- Structural and Functional Analysis of Bacterial Sulfonosphingolipids and Rosette-Inducing Factor 2 (RIF-2) by Mass Spectrometry-Guided Isolation and Total Synthesis
-
We have analyzed the abundance of bacterial sulfonosphingolipids, including rosette-inducing factors (RIFs), in seven bacterial prey strains by using high-resolution tandem mass spectrometry (HRMS2) and molecular networking (MN) within the Glob
- Beemelmanns, Christine,Jautzus, Theresa,King, Nicole,Leichnitz, Daniel,Peng, Chia-Chi,Ragu?, Luka,Regestein, Lars,Rutaganira, Florentine U. N.
-
supporting information
(2022/01/04)
-
- Preparation method of alpha-hydroxyl-gamma-butyrolactone
-
The invention belongs to the field of preparation of organic compounds, and provides a preparation method of alpha-hydroxyl-gamma-butyrolactone. The method is characterized in that malic acid is used as a raw material, and alpha-hydroxyl-gamma-butyrolactone is synthesized with high yield through four steps of reactions, namely, carboxyl and alpha-hydroxyl protection, beta-carboxyl reduction, protecting group removal and internal esterification. The method has the advantages of easily available raw materials, mild reaction conditions and low cost, and is suitable for large-scale preparation of alpha-hydroxy-gamma-butyrolactone.
- -
-
Paragraph 0020; 0021
(2021/06/13)
-
- A Unified Approach to Phytosiderophore Natural Products
-
This work reports on the concise total synthesis of eight natural products of the mugineic acid and avenic acid families (phytosiderophores). An innovative ?east-to-west“ assembly of the trimeric products resulted in a high degree of divergence enabling the formation of the final products in just 10 or 11 steps each with a minimum of overall synthetic effort. Chiral pool starting materials (l-malic acid, threonines) were employed for the outer building blocks while the middle building blocks were accessed by diastereo- and enantioselective methods. A highlight of this work consists in the straightforward preparation of epimeric hydroxyazetidine amino acids, useful building blocks on their own, enabling the first synthesis of 3’’-hydroxymugineic acid and 3’’-hydroxy-2’-deoxymugineic acid.
- Kratena, Nicolas,G?kler, Tobias,Maltrovsky, Lara,Oburger, Eva,Stanetty, Christian
-
supporting information
p. 577 - 580
(2020/11/02)
-
- Synthesis of Saxitoxin and Its Derivatives
-
The chiral synthesis of (+)-saxitoxin and its derivatives is described. Two consecutive carbon-nitrogen bonds at C-5 and C-6 in saxitoxin were effectively installed by the sequential Overman rearrangement of an allylic vicinal diol derived from d-malic acid. The bicyclic guanidine unit was constructed by the intramolecular aminal formation of an acyclic bis-guanidine derivative possessing a ketone carbonyl at C-4. From the bicyclic aminal intermediate, (+)-saxitoxin, (+)-decarbamoyl-β-saxitoxinol [(+)-dc-β-saxitoxinol], and the unnatural skeletal isomer, (-)-iso-dc-saxitoxinol, were synthesized.
- Chida, Noritaka,Kinoshita, Kyoko,Mukai, Shori,Okamoto, Ryosuke,Okuyama, Yuya,Sato, Takaaki
-
supporting information
(2020/11/13)
-
- L-malic acid dimer impurity and preparation method thereof
-
The invention provides an L-malic acid dimer impurity and a preparation method thereof. The L-malic acid dimer impurity (impurity X) is discovered and separated for the first time, and has a structureshown in the specification. The preparation method of the impurity X comprises the following steps: (1) protecting a carboxyl group at one side of L-malic acid to obtain a compound 1; (2) protectinga carboxyl group at the other side of the compound 1 to obtain a compound 2; (3) hydrolyzing the compound 2 under the condition of acetic acid/water/tetrahydrofuran to obtain a compound 3; (4) dehydrating and condensing the compound 3 to obtain a compound 4; and (5) hydrogenating the compound 4 to remove benzyl groups to obtain the impurity X. The impurity spectrum of malic acid stability researchis expanded, and the improvement of the malic acid quality standard is promoted. The compound property of the L-malic acid dimer impurity is studied, and the L-malic acid dimer impurity has positiveguiding significance for selection of storage conditions of malic acid.
- -
-
Paragraph 0025; 0038-0040; 0046-0048; 0053-0055; 0060-0062
(2020/05/02)
-
- Synthesis and structure reassignment of malylglutamate, a recently discovered earthworm metabolite
-
Malylglutamate, a newly identified metabolite in earthworms, was synthesized using a traditional peptide coupling approach for assembling the amide from protected malate and glutamate precursors. The proposed structure (1) and a diastereomer were synthesized, but their NMR spectra did not match the natural sample. Further analysis of the natural sample using HMBC spectroscopy suggested an alternative attachment of the malyl moiety, and β-malylglutamate (2) diastereomers were synthesized, L,L-2 and D,D-2. NMR spectra were an excellent match with the natural sample, and chiral-phase chromatography was employed to identify (a)-β-l-malyl-l-glutamate (2) as the isomer native to Eisenia fetida.
- Griffith, Corey M.,Feceu, Abigail,Larive, Cynthia K.,Martin, David B. C.
-
p. 417 - 421
(2019/02/19)
-
- METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
-
Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.
- -
-
Paragraph 0116; 0117
(2016/11/28)
-
- STIMULUS-RESPONSIVE POLY(LACTIC-CO-GLYCOLIC)-BASED POLYMERS AND NANOPARTICLES FORMED THEREFROM
-
PLGA-based polymers include pendant nucleophiles protected with photocleavable protecting groups. Upon deprotection, the polymers degrade rapidly via intramolecular cyclization into small molecules. The polymer may be formulated as a nanoparticle, with an encapsulated payload, which may be an imaging agent, a bioactive agent or a pharmaceutical agent.
- -
-
Page/Page column 11; 13
(2016/12/12)
-
- Light-triggered intramolecular cyclization in poly(lactic- co -glycolic acid)-based polymers for controlled degradation
-
Polylactide (PLA) and poly(dl-lactide-co-glycolide) (PLGA) are two prominent FDA-approved polymers because of their useful biodegradation into largely innocuous substances. Their hydrolytic degradation is slow and offers minimal control over degradation kinetics, especially in the minutes time scale. However, molecular engineering of their structures could allow triggered degradation. We have synthesized, by ring-opening polymerization (ROP), a series of PLGA-based polymers containing pendant nucleophiles protected with photocleavable groups. Upon deprotection, two of the polymers degrade rapidly via intramolecular cyclization into small molecules. Nanoparticles formulated from these polymers undergo rapid structural changes in response to UV light. This work introduces a novel polymeric structure to enable rapid on-demand degradation and expands the library of polymers that degrade by cyclization.
- Olejniczak, Jason,Chan, Minnie,Almutairi, Adah
-
p. 3166 - 3172
(2015/06/08)
-
- SYNTHETIC PRECURSOR OF EPOTHILONE FOR IMPROVING PRODUCTION OF EPOTHILONE AND METHOD FOR PREPARING EPOTHILONE USING THE SAME
-
The present invention relates to a compound for increasing production of epothilone in actinomyces, and to a method for producing epothilone with increased yield. The method for producing epothilone of the present invention includes a step of culturing actinomyces in which epothilone-biosynthesizing genes in Sorangium cellulosum including epoD, epoE, epoF, orf6, orf3, and orf14 are introduced in a culture medium. According to the present invention, it is possible to increase the production yield of epothilone in actinomyces, even in actinomyces in which epoA, epoP, epoB, and epoC are not introduced therein.COPYRIGHT KIPO 2016
- -
-
Paragraph 0071; 0072; 0073
(2016/10/10)
-
- PROCESS FOR THE PREPARATION OF (1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMETHYL-3-[(1E)-1-METHYL-2-(2-METHYL-4-THIAZOLYL)ETHENYL]-17-OXA-4-AZABICYCLO[14.1.0]HEPTADECANE-5,9-DIONE AND INTERMEDIATES THEREOF
-
The present invention relates to an improved process for the preparation of (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2- methyl-4-thiazolyl)ethenyl]- 17-oxa-4-azabicyclo[ 14.1.0]heptadecane-5,9-dione represented by the following structural formula I and intermediates thereof. The present invention also provides novel intermediate compounds useful for the preparation of compound of formula I and its intermediates.
- -
-
Page/Page column 38-39
(2015/06/25)
-
- Water-soluble prodrugs of paclitaxel containing self-immolative disulfide linkers
-
A new series of disulfide-containing prodrugs of paclitaxel were designed, synthesized and evaluated against 6 cancer cell lines. Some of these prodrugs exhibited nearly equal or slightly better anticancer activity when compared to that of paclitaxel. These prodrugs contain water-soluble groups such as amino, carboxyl, hydroxyl, amino acids, etc., and exhibited 6-140 fold increase in aqueous solubility when compared to paclitaxel. One of these prodrugs exhibited improved water solubility, better in vitro anticancer activity and significantly superior oral bioavailability in mice when compared to those of paclitaxel. Thus, we have identified a very promising lead compound for further optimization and evaluation as a potentially bioavailable water-soluble prodrug of paclitaxel.
- Gund, Machhindra,Khanna, Amit,Dubash, Nauzer,Damre, Anagha,Singh, Kishore S.,Satyam, Apparao
-
p. 122 - 127
(2015/02/19)
-
- MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES
-
Provided are compounds of Formula I and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.
- -
-
Page/Page column 238; 239
(2014/01/08)
-
- Organocatalytic syn-aldol reactions of hydroxy ketones with (S)-isoserinal: Asymmetric synthesis of 6-deoxy-1,5-iminohexitols and related compounds
-
An improved and convenient preparation of protected (S)-isoserinal on a large scale is reported. This key intermediate was reacted through organocatalyzed aldol reaction or Wittig based chain extension and functionalization to give enantiopure 1,5,6-trideoxy-1,5-imino-hexitols such as 10a (L-manno) and 10b (D-gluco). These two compounds are of interest as glycosidase inhibitors. The elaborated organocatalytic process includes diastereoselective syn aldol reaction of (S)-isoserinal hydrate and hydroxyacetone or 1-hydroxy-2-octanone and is promoted by various amino acid-based catalysts. Diastereoselectivities of up to 8:1 were achieved, thus establishing a new, efficient synthetic route to these important carbohydrate mimics. A novel protocol for the preparation of 1,5,6-trideoxy-1,5-imino-L- mannitol and 1,5,6-trideoxy-1,5-imino-D-glucitol is reported. The key steps include organocatalyzed syn-selective direct aldol reaction of hydroxyacetone and CBz-protected isoserinal hydrate, followed by reductive amination/ cyclization. Copyright
- Nicolas, Cyril,Pluta, Roman,Pasternak-Suder, Monika,Martin, Olivier R.,Mlynarski, Jacek
-
p. 1296 - 1305
(2013/04/10)
-
- Modular and stereoselective synthesis of tetrasubstituted helical alkenes via a palladium-catalyzed domino reaction
-
A highly modular and stereoselective synthesis of tetrasubstituted helical alkenes is accomplished by a Pd-catalyzed norbornene-mediated domino reaction. This protocol features the rapid assembly of four C-C bonds via sequential C-H activations and carbopalladations along with efficient access to enantiopure bromoalkyl aryl alkyne precursors using homologative alkynylation as the key transformation. Three distinct elements of stereoselectivity were observed in the preparation of the chiral helical alkenes: retention of stereochemistry of the substrates, induced helical diastereoselectivity in the alkene formation, and the exclusive exo-facial selectivity of the norbornene incorporation.
- Liu, Hongqiang,El-Salfiti, Mohamed,Chai, David I.,Auffret, Jeremy,Lautens, Mark
-
supporting information; scheme or table
p. 3648 - 3651
(2012/09/08)
-
- The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments
-
Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.
- Paterson, Ian,Anderson, Edward A.,Dalby, Stephen M.,Lim, Jong Ho,Maltas, Philip,Loiseleur, Olivier,Genovino, Julien,Moessner, Christian
-
supporting information; experimental part
p. 5861 - 5872
(2012/08/28)
-
- Second-generation total synthesis of spirastrellolide F methyl ester: The alkyne route
-
Outlandish: The spiroketal embedded in spirastrellolide F methyl ester is a daring site for ring closure, yet it has allowed the power of catalytic alkyne scission and activation to be showcased (see scheme). An improved strategy for the introduction of t
- Benson, Stefan,Collin, Marie-Pierre,Arlt, Alexander,Gabor, Barbara,Goddard, Richard,Fuerstner, Alois
-
supporting information; experimental part
p. 8739 - 8744
(2011/11/06)
-
- NOVEL COMPOSITIONS FOR REDUCING A? 42 PRODUCTION AND THEIR USE IN TREATING ALZHEIMER'S DISEASE (AD)
-
Novel small molecule compounds for reduction of A? 42 production and for treatment of Alzheimer's Disease and other neurodegenerative disorders, methods of making them and pharmaceutical compositions containing them are described.
- -
-
Page/Page column 49; 50
(2011/08/08)
-
- A METHOD FOR PREPARING 4-Y9-(6-AMINOPURINE)¨-2-(S)-HYDROXYL-BUTYRIC ACID METHYL ESTER
-
The present invention discloses a novel method for preparing and purifying 4-(6-Amino-purin-9-yl)-2(S)-hydroxy-butyric acid methyl ester. The preparation started from cheap and easily available L-malic acid, which was transformed to intermediate I after s
- -
-
Page/Page column 6
(2010/10/03)
-
- Synthesis and organocatalytic ring-opening polymerization of cyclic esters derived from l-malic acid
-
The synthesis of 3-(S)-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (BMD) and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (malide) from commercially available l-malic acid is reported. Ring-opening polymerization (ROP) studies of BMD are reported showing that the controlled ROP of this monomer is possible in the absence of transesterification side reactions, despite the presence of side-chain esters, using 1-(3,5- bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and (-)-sparteine to catalyze the polymerization. The ROP of malide with this system was ineffective. Investigation of the effect of initiating species revealed that the electronic nature of the alcohol had a greater effect on the ultimate molecular weight and hence initiator efficiency than steric considerations. Deprotection of the resultant poly(BMD) using H2 and Pd/C resulted in hydrophilic poly(glycolic-co-malic acid)s (PGMAs) that were able to undergo autocatalytic degradation in dilute H2O solution such that complete degradation was observed within 6 days.
- Pounder, Ryan J.,Dove, Andrew P.
-
experimental part
p. 1930 - 1939
(2011/03/22)
-
- Organocatalytic syn-aldol reactions of dioxanones with (S)-isoserinal hydrate: Synthesis of L-deoxymannojirimycin and L-deoxyidonojirimycin
-
(Chemical Equation Presented) We report a new protocol for synthesis of L-1-deoxymannojirimycin, L-1-deoxyidonojirimycin, and the N-isopropyl derivative of the latter compound from the readily available precursors (S)-isoserinal hydrate and 2-tert-butyl-2
- Palyam, Nagarjuna,Majewski, Marek
-
supporting information; experimental part
p. 4390 - 4392
(2009/09/06)
-
- Novel glucagon receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor
-
Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closely related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a >1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperglycemia in Sprague - Dawley rats. Furthermore, the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.
- Kodra, János T.,J?rgensen, Anker Steen,Andersen, Birgitte,Behrens, Carsten,Brand, Christian Lehn,Christensen, Inger Th?ger,Guldbrandt, Mette,Jeppesen, Claus Bekker,Knudsen, Lotte B.,Madsen, Peter,Nishimura, Erica,Sams, Christian,Sidelmann, Ulla G.,Pedersen, Raymon A.,Lynn, Francis C.,Lau, Jesper
-
experimental part
p. 5387 - 5396
(2009/07/01)
-
- Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
-
Azacycloalkane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.
- -
-
Page/Page column 30
(2008/12/05)
-
- Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers
-
DZ2002 and its related stereoisomers were efficiently synthesized. The optical data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In accordance with respecti
- Zhang, Yang-Ming,Ding, Yu,Tang, Wei,Luo, Wei,Gu, Min,Lu, Wei,Tang, Jie,Zuo, Jian-Ping,Nan, Fa-Jun
-
scheme or table
p. 9212 - 9216
(2009/04/11)
-
- AMINO ACID DERIVATIVES
-
The present invention relates to a method of treating pain using a compound of formula (I), wherein Ar, R1, R3 and R3a are as defined herein. The invention also relates to certain novel compounds of formula (I).
- -
-
Page/Page column 30
(2008/06/13)
-
- AMINO ACID DERIVATIVES
-
The present invention relates to compounds of formula (I): wherein R1, R2, R4 and R4a are as defined herein. The invention also relates to the use of compounds of formula (I) for the treatment of pain.
- -
-
Page/Page column 29
(2008/06/13)
-
- A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a potent CDK2/cyclin A inhibitor
-
The synthesis of the major metabolite of a potent 3-aminopyrazole CDK2/cyclin A inhibitor is presented. A stereoconservative approach starting from malic acid was employed to construct the hydroxy-substituted pyrrolidinone moiety. In the key step of the s
- Nesi, Marcella,Borghi, Daniela,Brasca, Maria Gabriella,Fiorentini, Francesco,Pevarello, Paolo
-
p. 3205 - 3208
(2007/10/03)
-
- Total synthesis of (+)-brasilenyne. Application of an intramolecular silicon-assisted cross-coupling reaction
-
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
-
p. 12432 - 12440
(2007/10/03)
-
- Restricted conformation analogues of an anthelmintic cyclodepsipeptide
-
Six analogues of the anthelmintic cyclodepsipeptide PF1022A were prepared, each containing a small ring fused to the macrocycle to restrict the number of conformations the larger ring can adopt. It was anticipated that such conformational changes could lead to enhanced biological activity and selectivity. The analogues form two series of three members each. In one series, a carbon-based molecular bridge joins the methyl of a leucine residue with the methyl of its closest lactic acid residue to form five-, six-, and seven-membered lactam rings. In the second series, a leucine residue is replaced with five-, six-, and seven-membered nitrogen heterocycles. Decreasing the size of the small ring in the lactam series increasingly distorts the macrocycle and consistently decreases activity relative to PF1022A. In the leucine series, a similar trend is observed. Molecular modeling of PF1022A along with the analogues described herein suggests that the ability to exist in a highly symmetrical conformational state is a necessary condition for biological activity.
- Dutton, Fred E.,Lee, Byung H.,Johnson, Sandra S.,Coscarelli, Eileen M.,Lee, Pil H.
-
p. 2057 - 2073
(2007/10/03)
-
- Glucagon antagonists/inverse agonists
-
A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism, such as dyslipidemia, and obesity.
- -
-
-
- Selective MMP inhibitors having reduced side-effects
-
The subject invention pertains to matrix metalloproteinase (MMP) inhibitors that exhibit an IC50 of below 10?4M against MMP and have substantially no activity against non-MMP metalloproteinase-related events. The MMP inhibitors of the invention have reduced side-effects, especially with respect to joint pain.
- -
-
-
- Synthesis of polyhydroxylated pyrrolizidine alkaloids of the alexine family by tandem ring-closing metathesis-transannular cyclization. (+)-Australine
-
Dienes 23 and 54, prepared from epoxy alcohol 9 via oxazolidinones 15 and 51, respectively, underwent ring-closing metathesis with Grubbs's catalyst to give azacyclooctenes 26 and 55. Treatment of each azacyclooctene with m-chloroperoxybenzoic acid afforded β-epoxide 28 from 26 and α-epoxide 61 from 60. Basic hydrolysis of each of these oxazolidinones was accompanied by transannular attack at the epoxide by nitrogen, resulting in 2-(O-benzyl)-7-deoxyalexine (29) and 1,2-di-(O-benzyl)australine (62). The latter was converted to the alkaloid australine (3) upon hydrogenolysis. Attempts to effect ring-closing metathesis of dienes 37, 38, and 46 were unsuccessful, suggesting that, while one allylic oxygen substituent can be tolerated by Grubbs's catalyst, two cannot.
- White,Hrnciar
-
p. 9129 - 9142
(2007/10/03)
-
- Total Syntheses of Epothilones B and D
-
Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.
- Mulzer, Johann,Mantoulidis, Andreas,Oehler, Elisabeth
-
p. 7456 - 7467
(2007/10/03)
-
- Epsilon-lactam analogs of the anthelmintic cyclodepsipeptide PF1022A
-
Conformationally restricted analogs of the anthelmintic cyclodepsipeptide PF1022A 1 were prepared by fusing a seven-membered lactam ring onto the macrocycle. Following the preparation of cyclodepsipeptide (CDP) 2 by classical chemical methods, CDPs 2 and 3 were synthesized using solid phase methodology involving cyclization-cleavage from an oxime resin.
- Dutton, Fred E.,Byung H, Lee
-
p. 5313 - 5316
(2007/10/03)
-
- Matrix metalloproteinase inhibitors: A structure-activity study
-
Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
- Levy, Daniel E.,Lapierre, France,Liang, Weisheng,Ye, Wenqing,Lange, Christopher W.,Li, Xiaoyuan,Grobelny, Damian,Casabonne, Marie,Tyrrell, David,Holme, Kevin,Nadzan, Alex,Galardy, Richard E.
-
p. 199 - 223
(2007/10/03)
-
- Malic acid: A convenient precursor for the synthesis of peptide secondary structure mimetics
-
Syntheses of optically active ether-linked β-lactams and aza-proline analogues via 4-bromo-2-hydroxybutanoic acid esters derived from (S)- or (R)- malic acid are described. From these intermediates peptide secondary structure mimetics can be synthesized.
- Kim, Hwa-Ok,Lum, Chris,Lee, Min S.
-
p. 4935 - 4938
(2007/10/03)
-
- A new efficient synthesis of nicotianamine and 2′-deoxymugineic acid
-
Nicotianamine and 2′-deoxymugineic acid, phytosiderophores, have been efficiently synthesized, which will be suitable for large scale production of these plant physiologically important compounds. The synthetic method for 2′,3″-dideoxy-3″-oxomugineic acid was also investigated.
- Shioiri, Takayuki,Irako, Naoko,Sakakibara, Sachiko,Matsuura, Fumiyoshi,Hamada, Yasumasa
-
p. 519 - 530
(2007/10/03)
-
- Saponaceolides: Differential cytotoxicity and enantioselective synthesis of the right-hand lactone moiety
-
The enantioselective synthesis of the right-hand lactone moiety 5 of saponaceolide B, 2, is described. The mean graph profiles of 5 do not match the characteristic patterns of differential cytotoxicity of saponaceolides A, 1, and B, 2, in the NC1 human disease-oriented tumor screening panel, pointing out the need of the entire saponaceolide structure for maintaining the specificity and potency of the antitumor activity. En route to 5 several useful chiral building blocks, such as compounds 6, 10, 19, 27, and 28 were prepared.
- Vidari,Lanfranchi,Sartori,Serra
-
p. 2977 - 2990
(2007/10/03)
-
- Stereochemistry of remote dianion addition to imines. Application to the synthesis of (1S, 8aS)-1-hydroxyindolizidine
-
A stereoselective route to (1S, 8aS)-1-hydroxyindolizidine is reported herein that incorporates as a pivotal step the diastereoselective addition of the dianion of 4-(phenylsulfonyl)butanoic acid (4-PSBA) to a chiral α-benzyloxymethyl imine.
- Green, Diana L. C.,Kiddle, James J.,Thompson, Charles M.
-
p. 2865 - 2874
(2007/10/02)
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- SYNTHESIS OF POTENTIAL TRANSITION STATE INHIBITORS OF SUCCINYL CoA:TETRAHYDRODIPICOLINATE N-SUCCINYLTRANSFERASE
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The preparation of 2-hydroxytetrahydropyran-2,6-dicarboxylic acid (6S-1), 2-hydroxytetrahydrofuran-2,5-dicarboxylic acid (17), and 3,3-difluoro-2-hydroxytetrahydropyran-2,6-dicarboxylic acid (26), three transition state analogs of hydrated tetrahydrodipic
- Roberts, John L.,Borgese, Jack,Chan, Cecil,Keith, Dennis D.,Wei, Chung-Chen
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p. 115 - 120
(2007/10/02)
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- USE OF MALIC ACID AS A CHIRAL SYNTHON: 24,25-DIHYDROXYCHOLECALCIFEROL
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A new chiral synthon prepared from malic acid is introduced and utilized in a synthesis of 24,25-dihydroxycholecalciferol.
- Sterling, Jeffrey,Slovin, Eliot,Barasch, Dinorah
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p. 1685 - 1688
(2007/10/02)
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