- Glycosyl-nucleolipids as new bioinspired amphiphiles
-
Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lowerγlim) compared to the first generation of GNFs.
- Latxague, Laurent,Patwa, Amit,Amigues, Eric,Barthelemy, Philippe
-
-
Read Online
- Toward an Asymmetric Synthesis of Bistramide K
-
The bistramides family has shown antitumoral activity. More specifically bistramide K exhibits lower toxicity than its congeners. In this work, we describe a highly stereoselective and convergent synthesis of two building blocks of the marine metabolite b
- Bauder, Claude
-
p. 4874 - 4899
(2018/09/10)
-
- The total synthesis of calcium atorvastatin
-
A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.
- Dias, Luiz C.,Vieira, Adriano S.,Barreiro, Eliezer J.
-
supporting information
p. 2291 - 2296
(2016/03/01)
-
- Studies directed towards the total synthesis of koshikalide: Stereoselective synthesis of the macrocyclic core
-
The stereoselective synthesis of the macrolactone core of the natural product koshikalide is described. Starting with readily available 1,4-butanediol and malic acid as synthons, our synthetic strategy involved the reiterative application of Gilman's reaction, Swern oxidation and Sharpless asymmetric epoxidation to establish the required stereocentres. Other key steps in the synthesis include Negishi cross coupling and Horner-Wadsworth-Emmons (HWE) reactions for construction of the main fragments. The 14-membered lactone ring was prepared by a selective Mitsunobu macrolactonization approach.
- Venkanna, Arramshetti,Sreedhar, Eppakayala,Siva, Bandi,Babu, Katragadda Suresh,Prasad, Kothakonda Rajendra,Rao, Janaswamy Madhusudana
-
p. 1010 - 1022
(2013/09/23)
-
- 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)
-
- Stereoselective synthesis of tetrahydropyranyl diarylheptanoids (-)-centrolobine and (+)-centrolobine
-
A versatile chiron approach to the tetrahydropyranyl diarylheptanoid natural products (-)-centrolobine and (+)-centrolobine has been described. The use of an aldol reaction followed by reductive etherification for the formation of tetrahydropyran ring is of importance. Georg Thieme Verlag Stuttgart · New York.
- Reddy, Chada Raji,Madhavi, Pasupulety Phani,Chandrasekhar, Srivari
-
scheme or table
p. 123 - 126
(2011/02/26)
-
- Application of stereoselective ether transfer to the synthesis of isotactic polyethers
-
An efficient, convergent synthetic strategy has been developed which enables the synthesis of a series of naturally occurring isotactic polymethoxy compounds. Ether transfer followed by a hydride workup enables simultaneous, diastereoselective production of two methoxy centers in a single step. High yields and diastereoselectivity are observed even in stereochemically rich, polyoxygenated systems. Direct generation of bis-methyl ether moieties from methoxymethyl ethers minimizes the need for typical protective group strategies and the use of expensive methyl transfer reagents. Moreover, the simultaneous generation of a terminal primary iodide serves as a coupling partner for the generation of higher order congeners.
- Liu, Kai,Arico, Joseph W.,Taylor, Richard E.
-
scheme or table
p. 3953 - 3957
(2010/08/07)
-
- Highly stereoselective hydrogenations-as key-steps in the total synthesis of statins
-
Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) and became the standard of care for treatment of hypercholesterolemia because of their efficacy, safety, and long-term benefits. They are administered as diaste
- Andrushko, Natalia,Andrushko, Vasyl,Tararov, Vitali,Korostylev, Andrei,Koenig, Gerd,Boerner, Armin
-
scheme or table
p. 534 - 541
(2010/08/20)
-
- Structure elucidation and stereoselective total synthesis of pavettamine, the causal agent of gousiekte
-
The structure elucidation of a novel natural product pavettamine (1), the causal agent of the plant toxicosis gousiekte, is reported. The structure was defined by analysis of NMR and MS data and the relative configuration followed from the 13C NMR data of the acetonide derivative. The absolute stereochemistry was established by total synthesis from (2S)-malic acid using chiral sulfoxide methodology as (2S,4R,8R,10S)-1,11-diamino-6-aza-undecane-2,4,8,10-tetraol.
- Bode, Moira L.,Gates, Paul J.,Gebretnsae, Samson Y.,Vleggaar, Robert
-
supporting information; experimental part
p. 2026 - 2036
(2010/04/26)
-
- Synthesis and highly stereoselective hydrogenation of the statin precursor ethyl (5S)-5,6-isopropylidenedioxy-3-oxohexanoate
-
A search for the large-scale preparation of (5S)-5,6-(isopropylidenedioxy)- 3-oxohexanoates (2) - a key intermediate in the synthesis of pharmacologially important statins - starting from (S)-malic acid is described. The synthesis of the required initial compound methyl (3S)-3,4-(isopropylidenedioxy)butanoate (1) by Moriwake's reduction of dimethyl (S)-malate (3) has been improved. Direct 2-C chain elongation of ester 1 using the lithium enolate of tert-butyl acetate has been shown to be successful at a 3- to 5-fold excess of the enolate. Unfortunately, the product, tert-butyl (5S)-5,6-(isopropylidenedioxy)-3- oxohexanoate (2a) is unstable during distillation. Ethyl (5S)-5,6- (isopropylidenedioxy)-3-oxohexanoate (2b) was prepared alternatively on a multigram scale from (3S)-3,4-(isopropylidenedioxy)butanoic acid (7) by activation with N,N′-carbonyldiimidazole and subsequent reaction with Mg(OOCCH2COOEt)2. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester (2b) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β-keto ester (2b) to ethyl (55)-5,6-(isopropylidenedioxy)- 3-hydrohyhexanoate (syn-6 and anti-6) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)- and (R)-BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn-6/anti-6 = 2.3 was observed with an achiral (Ph3P)3RuCl2 catalyst. Ru[(R)-Tol-BINAP]Cl2 neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn-(5S)-5,6-isopropylidenedioxy-3-hydroxyhexanoate (syn-6) at a preparative substrate/catalyst ratio of 1000:1.
- Tararov, Vitali I.,Koenig, Gerd,Boerner, Armin
-
p. 2633 - 2644
(2007/10/03)
-
- METHOD FOR THE PRODUCTION OF STATINS
-
The invention relates to a method for producing statins known as HMG-CoA reductase inhibitors. Some of the intermediate compounds used in the inventive method are novel compounds. The invention also relates to said novel intermediate compounds.
- -
-
Page/Page column 24-25
(2010/11/24)
-
- METHOD FOR THE PRODUCTION OF STATINS
-
The invention relates to a method for the production of a statin. Said method comprises the following steps: a) a compound of formula (II) is produced, wherein S1 represents a hydrogen atom or a hydroxyl protective group, S2 and S3 independently represent a hydroxyl protective group and R1 represents a hydrogen atom or a carboxyl protective group. Said compound of formula (II) is produced by stereoselective hydrogenation of a compound of formula (III) in order to form a compound of formula (II-a) and, optionally, by introducing a hydroxyl protective group. b) by lactonising the compound of formula II in order to form a compound of formula (I-a).
- -
-
Page/Page column 25
(2010/02/11)
-
- Synthesis of the C-1-C-28 ABCD Unit of Spongistatin 1
-
(Equation Presented) The synthesis of the C-1-C-28 ABCD fragment of spongistatin is described. Anti-selective boron-mediated aldol coupling of a CD spiroketal ketone fragment to an AB spiroketal aldehyde unit forms the desired C1-C28 advanced intermediate
- Gaunt, Matthew J.,Jessiman, Alan S.,Orsini, Paolo,Tanner, Huw R.,Hook, David F.,Ley, Steven V.
-
p. 4819 - 4822
(2007/10/03)
-
- Synthesis and applications of C2-symmetric guanidine bases
-
The preparation of tetracyclic C2-symmetric guanidinium salts is reported together with their application to enantioselective transformations.
- Allingham, Matthew T.,Howard-Jones, Andrew,Murphy, Patrick J.,Thomas, Dafydd A.,Caulkett, Peter W. R.
-
p. 8677 - 8680
(2007/10/03)
-
- Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase.
-
The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.
- Dardonville, Christophe,Gilbert, Ian H
-
p. 552 - 559
(2007/10/03)
-
- Stereoselective tetrahydropyrido[2,1-a]isoindolone synthesis via carbanionic and radical intermediates: A model study for the Tacaman alkaloid D/E ring fusion
-
Stereoselective cyclisation of malic acid-derived α-sulfanyllactam (1) via radical and carbanionic intermediates affords stereo-defined tetrahydropyrido[2,1-a]isoindolones as model compounds for the D/E cis-ring fusion of the Tacaman indole alkaloid skele
- Hunter, Roger,Richards, Philip
-
p. 3755 - 3758
(2007/10/03)
-
- Approaches to the C-24 to C-37 perimeter of Altohyrtin A
-
Versatile synthetic sequences are described for the C-24 to C-37 perimeter of Altohyrtin A 1. In addition the diastereoselectivity for the reduction of the β-alkoxy ynone system 15 using various hydride reagents is described.
- Hermitage, Stephen A.,Roberts, Stanley M.,Watson, Daniel J.
-
p. 3567 - 3570
(2007/10/03)
-
- Total synthesis of milbemycin E: Synthesis of the C(11)-C(25) fragment
-
Treatment of 2-methylpropanal with the (E)-but-2-enyl(diisopinocampheyl)borane 9 prepared from (+)-α-pinene gives the anti- and syn-products 10 and 11, ratio 88:12, from which the major anti-isomer 10 is separated by preparative GLC. Hydroboration-oxidation of its tert-butyldimethylsilyl ether 14 gives the primary alcohol 15 which has been converted into the bromide 16 and iodide 17. The propenyl(diisopinocampheyl)borane 23 prepared from (-)-α-pinene reacts with the aldehyde 22 prepared from (S)-malic acid to give the anti- and syn-1,3-diol derivatives 24 and 25, ratio 86:14, and the anti-product 24 has been taken through to the epoxide 31. Sequential alkylation of 1,3-dithiane with the iodide 17 and the epoxide 31 gives the 2,2-dialkyl-1,3-dithiane 33 which is converted into the spiroacetal 4 by treatment with dilute aqueous hydrogen fluoride. After protection, ozonolysis gives the aldehyde 43 which has been condensed with the ylide 34 to give the α,β-unsaturated ester 44. This has been reduced and converted into the iodide 46 which has been used to alkylate the chiral oxazolidinone 39 to give the required C(11)-C(25) fragment 48 of milbemycin E 1 after reductive removal of the chiral auxiliary. This has been converted into the phosphonium salt 2 ready for Wittig coupling with the hydroxybutenolide 3 for the assembly of the milbemycin nucleus.
- Steel, Patrick G.,Thomas, Eric J.
-
p. 371 - 380
(2007/10/03)
-
- Synthetic studies towards pateamine, a novel thiazole-based 19-membered bis-lactone from Mycale sp
-
A concise synthesis of the 19-membered bis-lactone core 2b present in pateamine 1 using chiral pool starling materials and featuring an intramolecular Stille coupling reaction as a key stratagem, is described. Copyright (C) 1996 Elsevier Science Ltd.
- Critcher, Douglas J.,Pattenden, Gerald
-
p. 9107 - 9110
(2007/10/03)
-
- A revised mechanism for chemoselective reduction of esters with borane-dimethyl sulfide complex and catalytic sodium tetrahydroborate directed by adjacent hydroxyl group
-
The plausible mechanism for the reduction of the ester groups with a strong preference for one located α to the hydroxyl groups of (S)-malates and (R,R)-tartrate-based derivatives has been proposed together with some results with regard to its applications to the syntheses of chiral synthons.
- Saito,Ishikawa,Kuroda,Koga,Moriwake
-
p. 4067 - 4086
(2007/10/02)
-
- SYNTHESES OF 1-OXAQUINOLIZIDINES VIA REDUCTIVE CYCLIZATION OF HYDROXY-LACTAMS
-
The synthesis of the 1-oxaquinolizidine moiety of xestospongin A via reductive iminium ion formation from a lactam is described. Key Words: 1-oxaquinolizidine; iminium ion; "ate" complex from DIBAL and n-BuLi; xestospongin A; iminium ion-enamine tautomeri
- Ahn, Kyo Han,Lee, Seok Jong
-
p. 507 - 510
(2007/10/02)
-
- Electroreductive Deoxygenation of Methanesulfonates of α-Hydroxy Esters via a Catalytic Selenation-Deselenation Sequence
-
The methanesulfonates of α-hydroxy esters were converted to the corresponding deoxygenated esters in 70-88percent yields by the indirect electrolysis with diphenyl diselenide as a recyclable reagent in a divided cell.This deoxygenation method may involve the formation of α-phenylselenoester by replacement of α-methylsulfonyloxy group with phenylselenide anion followed by capture of the α-phenylseleno group with phenylselenide anion.
- Inokuchi, Tsutomu,Sugimoto, Tatsuya,Kusumoto, Masahiko,Torii, Sigeru
-
p. 3200 - 3202
(2007/10/02)
-
- Synthesis of the Oviposition-Deterring Pheromone of Rhagoletis cerasi L.
-
The oviposition-deterring pheromone of Rhagoletis cerasi L. (-)-(8R,15R)-1 and a mixture of the two compounds (-)-(8R and 8S,15R)-1 have been synthesized.In the presence of the 1,5-cyclooctadiene-CuCl complex as a catalyst the Grignard reagent of (-)-(R)-
- Kuechler, Birgit,Voss, Gundula,Gerlach, Hans
-
p. 545 - 552
(2007/10/02)
-
- A new practical enantiospecific synthesis of unlabelled and tritium labelled 12-HETEs
-
The oxidative metabolism of arachidonic acid AA is known to yield a variety of biologically active substances.Among them, both enantiomers of 12-hydroxyeicosatetraenoic acid (12-HETE) have been the subject of much interest.In order to extend their biologi
- Mosset, P.,Pointeau, P.,Aubert, F.,Lellouche, J. P.,Beaucourt, J. P.,Gree, R.
-
p. 298 - 315
(2007/10/02)
-
- Convenient One-Pot Conversion of Alcohols into Esters via Hemiacetal Intermediates
-
A simple and efficient one-pot oxidative procedure, adaptable to a large scale, is described for the preparation of methyl esters from either primary alcohols or vic-diols.The aldehyde is generated by Swern or periodate oxidation, followed by bromine oxidation of the methyl hemiacetal formed in aqueous methanolic solution.
- Lichtenthaler, Frieder W.,Jarglis, Pan,Lorenz, Klaus
-
p. 790 - 792
(2007/10/02)
-
- Use of Enzymatic Hydrolysis of Dimethyl Malates for a Short Synthesis of Tulipalin B and of Its Enantiomer
-
Pig liver esterase (PLE) hydrolyzes the ester function α to the hydroxyl group in dimethyl malate.This regiospecific reaction was used to synthesize (+)- and (-)-tulipalin B.
- Papageorgiou, Christos,Benezra, Claude
-
p. 1144 - 1145
(2007/10/02)
-
- COMBINATION OF BORANE-DIMETHYL SULFIDE COMPLEX WITH CATALYTIC SODIUM TETRAHYDROBORATE AS A SELECTIVE REDUCING AGENT FOR α-HYDROXY ESTERS, VERSATILE CHIRAL BUILDING BLOCK FROM (S)-(-)-MALIC ACID
-
Borane-dimethyl sulfide complex has proven to be an efficient and selective reducing agent in the presence of sodium tetrahydroborate for α-hydroxy esters as exemplified in the reduction of dimethyl (S)-(-)-malate, providing the versatile chiral building block of four-carbon backbone.
- Saito, Seiki,Hasegawa, Takashi,Inaba, Masami,Nishida, Ryosuke,Fujii, Toshikazu,et. al
-
p. 1389 - 1392
(2007/10/02)
-