- Total Synthesis of the Echinodermatous Ganglioside LLG-3 Possessing the Biological Function of Promoting the Neurite Outgrowth
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A total synthesis of echinodermatous ganglioside LLG-3 with neuritogenic activity was accomplished by a convergent strategy. The synthesis of 2-hydroxyethyl 8-O-Me-α-sialoside 2 was started from the phenyl 7,8-di-O-Pico-thiosialoside 5, which can be chemoselectively removed the picoloyl group, and then the methyl group in 8-O-MeNeu5Ac moiety was chemoselectively prepared using TMSCHN2/FeCl3. For preparation of the terminal disialic unit, oxidative amidation was initially utilized by our group to efficiently construct the α(2,11) linkage of 8-O-Me-Neu5Acα(2,11)Neu5Gc. Herein, we also demonstrate that the synthesized ganglioside LLG-3 exhibited the neuritogenic activity toward the primary cortical neurons and that biological activity is superior to that of ganglioside DSG-A.
- Huang, Yuahn-Sieh,Shih, Jing-Feng,Tsai, Yow-Fu,Wu, Yu-Fa
-
supporting information
p. 7491 - 7495
(2020/10/09)
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- Stereoselective Synthesis of C1–C7 and C6–C22 Fragments of Phostriecin, Goniothalamines, and Their Analogues
-
The stereoselective synthesis of two fragments (C1–C7 and C6–C22) of the anti-tumor agent phostriecin has been achieved. The chiral hydroxy-vinyl-δ-lactone building block (fragment C1–C7) was subsequently utilized for the synthesis of 5-hydroxygoniothalamin, 5-acetoxygoniothalamin, and their derivatives.
- Purushotham Reddy,Vasudeva Reddy,Sabitha, Gowravaram
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p. 4389 - 4399
(2018/09/11)
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- Stereoselective Synthesis of the C27-C35 Eribulin Fragment and Its Utilization in Building Structurally Diverse Macrocycles
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A practical and scalable stereoselective synthesis of the western substituted tetrahydrofuran ring C27-C35 fragment of eribulin was developed by using (2S,3S)-tartaric acid as a cheap starting material that was converted into an intermediate through a stereoselective vinylation and cross-metathesis as the key steps. A regio-and stero-selective intramolecular oxy-Michael cyclization or an iodocyclization reaction finally provided the required western tetrahydrofuran ring fragment and its related isomeric analogues. These key fragments were further utilized in obtaining several types of macrocyclic derivatives for exploration of their biological properties. The simplicity of our present approach has the potential to be considered for large-scale syntheses of key fragments of eribulin and related analogues.
- Konda, Saidulu,Khatravath, Mahender,Mallurwar, Naveen Kumar,Rao, Pallavi,Sripelly, Shivashankar,Iqbal, Javed,Arya, Prabhat
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p. 1663 - 1683
(2016/05/24)
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- A facile approach for the synthesis of C13-C24 fragments of maltepolides A, C and D
-
A linear, chiron approach for the synthesis of C13-C24 fragments of cytostatic maltepolides A, C and D consisting of a tetrahydrofuran subunit and a chiral alkenyl/alkyl substituent is achieved from (+)-diethyl l-tartrate. The other chiral stereocenters were generated by employing key reactions such as Crimmins aldol, alkynylation and CeCl3·7H2O mediated Luche reduction reactions.
- Rao, P. Sankara,Srihari
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p. 9629 - 9638
(2016/10/22)
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- Enantioselective Total Synthesis of the Proposed Structure of the Endophytic Fungal Metabolite Phomolide G: Structural Revision and Unambiguous Stereochemical Assignment
-
A total synthesis of the proposed structure of the natural macrolactone phomolide G (1) by a bidirectional strategy from L-tartaric acid is reported. The ω-terminus of the molecule was elaborated by nitrile extension, C3-alkylation and a substrate-controlled 1,3-ketone reduction. The α-terminus was extended by a C2aldehyde-to-alkenal homologation followed by an auxiliary controlled aldol reaction. Macrolactonization and deprotection yielded compound 1 (confirmed by X-ray analysis). This putative structure of phomolide G displayed discordant NMR spectroscopic data in comparison with those of the natural product. Detailed inspection of all NMR spectroscopic data available indicated phomolide G to be likely a diastereomer of 1. The synthetic strategy developed allows control of the absolute stereochemistry at all four chiral secondary alcohol groups. Further manipulation allowed for the preparation of diastereomer 33, the1H and13C NMR spectroscopic data of which are in full accord with that reported for the natural product.
- McNulty, James,McLeod, David,Jenkins, Hilary A.
-
supporting information
p. 688 - 692
(2017/01/18)
-
- Stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core of (+)-muconin via Prins cyclization
-
A stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core 2 of (+)-muconin (1) has been achieved using Prins cyclization as a key step to construct tetrahydropyran moiety. Other important transformations such as Wittig olefination, Sharpless epoxidation, regio-, and stereoselective exo-cyclization of the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy alcohol, Grignard reaction, and Barton-McCombie reaction are successfully employed to accomplish the synthesis of THP-THF core 2.
- Yadav,Reddy, U.V. Subba,Reddy, B.V. Subba
-
p. 3860 - 3863
(2014/07/08)
-
- Synthesis of the revised structure of acortatarin A
-
A novel Maillard-type condensation between a primary amine derived from D-mannitol and a dihydropyranone, was used as a key step to access the unusual morpholine-spiroketal acortatarin A. The synthetic approach also enabled access to a C-2 analogue of acortatarin A, and can be used for the synthesis of related 2-formylpyrrole natural products.
- Geng, Hui Min,Stubbing, Louise A.,Li-Yang Chen, Jack,Furkert, Daniel P.,Brimble, Margaret A.
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p. 6227 - 6241
(2015/03/30)
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- A facile chiral pool synthesis of 9-epi-decarestrictine-D, decarestrictine-D and O
-
A facile chiral pool total synthesis of 9-epi-decarestrictine-D, decarestrictine-D and O has been achieved from l-(+)-diethyl tartrate. The strategy utilized is conventional and flexible. Wittig homologation and Grubbs ring closing metathesis are the key reactions employed for the synthesis of the title molecules.
- Vamshikrishna, Kuchena,Srinu, Garlapati,Srihari, Pabbaraja
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p. 203 - 211
(2014/03/21)
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- Synthesis and protein kinase C (PKC)-C1 domain binding properties of diacyltetrol based anionic lipids
-
The protein kinase C (PKC) family of lipid-activated kinases plays a significant role in the regulation of diverse cellular functions including tumor promotion, apoptosis, differentiation, and others. The lipophilic second messenger diacylglycerols (DAGs) act as endogenous ligands for the PKCs in the presence of anionic phospholipids. To develop effective PKC regulators and understand the importance of anionic phospholipids in DAG binding of PKC isoforms, we conveniently synthesized octanoic acid containing diacyltetrol (DAT) based hybrid lipids with both DAG and anionic phospholipid headgroups within the same molecule. We also used palmitic and oleic acid containing hybrid lipids for additional understanding of the PKC-C1 domain binding mechanism. Biophysical studies showed that hydrophobic side chains, DAG and anionic phospholipids headgroups are necessary for their interaction with the C1-domain of PKC isoforms. The hybrid lipids DAT-PS and DAT-PA specifically interact with the PKCδ-C1b and PKCθ-C1b subdomains and showed 5- and 2.5-fold stronger binding affinity compared with DAG, respectively. Whereas, the PKCα-C1a subdomain interacts with the hybrid lipids, without any significant specificity. The present results show that hybrid lipids bind to the PKC C1b/a subdomains and can be further studied to decipher their binding mechanism and biological activities. This study proposes a new concept of developing PKC activators by using tetrol-based anionic hybrid lipids having both phospholipids and diacylglycerol headgroups within the same molecule. This study also supplies useful information for the binding potencies of hybrid lipids with PKC-C1 domains. This journal is
- Mamidi, Narsimha,Panda, Subhankar,Borah, Rituparna,Manna, Debasis
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p. 3002 - 3013
(2015/01/08)
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- Total syntheses of d-allo-1-deoxynojirimycin and l-talo-1-deoxynojirimycin via reductive cyclization
-
Synthesis of a polyhydroxypiperidine framework for l-talo-1-deoxynojirimycin and d-allo-1-deoxynojirimycin was achieved from l-tartaric acid by employing flash dihydroxylation and reductive lactamisation as the key steps. This journal is
- Chavan, Subhash P.,Dumare, Nilesh B.,Pawar, Kailash P.
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p. 40852 - 40858
(2015/02/05)
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- Stereoselective synthesis of the C13-C28 subunit of (-)-laulimalide utilizing an α-chlorosulfide intermediate
-
A stereoselective route to the C13-C28 subunit of (-)-laulimalide is described. l-Tartaric acid is the source of the hydroxy groups at C19 and C20. An α-chlorosulfide is employed as the key intermediate for the creation of the C17-C18 bond and the C16-C17 double bond was introduced using the Mislow-Braverman rearrangement and Hutchin's dexoxygenation with concomitant double bond transposition reaction. The C15 and C23 stereogenic centers were created using catalytic asymmetric reactions. The trisubstituted and trans-disubstituted alkenes were created stereoselectively by taking advantage of ring-closing metathesis and the Julia-Kocienski olefination reaction, respectively. Georg Thieme Verlag Stuttgart, New York.
- Raghavan, Sadagopan,Samanta, Pradip Kumar
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p. 1983 - 1987
(2013/09/24)
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- Stereoselective total synthesis of paecilomycin e
-
First total synthesis of recently isolated resorcylic acid lactone paecilomycin E has been accomplished. The key reactions include olefin metathesis, Mitsunobu reaction, Stille coupling and regioselective allylation.
- Srihari,Mahankali,Rajendraprasad
-
-
- An efficient chiral-pool synthesis of botryolide-E
-
An efficient stereoselective total synthesis of botryolide-E by a chiral-pool approach is described. 2012 Elsevier Ltd. All rights reserved.
- Madabhushi, Sridhar,Godala, Kondal Reddy,Beeram, China Ramanaiah,Chinthala, Narsaiah
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p. 5539 - 5540
(2012/11/07)
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- On the origins of diastereoselectivity in the conjugate additions of the antipodes of lithium N-benzyl-(N-α-methylbenzyl)amide to enantiopure cis- and trans-dioxolane containing α,β-unsaturated esters
-
"Matching" and "mismatching" effects in the doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-(N-α-methylbenzyl)amide to enantiopure cis- and trans-dioxolane containing α,β-unsaturated esters have been investigated. High levels of substrate control were established first upon conjugate addition of achiral lithium N-benzyl-N-isopropylamide to both tert-butyl (S,S,E)-4,5-O- isopropylidene-4,5-dihydroxyhex-2-enoate and tert-butyl (4R,5S,E)-4,5-O- isopropylidene-4,5-dihydroxyhex-2-enoate. However, upon conjugate addition of lithium (R)-N-benzyl-(N-α-methylbenzyl)amide and lithium (S)-N-benzyl-(N-α-methylbenzyl)amide to these substrates, neither reaction pairing reinforced the apparent sense of substrate control. These reactions do not, therefore, conform to the classical doubly diastereoselective "matching" or "mismatching" pattern usually exhibited by this class of reaction. A comparison of these reactions with the previously reported doubly diastereoselective conjugate addition reactions of lithium amide reagents to analogous substrates is also discussed.
- Davies, Stephen G.,Foster, Emma M.,Frost, Aileen B.,Lee, James A.,Roberts, Paul M.,Thomson, James E.
-
supporting information; experimental part
p. 6186 - 6200
(2012/09/05)
-
- Synthesis of the C3-14 fragment of palmerolide A using a chiral pool based strategy
-
Palmerolide A, a potent and selective inhibitor of melanoma cell growth, is a macrocylic polyketide isolated from the Antarctic tunicate Synoicum adareanum. Palmerolide A targets transmembrane proton pumps, the vacuolar-ATPases, and induces autophagy, but
- Lebar, Matthew D.,Baker, Bill J.
-
experimental part
p. 1557 - 1562
(2010/04/02)
-
- CYCLIC AMINE COMPOUND
-
The present invention provides an excellent antihypertensive medicament. The medicament of the present invention comprises a compound having the general formula (I) and the like: [wherein R1: H, substitutable alkyl, substitutable alkenyl, substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like; R2: H, substitutable alkyl, substitutable alkenyl, substitutable cycloalkyl or the like; R3, R4; H, substitutable alkyl, substitutable alkenyl, substitutable cycloalkyl or the like; R5, R6: H, substitutable alkyl, substitutable cycloalkyl, substitutable alkoxy or the like; R7, R8: H, substitutable alkyl, substitutable cycloalkyl or the like; X: the formula (II) or the like; A: substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like; Y: a single bond, substitutable alkylene, substitutable alkenylene, -(CH2)a-X1-(CH2)b- (X1: the formula -NH-, -O- or the like; a, b: 0-5) or the like; B: substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like].
- -
-
Page/Page column 147
(2009/04/23)
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- Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis
-
Tuberculosis is an increasing threat, owing to the spread of AIDS and to the development of resistance of the causative organism, Mycobacterium tuberculosis, to the currently available drugs. Dihydrofolate reductase (DHFR) is an important enzyme of the folate cycle; inhibition of DHFR inhibits growth and causes cell death. The crystal structure of M. tuberculosis DHFR revealed a glycerol tightly bound close to the binding site for the substrate dihydrofolate; this glycerol-binding motif is absent from the human enzyme. A series of pyrimidine-2,4-diamines was designed with a two-carbon tether between a glycerol-mimicking triol and the 6-position of the heterocycle; these compounds also carried aryl substituents at the 5-position. These, their diastereoisomers, analogues lacking two hydroxy groups and analogues lacking the two-carbon spacing linker were synthesised by acylation of the anions derived from phenylacetonitriles with ethyl (4S,5R)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate, ethyl (4S,5S)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate, tetrahydrooxepin-2-one and 2,3-O-isopropylidene-d-erythronolactone, respectively, to give the corresponding α-acylphenylacetonitriles. Formation of the methyl enol ethers, condensation with guanidine and deprotection gave the pyrimidine-2,4-diamines. Preliminary assay of the abilities of these compounds to inhibit the growth of TB5 Saccharomyces cerevisiae carrying the DHFR genes from M. tuberculosis, human and yeast indicated that 5-phenyl-6-((3R,4S)-3,4,5-trihydroxypentyl)pyrimidine-2,4-diamine selectively inhibited M. tuberculosis DHFR and had little effect on the human or yeast enzymes.
- El-Hamamsy, Mervat H.R.I.,Smith, Anthony W.,Thompson, Andrew S.,Threadgill, Michael D.
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p. 4552 - 4576
(2008/03/12)
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- First total synthesis and absolute configuration of the styryl lactone gonioheptolide A
-
Efficient asymmetric syntheses of both naturally occurring and non-naturally occurring enantiomers of gonioheptolide A are reported. The absolute configuration of (+)-gonioheptolide A was established by NOESY, Mosher ester analysis, and comparison with the specific rotation of the isolated (+)-gonioheptolide A. Georg Thieme Verlag Stuttgart.
- Gupta, Shuchi,Rajagopalan, Murali,Alhamadsheh, Mamoun M.,Tillekeratne, L. M. Viranga,Hudson, Richard A.
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p. 3512 - 3518
(2008/09/20)
-
- Synthesis and conformational and configurational studies of diastereoisomeric O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols
-
Chiral sulfoximines have applications as transition-state mimicking enzyme inhibitors, as peptide isosteres and as chiral auxiliaries in synthesis. To access the required O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols, 4S,5S-di(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (prepared from diethyl R,R-tartrate) was converted into its monobenzyl ether. Mitsunobu-like coupling with thiophenols gave 4S,5R-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylthiomethyl)-1,3-dioxolanes. Sulfoxidation and S-imination (trifluoroacetamide, iodosobenzene diacetate, rhodium acetate) proceeded without stereoselectivity, giving inseparable diastereomeric mixtures of 4S,5R,S(±)-4-(benzyloxymethyl)-2,2-dimethyl-5-(N-(trifluoroacetyl)arylsulfonimidoylmethyl)-1,3-dioxolanes. Removal of the trifluoroacetyl protection allowed chromatographic separation of the diastereomeric 4S,5R,S(±)-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylsulfonimidoylmethyl)-1,3-dioxolanes. The configurations at sulfur were determined by X-ray crystallography and some analysis of the solution and solid-state conformations was carried out. The resulting O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols are of use in developing enzyme inhibitors.
- Kwong, Joey S.W.,Mahon, Mary F.,Lloyd, Matthew D.,Threadgill, Michael D.
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p. 12601 - 12607
(2008/03/14)
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- An efficient synthesis of (-)-posticlure: The sex pheromone of Orgyia postica
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An efficient multigram synthesis of (-)-posticlure, the first frans-epoxide sex pheromone found in Orgyia postica, from diethyl L-tartrate is described. The synthesis was completed in seven steps and 27 % overall yield. The synthetic strategy features double-Wittig olefination and a stereoselective one-pot conversion of diol to epoxide as the key steps. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Fernandes, Rodney A.
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p. 5064 - 5070
(2008/03/18)
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- Total synthesis of the proposed structure for pyragonicin
-
(Chemical Equation Presented) The total synthesis of acetogenin 1 reported for pyragonicin and its 10-epimer 32 is described. The common THP ring system was stereoselectively constructed through a Sml2-induced reductive cyclization of β-alkoxy
- Takahashi, Shunya,Ogawa, Narihito,Koshino, Hiroyuki,Nakata, Tadashi
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p. 2783 - 2786
(2007/10/03)
-
- Synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphoric acid analogues as alternate substrates for methylerythritol phosphate synthase
-
(Chemical Equation Presented) Four deoxyxylulose phosphate (DXP) analogues were synthesized and evaluated as substrates/ inhibitors for methylerythritol phosphate (MEP) synthase. In analogues CF3-DXP (1), CF 2-DXP (2), and CF-DXP (3)
- Fox, David T.,Poulter, C. Dale
-
p. 1978 - 1985
(2007/10/03)
-
- Synthesis and biological evaluation of new cross-conjugated dienone marine prostanoid analogues
-
The synthesis of a series of brominated cross-conjugated dienones, marine prostanoid analogues, was considered using two cyclopentannelation processes, from enamine (by a domino 3-aza Claisen/Mannich reaction) and from dioxolane ester alkylation followed by intramolecular Wittig reaction. All the compounds synthesized featured the same cross-conjugated dienone system, with a vicinal syn or anti diol on the ω-chain. The replacement of the ω-side-chain of the natural prostanoids with a 1-hydroxyphenyl-butyl moiety gave new prostanoids (32-34) with good cytotoxicities. In a second series of products, the possibility of a shorter α-side-chain bearing a simple phenyl ester was investigated. The results indicated a dramatic increase in the cytotoxicity (39, 40, 43, 44). Finally, in a third series, the ω- 1-hydroxyphenyl-butyl was replaced by a 1-hydroxymethyloxybenzyl chain. These simpler compounds (45,46,47,48, 60) are still highly cytotoxic, in the medium range of 60 nM, close to the value of natural punaglandins.
- Kuhn, Cyrille,Roulland, Emmanuel,Madelmont, Jean-Claude,Monneret, Claude,Florent, Jean-Claude
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p. 2028 - 2039
(2007/10/03)
-
- Enantiocontrolled synthesis of 3-pyrrolines from α-amino allenes
-
Cyclization of α-amino allenes in the presence of N-bromosuccinimide afforded pyrrolines in good yields. The products were obtained with high enantiomeric excesses when optically active allenes were used as substrates. The synthesis of a 2,5-dehydroprolinol derivative is also presented. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Horvath, Attila,Benner, Jessica,Baeckvall, Jan-E.
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p. 3240 - 3243
(2007/10/03)
-
- Mild and efficient palladium(II)-catalyzed racemization of allenes
-
Allenes undergo racemization in the presence of catalytic amounts of Pd(OAc)2/LiBr under mild conditions; the reaction proceeds via a bromopalladation-debromopalladation sequence and tolerates various functional groups.
- Horvath, Attila,Baeckvall, Jan-E.
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p. 964 - 965
(2007/10/03)
-
- A facile synthesis of enantiopure tricyclic furanyl and pyranyl derivatives via tungsten-mediated cycloalkenation and Diels-Alder reaction
-
We report the synthesis of chiral furanyl and pyranyl dienes 1 and 2 based on cycloalkenation of chiral tungsten alkynol complexes. These two dienes bear a chiral 1,3-dioxolane group to control diastereoselective Diels-Alder reactions with electron-deficient olefins. The chiral 1,3-dioxolane substituents of the cycloadducts were degraded into hydrogen atoms to make these molecules possess common furan and pyran rings. Dienes 1 and 2 are good building blocks for enantiopure forms of tricyclic oxygen compounds.
- Huang, Heh-Lung,Liu, Rai-Shung
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p. 805 - 810
(2007/10/03)
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- Facile synthesis of enantiopure tricyclic furanyl derivatives via tungsten-mediated cycloalkenation reactions and Diels-Alder reactions
-
Chiral furanyl diene 1 is easily prepared from cycloalkenation of chiral tungsten alkynol with acetaldehyde, followed by demetalation with Me3NO. This diene bears a chiral 1,3-dioxolane group to control diastereoselective Diels-Alder reactions
- Huang, Heh-Lung,Huang, Heh-Chang,Liu, Rai-Shung
-
p. 7983 - 7985
(2007/10/03)
-
- Formal synthesis of (+)-isolaurepinnacin
-
The stereoselective formal synthesis of (+)-isolaurepinnacin is described. The required key oxepene skeleton possessing cis-oriented alkyl substituents at the α,ω-positions was stereoselectively constructed via the cyclization of the corresponding hydroxy epoxide promoted by the (Bu3Sn)2O/Zn(OTf)2 system.
- Suzuki, Toshio,Matsumura, Ryuji,Oku, Ken-ichi,Taguchi, Keiichi,Hagiwara, Hisahiro,Hoshi, Takashi,Ando, Masayoshi
-
-
- Synthesis of carba sugars from aldonolactones. Part IV. Stereospecific synthesis of carbaheptopyranoses by radical-induced carbocyclisation of 2,3-unsaturated octonolactones
-
Three new carbaheptopyranoses, 6-deoxy-5a-carba-β-L-gulo- (8), 5a-carba-D-glycero-β-D-ido- (22) and 5a-carba-Lglycero-α-L-galacto-heptopyranose (25), have been prepared from 8-bromo-8-deoxy-2,3-unsaturated octono-1,4-lactones with L-galacto-, D-gluco- and D-manno-configuration, respectively. The key step was a regio- and stereoselective 6-exo-trig radical-induced carbocyclisation of the unsaturated octonolactones to give bicyclic cyclohexane-lactone derivatives. Reduction of the lactone moiety using Ca(BH4)2 gave the said carbaheptopyranoses. The 8-bromo-8-deoxy-2,3-unsaturated octonolactones were prepared from the inexpensive, commercially available D-glycero-D-gulo-heptonolactone and L-tartaric acid.
- Wagner, Sussi Holstein,Lundt, Inge
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p. 780 - 788
(2007/10/03)
-
- Structure elucidation and synthesis of (4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide [(S,S)-sapinofuranoue B]-a novel γ-lactone metabolite of acremonium strictum
-
The structure of (4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide, a novel metabolite of Acremonium strictum, has been established by spectroscopic studies and chemical correlation with the known L-factor. The structure has been confirmed by a total synthesis in which the asymmetric centres at C-4 and C-5 were elaborated from dimethyl L-tartrate and the 6,8-diene moiety was introduced via Stille coupling of (E)-prop-1-enyltributyltin with a (Z)-vinylic iodide. The absolute configurations of sapinofuranones A and B, recently isolated metabolites of Sphaeropsis sapinae, are shown to be the corresponding (4R,5S) and (4R,5R) diastereomers of the A. strictum metabolite.
- Clough, Sarah,Raggatt, Mairi E.,Simpson, Thomas J.,Wills, Christine L.,Whiting, Andrew,Wrigley, Stephen K.
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p. 2475 - 2481
(2007/10/03)
-
- Total synthesis of everninomicin 13,384-1 - Part 2: Synthesis of the FGHA2 fragment
-
The stereoselective synthesis of everninomicin's 13,384-1 (1) FGHA2 fragment (2) in a suitable form for incorporation into the final target (1) is described. The construction of the FG 1,1′-disaccharide linkage relied on a new method based on tin-acetal chemistry, while for the GH orthoester bridge, a number of approaches were explored. Final success for the latter construction came when a novel 1,2-phenylseleno migration reaction was applied to couple rings G and H, followed by ketene acetal and orthoester formation.
- Nicolaou,Mitchell, Helen J.,Fylaktakidou, Konstantina C.,Rodriguez, Rosa Maria,Suzuki, Hideo
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p. 3116 - 3148
(2007/10/03)
-
- Chiral resolution and stereospecificity of 6-phenyl-4-phenylethynyl- 1,4-dihydropyridines as selective A3 adenosine receptor antagonists
-
Racemic 6-phenyl-4-phenylethynyl-1,4-dihydropyridine derivatives have been shown to be highly selective A3 adenosine receptor antagonists (Jiang et al. J. Med. Chem. 1997, 40, 2596-2608). Methods for resolving the optical isomers at the C4 position, involving selective crystallization or chromatographic separation of diastereomeric ester derivatives, have been developed. Optically pure glycerol and threitol derivatives were used as chiral auxiliary groups for ester formation at the 3-position, resulting in diastereomeric mixtures of dihydropyridines. Esterification of a 6-phenyl-4- phenylethynyl-1,4-dihydropyridine derivative at the 3-position with a chiral, protected glycerol moiety, (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol, allowed the selective crystallization of a pure diastereomer, 9. The 1H NMR spectrum of 9 using the lanthanide shift reagent Eu(fod)3 indicated optical purity, and the (4S,2'R)-configuration was assigned using X-ray crystallography. The noncrystalline (4R,2'R)-isomer 10 was also isolated and shown to be 3-fold more potent than the (4S,2'R)-isomer in binding to A3 receptors. The 2,2-dimethyl-1,3-dioxolane moiety also served as a protected form of a diol, which showed selective reactivity versus a 5-ethyl ester in basic transesterification reactions. A racemic 5-carboxylic acid derivative could not be resolved through crystallization of diastereomeric salts. Enantiomers of 5-benzyl 3-ethyl 2-methyl-6-phenyl-4-phenylethynyl-1,4- dihydropyridine-3,5-dicarboxylate (2) were obtained via an ester derived from (4R,5R)-(-)-2,3-O-isopropylidene-D-threitol at the 3-position, which was resolved using HPLC, and each diastereomer was subsequently deprotected in acidic conditions. The resulting diols were exchanged for ethyl ester groups by base-catalyzed transesterification. The binding of pure enantiomers of 2 at A3 adenosine receptors indicated a 35-fold stereoselectivity for the (4S)-isomer 21. A receptor docking hypothesis, using a previously derived human A3 receptor model, shows the bulkier of the two ester groups (5-Bn) of 21 oriented toward the exofacial side and the 4-position phenylethynyl group situated between transmembrane helical domain TM6 and TM7.
- Jiang, Ji-Long,Li, An-Hu,Jang, Soo-Yeon,Chang, Louis,Melman, Neli,Moro, Stefano,Ji, Xiao-Duo,Lobkovsky, Emil B.,Clardy, Jon C.,Jacobson, Kenneth A.
-
p. 3055 - 3065
(2007/10/03)
-
- Highly selective Silver(I) oxide mediated monoprotection of symmetrical diols
-
Treatment of symmetrical diol with Ag2O and alkyl halide gave the monoprotected derivative in good to excellent yield.
- Bouzide, Abderrahim,Sauve, Gilles
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p. 5945 - 5948
(2007/10/03)
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- Synthese des 5-desoxy-5.5.5-trifluoro-D- et -L-pentofuranoses
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Synthetic pathways leading to 5-deoxy-5,5,5-trifluoropentofuranoses are reported. The main difficulty was to obtain a good diastereoselectivity at the C-4 carbon bearing the CF3 group. For the ribose and the lyxose derivatives the problem was p
- Munier, Pascal,Giudicelli, Marie-Beatrice,Picq, Dominique,Anker, Daniel
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p. 739 - 762
(2007/10/03)
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- Synthetic Studies toward Mono-THF Annonaceous Acetogenins; A Diastereoselective and Convergent Approach to Corossolone and (10RS)-Corossoline
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This paper describes a diastereoselective approach to the total syntheses of both corossolone (1) and (10RS)-corossoline (2), two naturally occurring cytotoxic annonaceous acetogenins from Annona muricata. 2,3-O-Isopropylidene-D-threitol (3) has been used
- Yao, Zhu-Jun,Wu, Yu-Lin
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p. 1170 - 1176
(2007/10/02)
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- Efficient Intramolecular C-H Insertion by an Alkylidene Carbene Generated from a Vinyl Chloride
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It is observed that chloride 4 on exposure to sodium bis(trimethylsilyl)amide smoothly generates the cyclopentene 5, by insertion of the intermediate alkylidene carbene into the methine C-H.Chloride 4 is prepared in several steps from L-tartaric acid.On ozonolysis and subsequent aldol condensation, 5 is transformed into 1, a synthon for the A ring of taxol 2.
- Taber, Douglass F.,Sahli, Ayman,Yu, Han,Meagley, Robert P.
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p. 6571 - 6573
(2007/10/03)
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- Transglucosylation with 6′-chloro-6′-deoxysucrose and immobilized isomaltulose-producing microorganisms using 2,2-dimethyl-1,3-dioxolane-4-methanol and its related compounds as acceptors. Steric and chemical requirement of the glucosyl acceptor
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Enantioselective and diastereoselective α-D-glucosylation of 2,3-O-isopropylidene-erythritol was observed in transglucosylation with a synthetic donor using three kinds of immobilized isomaltulose-producing microorganisms. Several related compounds, including an 2,3-O-isopropylidenated aldotetrose dimethyl dithioacetal and an aldotetronic acid ester were also glucosylated in moderate or good yield, depending on the microorganism utilized. Steric as well as functional group factors are discussed in relation to the substrate specificity of the glucosyl acceptor.
- Kakinuma,Tsuchiya,Tanaka,Horito,Hashimoto
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p. 237 - 251
(2007/10/02)
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- Synthesis of Carbohydrates and Related Polyhydroxylated Compounds Employing Asymmetric Dihydroxylation. 1. An Access to Erythro-diols
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Asymmetric dihydroxylation provides an easy access to tetrose: threose directly from the (E)-olefin 1, and erythrose via an irreversible Payne-type rearrangement - opening process of the threitol cyclic sulfate 5.
- Ko, Soo Y.,Malik, Majbeen
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p. 4675 - 4678
(2007/10/02)
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- Synthesis of efficient chiral bisphosphine ligands, modified DIOPs, (4R,5R)-4-(Diaryl- or dialkylphosphino)methyl-5-(diarylphosphino)methyl-2,2- dimethyl-1,3-dioxolanes, and their use in rhodium(I)-catalyzed asymmetric hydrogenations
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Modified DIOPs, (4R,5R)-4-(diaryl- or dialkyphosphino)methyl-5- (diarylphosphino)methyl-2,2-dimethyl-1,3-dioxolanes, were prepared on the basis of our design concept, and used as ligands for the rhodium(I)-catalyzed asymmetric hydrogenations of ketopantolactone, itaconic acid, dimethyl itaconate, and β-aryl-substituted itaconic acid derivatives. A neutral rhodium(I)-complex of (4R-trans)-dicyclohexyl[[5- [(diphenylphosphino)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]phosphine (DIOCP) bearing both a dicyclohexylphosphino group and a diphenylphosphino group was found to be a more efficient catalyst than the original DIOP in the asymmetric hydrogenation of ketopantolactone. Modified DIOPs bearing electron-donating groups at their para positions were efficient ligands for the rhodium(I)-catalyzed assymetric hydrogenations of itaconic acid and its derivatives; in particular, (4R-trans)-[(2,2-dimethyl-1,3-dioxolane-4,5- diyl)bis(methylene)]bis[bis(4'-methoxy-3',5'-dimethylphenyl)phosphine] (MOD- DIOP) bearing both a p-methoxy group and two m,m'-methyl groups on each phenyl group showed much higher enantioselectivity and catalytic activity than DIOP.
- Morimoto,Chiba,Achiwa
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p. 1149 - 1156
(2007/10/02)
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- An acyl radical initiated tandem 7-endo/5-exo radical cyclization approach to enantiomerically pure bicyclo[5.3.0]decan-2-ones
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The preparation of acetonide derivatives of erythro and threo 4,5-dihydroxyhept-6-enoic acids from the chiral pool is described. The phenylseleno esters derived from these acids undergo cyclization with tributyltin hydride to give mixtures of cyclohexanones and cycloheptanones. The inclusion of the appropriate four carbon side chain at C-7 leads, via a tandem radical cyclization process, to the title compounds in moderate yield.
- Batty,Crich
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p. 875 - 878
(2007/10/02)
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- Acyl Radical Cyclization in Synthesis. Part 4. Tandem Processes: The 7-endo/5-exo Serial Cyclization Approach to Enantiomerically Pure Bicyclodecan-2-ones
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Two diastereoisomeric phenylselenoesters of 4,5-dihydroxyhept-6-enoic acid were prepared as their acetonide derivatives from the chiral pool.On treatment with tributyltin hydride and azoisobutyronitrile the erythro isomer cyclized to give meso-4,5-dihydroxycycloheptanone, as its acetonide, in moderate yield whereas under the same conditions the threo-isomer gave a much lower yield of the corresponding C2-symmetric ketone.In the erythro-series an alkyl group at C-7 of the heptenoyl system was found to retard significantly the direct endo-mode cyclisation; however, the cycloheptanone could still be obtained by a rearrangement when the tin hydride concentration was kept to a minimum.A tandem 7-endo/5-exo cyclization system was then constructed and tested, resulting in the formation of all four possible diastereoisomeric biyclodecanones.Further model studies were conducted on the effect of alkyl and alkoxy substituents at C-5 of the heptenoyl radical system on the mode of cyclisation.Alkyl substituents exert a steric effect whilst alkoxy substituents also have a stereoelectronic effect.
- Batty, Duncan,Crich, David
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p. 3193 - 3204
(2007/10/02)
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- Synthesis of a novel four-carbon chiron - (R)-1-t-butyldimethylsilyl-3,4-epoxy-but-1-yne
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A simple and efficient synthesis of the novel chiron-(R)-1-TBDMS-3,4-epoxy-but-1-yne has been developed starting from a derivative of (R,R)-(-)-tartaric acid. A new stereoselective bromination reaction of an O-silyl ether with BBr3 is also described.
- Lopp,Kanger,Muraus,Pehk,Lille
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p. 943 - 944
(2007/10/02)
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- High Diastereofacial Differentiation in Osmium Tetraoxide Catalyzed Dihydroxylation of Acyclic Bis-allylic Compounds
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Bis-allylic compounds such as diethyl (4S,5S)-4,5-bis(tert-butyldimethylsilyl)oxy)-2,6-octadienedioate (1a) exhibit very high diastereoselection in osmiumtetraoxide catalyzed dihydroxylation; a particular ground-state conformation is proposed to be respon
- Saito, Seiki,Morikawa, Yasuhisa,Moriwake, Toshio
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p. 5424 - 5426
(2007/10/02)
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- Syntheses of Unsaturated Trihydroxy C-18 Fatty Acids Isolated from Rice Plants Suffering from Rice Blast Disease
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Two trihydroxy unsaturated C-18 fatty acids isolated from rice plants as agents with activity against blast disease were synthesized from (+)-dimethyl tartrate.Keywords: methyl (9S,12S,13S)-trihydroxyoctadeca-10E,15Z-dienoate; methyl (9S,12S,13S)-trihydroxy-10E-octadecenoate; rice blast disease; fetal calf aorta; (+)-dimethyl tartrate; Wittig-Horner reaction
- Suemune, Hiroshi,Harabe, Tetsuji,Sakai, Kiyoshi
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p. 3632 - 3637
(2007/10/02)
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- Total synthesis of (+)-colletodiol from (S,S)-tartrate and (R)-3-hydroxybutanoate
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The macrodiolide antibiotic (+)-colletodiol (7, Scheme 1) was synthesised.The configuration was thus proven to be (6R,11R,12R,14R). - Key intermediates (Schemes 9 and 10) are the two hydroxy acids 43 and 64, which were prepared from dimethyl (S,S)-tartrate in 20percent overall yield (12 steps) and from (R)-3-hydroxybutanoate in 57percent overall yield (6 steps), respectively.The two hydroxy acids were cyclised to give, after deprotection, the title compound. - Our investigations led to the production of a large number of chiral building blocks, many of them in different stereoisomeric forms.
- Schnurrenberger, Peter,Hungerbuehler, Ernst,Seebach, Dieter
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p. 733 - 744
(2007/10/02)
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- THE CHEMISTRY OF SILYLATED KETENE ACETALS: AN EFFICIENT STEREOCONTROLLED SYNTHESIS OF N-BENZOYL L-DAUNOSAMINE
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N-Benzoyl L-daunosamine was synthesized with high stereoselectivity utilizing a 1,3-addition of ketene silyl acetal (3a) to the chiral nitrone, (Z)-((4R)-trans-2,2,5-trimethyl-1,3-dioxolan-4-yl)methylene((1S)-1-phenylethyl)amine N-oxide (4c) accompanied by a silyl group-transfer in acetonitrile under mild conditions.
- Kita, Yasuyuki,Itoh, Fumio,Tamura, Osamu,Ke, Ya Yuan,Tamura, Yasumitsu
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p. 1431 - 1434
(2007/10/02)
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- STEREOCONTROLLED TOTAL SYNTHESIS OF THE MACROCYCLIC LACTONE (-)-ASPICILIN
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The essential features of the enantiocontrolled total synthesis of (-)-aspicilin are the strategic use of the photochemical rearrangement of α,β-epoxy diazomethyl ketones to 4-hydroxyalkenoates (Scheme 1) and the stereochemical control of the Sharpless epoxidation, α,ο functionalization of an alkynol using potassium 3-aminopropylamine (KAPA) as acetylene zipper, coupling between C7 and C8 by means of a Wittig reaction and lactonization by using 2,6-dichlorobenzoyl chloride.
- Waanders, P.P.,Thijs, L.,Zwanenburg, B.
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p. 2409 - 2412
(2007/10/02)
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- SYNTHESIS AND APPLICATION OF A NOVEL BISPHOSPHINE LIGAND, (-)-DIOCP, AS AN UNSYMMETRIZED DIOP TO PROVE THE GENERAL UTILITY OF NEW DESIGNING CONCEPT.
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A new chiral bisphosphine-Rh complex (DIOCP-Rh) was found to show excellent catalytic activity and good enantioselectivity for the asymmetric hydrogenation of ketopantolactone proving the general utility of new designing concept.
- Chiba, Mitsuo,Takahashi, Hitoe,Takahashi, Hisashi
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p. 3675 - 3678
(2007/10/02)
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- Biomimetic Studies Using Artificial Systems. II. Enantioselective Thiolysis of D- or L-α-Amino Acid Ester Salts by Thiol-Bearing Chiral Crown Ethers as an Enzyme Model
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The rates of transacylation were studied between thiol-bearing chiral crown ethers (1-10) and α-amino acid p-nitrophenyl ester salts.Enantioselectivities, kD/kL ratios, of 6.5 for valine ester salt, 8.7 for phenylalanine ester salt, and 7.7 for valine ester salt were achieved by 1, 5, and 8, respectively.Saturation phenomena of rate acceleration depending on crown concentration were observed and analysis of these data revealed that the chiral recognition occurs in the step of liberation of p-nitrophenol by intra-complex thiolysis, not in the complex-forming step.A possible mechanism for the anantioselectivity is proposed on the basis of the kinetic data.Keywords - crown ether; transacylation; pseudo-first-order rate constant; enantioselectivity; thiolysis; intra-complex reaction; enzyme model
- Sasaki, Shigeki,Kawasaki, Motoji,Koga, Kenji
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p. 4247 - 4266
(2007/10/02)
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- (+)-COLLETODIOL SYNTHESIS FROM (S,S)-TARTARIC ACID AND (R)-HYDROXY-BUTYRIC ACID
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E-(R)-5-Hydroxy-2-hexenoic acid (4) and the acetonide of E-(4R,5R,7R)-trihydroxy-2-octenoic acid (3) are joined to give, after deprotection, (+)-colletodiol (1).The syntheses of the two hydroxy-acids from poly-(R)-3-hydroxy-butenoate (PHB) and (-)-tartaric acid, respectively, are outlined.
- Schnurrenberger, Peter,Hungerbuehler, Ernst,Seebach, Dieter
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p. 2209 - 2212
(2007/10/02)
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