPD. 4-Fluoro-DPD (2) completely inhibited bioluminescence and bacterial growth of Vibrio harveyi BB170 strain at 12.5 μM and 100 μM, respectively.
- Kadirvel, Manikandan,Fanimarvasti, Fariba,Forbes, Sarah,McBain, Andrew,Gardiner, John M.,Brown, Gavin D.,Freeman, Sally
-
supporting information
p. 5000 - 5002
(2014/05/06)
-
- Stereoselective synthesis of C19-C27 fragment of bryostatin 11
-
A convergent synthesis of C19-C27 fragment (2) of bryostatin-11 is described. The key steps involved in this approach are kinetic resolution, Grignard reaction, and Sharpless dihydroxylation. AIBN catalyzed radical cyclization strategy has been used for the first time to construct the six-membered pyran system.
- Yadav,Swamy,Subba Reddy,Ravinder
-
p. 4054 - 4056
(2014/07/22)
-
- Stereoselective synthesis of C19-C27 fragment of bryostatin 11
-
A convergent synthesis of C19-C27 fragment (2) of bryostatin-11 is described. The key steps involved in this approach are kinetic resolution, Grignard reaction, and Sharpless dihydroxylation. AIBN catalyzed radical cyclization strategy has been used for the first time to construct the six-membered pyran system.
- Yadav,Swamy,Subba Reddy,Ravinder
-
p. 4054 - 4056
(2015/02/02)
-
- A reductive coupling strategy towards ripostatin A
-
Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9-C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1-C9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10-C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted decarboxylation enables construction of the C15-C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment.
- Schleicher, Kristin D.,Jamison, Timothy F.
-
supporting information
p. 1533 - 1550
(2013/10/22)
-
- Total synthesis of (-)-zampanolide and structure-activity relationship studies on (-)-dactylolide derivatives
-
A new total synthesis of the marine macrolide (-)-zampanolide (1) and the structurally and stereochemically related non-natural levorotatory enantiomer of (+)-dactylolide (2), that is, ent-2, has been developed. The synthesis features a high-yielding, selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction to close the 20-membered macrolactone ring of 1 and ent-2. The β-keto phosphonate/aldehyde precursor for the ring-closure reaction was obtained by esterification of a ω-diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent-2. THP ring formation was accomplished through a segment coupling Prins-type cyclization. Employing the same overall strategy, 13-desmethylene-ent-2 as well as the monocyclic desTHP derivatives of 1 and ent-2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro with nM IC50 values, while ent-2, which lacks the diene-containing hemiaminal-linked side chain of 1, is 25- to 260-fold less active. 13-Desmethylene-ent-2 as well as the reduced versions of ent-2 and 13-desmethylene-ent-2 all showed similar cellular activity as ent-2 itself. The same activity level was attained by the monocyclic desTHP derivative of 1. Oxidation of the aldehyde functionality of ent-2 gave a carboxylic acid that was converted into the corresponding N-hexyl amide. The latter showed only μM antiproliferative activity, thus being several hundred-fold less potent than 1. It's the side chain that matters: The marine macrolide (-)-zampanolide (1) has been synthesized via (-)-dactylolide (ent-2), the non-natural enantiomer of the marine natural product (+)-dactylolide (2), employing a high-yielding intramolecular Horner-Wadsworth-Emmons reaction to close the macrolactone ring. While the hemiaminal-linked side chain in 1 is crucial for nanomolar antiproliferative activity, the methylene group and the aldehyde functionality in ent-2 are dispensable. A monocyclic destetrahydropyran derivative of 1 shows equal activity as ent-2. Copyright
- Zurwerra, Didier,Glaus, Florian,Betschart, Leo,Schuster, Julia,Gertsch, Jürg,Ganci, Walter,Altmann, Karl-Heinz
-
supporting information
p. 16868 - 16883
(2013/03/14)
-
- Total synthesis of (+)-anamarine
-
Total synthesis of (+)-anamarine a polyoxygenated δ-pyranone natural product was accomplished via cross-metathesis protocol starting from 3-butene-1-ol and glycidol. Other key features of this synthetic strategy include use of Sharpless asymmetric epoxida
- Kumar, Krishnammagari Suresh,Reddy, Cirandur Suresh
-
p. 2647 - 2655
(2012/04/23)
-
- Total synthesis of (-)-goniotrionin
-
A stereoselective total synthesis of the reported structure of goniotrionin (4) has been accomplished. The key steps involved the opening of a chiral epoxide, a highly diastereoselective Mukaiyama aerobic oxidative cyclization, a selective 1,2-syn Mukaiyama aldol reaction, and a Noyori reduction.
- Dias, Luiz C.,Ferreira, Marco A. B.
-
scheme or table
p. 4046 - 4062
(2012/06/29)
-
- A flexible organocatalytic enantioselective synthesis of heptadeca-1-ene-4,6-diyne-3S,8R,9S,10S-tetrol and its congeners
-
A unified enantioselective route is developed for the synthesis of heptadeca-1-ene-4,6-diyne-3S,8R,9S,10S-tetrol and its synthetic congeners. A proline-catalyzed aminoxylation, cross-metathesis, Wittig reaction, and catalytic dihydroxylation are key steps
- Kumaraswamy, Gullapalli,Sadaiah, Kadivendi
-
p. 262 - 271
(2012/01/14)
-
- Synthesis of (-)-dactylolide and 13-desmethylene-(-)-dactylolide and their effects on tubulin
-
An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (-)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the sub-micromolar range and induce the polymerization of tubulin in vitro.
- Zurwerra, Didier,Gertsch, Juerg,Altmann, Karl-Heinz
-
supporting information; experimental part
p. 2302 - 2305
(2010/08/05)
-
- Enantioselective synthesis of structurally intricate and complementary polyoxygenated building blocks of spongistatin 1 (altohyrtin a)
-
Enantioselective approaches to the construction of four complex building blocks of the structurally intricate marine macrolide known as spongistatin 1 are presented. The first phase of the synthetic effort relies on a practical approach to a desymmetrized, enantiomerically pure spiroketal ring system incorporating rings A and B. Concurrently, the C17-C28 subunit, which houses one-fifth of the stereogenic centers of the target in the form of rings C and D, was assembled via a composite of stereocontrolled aldol condensations. Once arrival at the entire C1-C28 sector had been realized, routes were devised to provide two additional highly functionalized sectors consisting of C29-C44 and C38-C51. A series of subsequent transformations including cyclization of the E ring and hydroboration to afford the B-alkyl intermediate for the key Suzuki coupling to append the side chain took advantage of efficient stereocontrol. Ultimately, complete assembly and functionalization of the western EF sector of spongistatin was thwarted by an inoperative Suzuki coupling step intended to join the side chain to the C29-C44 sector, and later because of complications due to protecting groups, which precluded the complete elaboration of the late stage C29-C51 intermediate.
- Braun, Alain,Cho, Ii Hwan,Ciblat, Stephane,Clyne, Dean,Forgione, Pat,Hart, Amy C.,Huang, Guoxiang,Kim, Jungchul,Modolo, Isabelle,Paquette, Leo A.,Peng, Xiaowen,Pichlmair, Stefan,Stewart, Catherine A.,Wang, Jizhou,Zuev, Dmitry
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experimental part
p. 651 - 769
(2010/02/27)
-
- Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2
-
Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a CaII ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of CaII ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.
- Smith III, Amos B.,Lin, Qiyan,Doughty, Victoria A.,Zhuang, Linghang,McBriar, Mark D.,Kerns, Jeffrey K.,Boldi, Armen M.,Murase, Noriaki,Moser, William H.,Brook, Christopher S.,Bennett, Clay S.,Nakayama, Kiyoshi,Sobukawa, Masao,Lee Trout, Robert E.
-
supporting information; experimental part
p. 6470 - 6488
(2011/02/25)
-
- Total synthesis of (-)-zampanolide and questionable existence of (-)-dactylolide as the elusive biosynthetic precursor of (-)-zampanolide in an okinawan sponge
-
A new and concise total synthesis of (-)-zampanolide, (-)-1, and (-)-dactylolide, (-)-2, is described. Synthetic highlights include (i) a mild Horner-Wadsworth-Emmons reaction providing the seco acid, (II) an unusual stepwise cross-coupling reaction of a
- Uenishi, Jun'ichi,Iwamoto, Takuya,Tanaka, Junichi
-
scheme or table
p. 3262 - 3265
(2009/12/25)
-
- Versatile synthesis of the C3-C14 domain of 7-deoxyokadaic acid
-
Described is a flexible synthesis of the C3-C14 domain of 7-deoxyokadaic acid that is amenable to facile structural diversification. Treatment of ynone 10 under acidic conditions led to net bis-conjugate addition of the latent diol to give the thermodynam
- Trygstad, Timothy M.,Pang, Yucheng,Forsyth, Craig J.
-
supporting information; experimental part
p. 910 - 913
(2009/06/20)
-
- Hemicryptophane-oxidovanadium(V) complexes: Lead of a new class of efficient supramolecular catalysts
-
Hemicryptophane-oxidovanadium(V) complexes 1 and 2 were tested in the oxidation of sulfide to sulfoxide. They were found to be efficient supramolecular catalysts in the oxidation of thioanisol with yields up to 95%. Furthermore, turnover up to 180 was obt
- Martinez, Alexandre,Dutasta, Jean-Pierre
-
experimental part
p. 188 - 192
(2009/12/26)
-
- A stereoselective approach for the total synthesis of clonostachydiol
-
A stereoselective synthesis of clonostachydiol is accomplished using readily available (±)-epichlorohydrin as a precursor. The synthesis involves direct and straightforward reactions such as Sharpless asymmetric epoxidation, iodination, stereoselective op
- Yadav,Swamy,Subba Reddy
-
body text
p. 2773 - 2776
(2009/04/16)
-
- Total synthesis of solandelactones A, B, E, and F exploiting a tandem petasis-claisen lactonization strategy
-
(Chemical Equation Presented) Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (75) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C22 oxylipins that parallels a hypothesis put forward previously to explain the origin of C20 cyclopropane-containing algal products.
- White, James D.,Lincoln, Christopher M.,Yang, Jongtae,Martin, William H. C.,Chan, David B.
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p. 4139 - 4150
(2008/09/20)
-
- Total synthesis of (R)-(+)-goniothalamin and (R)-(+)-goniothalamin oxide: first application of the sulfoxide-modified Julia olefination in total synthesis
-
A short and efficient synthesis of (R)-(+)-goniothalamin 1 and (R)-(+)-goniothalamin oxide 2 is described. During this approach, the sulfoxide-modified Julia olefination was used as a key step to connect aldehyde 5 to sulfoxide 6. The desired styryl-containing adduct is obtained in good yield and with excellent E/Z selectivity.
- Pospí?il, Ji?í,Markó, István E.
-
p. 5933 - 5937
(2007/10/03)
-
- Stereochemistry of hydrogen removal from the 'unactivated' C-3 position of 4-hydroxybutyryl-CoA catalysed by 4-hydroxybutyryl-CoA dehydratase.
-
(R)- and (S)-gamma-[3-(2)H(1)]butyrolactones have been synthesised from (R)- and (S)-glycidol, respectively, and used to demonstrate that it is the pro-(S) hydrogen atom that is stereospecifically abstracted from C-3 of 4-hydroxybutyryl-CoA by 4-hydroxybu
- Scott, Richard,Naeser, Ulrike,Friedrich, Peter,Selmer, Thorsten,Buckel, Wolfgang,Golding, Bernard T
-
p. 1210 - 1211
(2007/10/03)
-
- Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of sharpless' asymmetric epoxidation
-
Three different routes are described for the synthesis of deoxylaulimalide (3), which is the immediate precursor of the marine sponge metabolite laulimalide (1). These routes mainly differ with respect to their ring closing step. Thus, route 1 uses a Still-Gennari olefination, route 2 a Yamaguchi lactonization, and route 3 an intramolecular allylsilane-aldehyde addition for establishing the macrocyclic structure. The unprotected deoxy derivative 3 was subjected to Sharpless' asymmetric epoxidation (SAE). With (R,R)-tartrate the 16,17-epoxide laulimalide (1) is formed selectively, whereas (S,S)-tartrate generates the 21,22-epoxide 142. This demonstrates the high reagent control involved in the SAE process, which in this case is used to achieve high stereo- and regioselectivity. Laulimalide and some derivatives thereof have been tested with respect to antitumor activity and compared to standard compounds paclitaxel and epothilone B.
- Ahmed, Anjum,Hoegenauer, E. Kate,Enev, Valentin S.,Hanbauer, Martin,Kaehlig, Hanspeter,Ohler, Elisabeth,Mulzer, Johann
-
p. 3026 - 3042
(2007/10/03)
-
- Total Synthesis of Apoptolidin: Construction of Enantiomerically Pure Fragments
-
A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthes
- Nicolaou,Fylaktakidou, Konstantina C.,Monenschein, Holger,Li, Yiwei,Weyershausen, Bernd,Mitchell, Helen J.,Wei, Heng-Xu,Guntupalli, Prasuna,Hepworth, David,Sugita, Kazuyuki
-
p. 15433 - 15442
(2007/10/03)
-
- A Practical and Efficient Synthesis of the C-16-C-28 Spiroketal Fragment (CD) of the Spongistatins
-
(Equation Presented) A practical and efficient route to the CD spiroketal (C-16-C-28) of the spongistatins is reported. Two stereocenters are introduced from chiral building blocks with the remainder introduced by substrate-controlled transformations. The
- Gaunt, Matthew J.,Hook, David F.,Tanner, Huw R.,Ley, Steven V.
-
p. 4815 - 4818
(2007/10/03)
-
- Total synthesis of apoptolidin: Part 1. Retrosynthetic analysis and construction of building blocks
-
No less than 30 stereogenic elements, a highly unsaturated 20-membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin (1) a challenging synthetic target. The retrosynthetic analysis reve
- Nicolaou,Li, Yiwei,Fylaktakidou, Konstantina C.,Mitchell, Helen J.,Wei, Heng-Xu,Weyershausen, Bernd
-
p. 3849 - 3854
(2007/10/03)
-
- Synthesis of the macrocyclic core of apoptolidin
-
The convergent synthesis of the apoptolidin macrocyclic core is described.
- Nicolaou,Li, Yiwei,Weyershausen, Bernd,Wei, Heng-Xu
-
p. 307 - 308
(2007/10/03)
-
- Synthesis of the C15-C27 fragment of the antitumor agent laulimalide
-
A stereocontrolled synthesis of the C15-C27 fragment of laulimalide is described. Key features are a divergent-convergent synthesis from (R)-glycidol, an interesting formation of a trisubstituted double bond via ring closing metathesis with Grubbs' ruthen
- Dorling,Ohler,Mulzer
-
p. 6323 - 6326
(2007/10/03)
-
- Synthesis and in vitro cancer cell growth inhibitory activity of monocyclic model compounds containing spongistatin triene side-chains
-
Two monosaccharides embodying triene side-chains of the spongistatins display significant in vitro activity against human cancer cell lines.
- Smith III, Amos B.,Lin, Qiyan,Pettit, George R.,Chapuis, Jean-Charles,Schmidt, Jean M.
-
p. 567 - 568
(2007/10/03)
-
- Spongistatin synthetic studies. 1. Construction of a C(29-48) subtarget
-
In this Letter, the first in a series of three, we outline our overall strategy and describe the assembly of a C(29-48) EF-ring advanced intermediate for the total synthesis of the spongistatins, rare and structurally unique polyether macrolides with unpr
- Smith III, Amos B.,Zhuang, Linghang,Brook, Christopher S.,Boldi, Armen M.,McBriar, Mark D.,Moser, William H.,Murase, Noriaki,Nakayama, Kiyoshi,Verhoest, Patrick R.,Lin, Qiyan
-
p. 8667 - 8670
(2007/10/03)
-
- A Convenient Synthesis of Platelet-Activating Factors and Their Analogues from Chiral Epichlorohydrin
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Two platelet activating factors (PAF) were conveniently prepared from optically active epichlorohydrin via 5 steps in 15-16percent total yield.Four analogues containing oleoyl, propyl, p-trifluoromethylphenoxy, and N,N-dimethyldithiocarbamoyl groups were also prepared.
- Tsuboi, Sadao,Takeda, Shinji,Yamasaki, Yasuhisa,Sakai, Takashi,Utaka, Masanori,et al.
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p. 1417 - 1420
(2007/10/02)
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