- Synthesis of aplyolide A, ichthyotoxic macrolide isolated from the skin of the marine mollusk Aplysia depilans
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A convergent pathway is described for the synthesis of (S)-aplyolide A (1) using ethyl (S)-lactate as chiral source. Key steps of the synthesis are two couplings between copper(I) alkynides and propargylic halides for the formation of skipped diyne systems and were performed with an improved procedure based on the use of cesium carbonate as base for alkynide preparation.
- Spinella,Caruso,Martino,Sessa
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- New Acyclic Approach to 3-Amino-2,3,6-trideoxy-L-hexoses: a Stereocontrolled Synthesis of N-Benzoyl L-Daunosamine
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N-Benzoyl L-daunosamine was synthesized stereoselectively starting from O-t-butyldimethylsilyl L-lactaldehyde and methyl propiolate; the crucial step, intramolecular conjugate addition of a carbamoyl amino group of methyl threo-5-carbamoyloxy-4-triethylsi
- Hirama, Masahiro,Nishizaki, Itaru,Shigemoto, Takeo,Ito, Sho
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- Ultrashort helix pitch antiferroelectric liquid crystals based on chiral esters of terphenyldicarboxylic acid
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Antiferroelectric liquid crystals (AFLCs) with a nanoscale helix pitch (100 nm) were revealed in a composition containing achiral smectic-C biphenylpyrimidines and two non-mesogenic chiral dopants: p-terphenyldicarboxylates of chiral (2S)-1,1,1-trifluorooctane-2-ol and (S,S)-1,1,1-trifluorooctan-2-yl 2-hydroxypropanoate. The prepared multicomponent AFLCs exhibit two electro-optical effects, which are interrelated with the chemical structures of the mixture's components. The first effect is hysteresis free under special voltage waveform U-shaped switching, which exhibits an electro-optical response similar to that of nematic liquid crystals (NLCs) but around 1-2 orders of magnitude faster. Secondly, the deformed helix antiferroelectric liquid crystal (DHAFLC) effect has been investigated. The observed temperature independence of the electro-optical parameters, in a certain temperature range, combined with a fast U-shape response or with DHAFLC, adds a great value for applications.
- Pozhidaev,Vashchenko,Mikhailenko,Krivoshey,Barbashov,Shi,Srivastava,Chigrinov,Kwok
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- Enzymatic resolution of diethyl (3-hydroxy-1-butenyl) phosphonate
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The enzymatic esterification of diethyl (3-hydroxy-1-butenyl) phosphonate 1 with different enzymes has been carried out, and allows the preparation of (S)-1 and (R)-diethyl (3-acetoxy-1-butenyl) phosphonate 2 with very high enantiomeric excess. The absolute conguration of 1 was determined by independent synthesis from (S)-ethyl lactate.
- Attolini, Mireille,Iacazio, Gilles,Peiffer, Gilbert,Maffei, Michel
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- Total synthesis of ivorenolide a following a base-induced elimination protocol
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A concise and stereocontrolled first total synthesis of Ivorenolide A (1) is reported in 16 longest linear steps with a 13.4% overall yield starting from (+)-diethyl tartrate (DET). Key features are base-induced elimination protocol for the construction of chiral propargyl alcohols in both fragments, Pd-catalyzed cross-coupling of terminal acetylenes, and Shiina's 2-methyl-6-nitrobezoic anhydride (MNBA) mediated macrolactonization.
- Mohapatra, Debendra K.,Umamaheshwar, Gonela,Rao, R. Nageshwar,Rao, T. Srinivasa,R, Sudheer Kumar,Yadav, Jhillu S.
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- Synergistic substrate and catalyst effects in the addition of trimethylsilyl cyanide to imines derived from lactic acid
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Trimethylsilylcyanide was added to various imines derived from (2S)-ethyl lactate in the presence of Lewis acids to provide both syn- and anti- β-hydroxy-α-aminonitrile stereoisomers. Syn-products were found to be the major in most instances, however, ant
- Fields, Alexander M.,Jones, Simon
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- Total synthesis of cytotoxic pyranone B
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The first stereoselective total synthesis of cytotoxic diacetylene pyranone B is described. The key steps involved in the synthesis are base-induced elimination protocol to generate the chiral acetylenic alcohol and selective cross-coupling of unsymmetrical terminal acetylenes.
- Maheshwar Gonela, Uma,Kanikarapu, Suresh,Yadav, Jhillu S.
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- Chemoenzymatic one-pot synthesis of γ-butyrolactones
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The synthesis of enantio- and diastereomerically pure γ- butyrolactones is described using a one-pot, two-enzyme cascade. Ethyl 2-methyl-4-oxopent-2-enoate (2) was reduced selectively first in a 1,4-reduction using the old yellow enzyme (OYE1) [EC 1.6.99.1] and consecutively in a 1,2-reduction by an alcohol dehydrogenase [EC 1.1.1.2]. Copyright
- Korpak, Margarete,Pietruszka, Joerg
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- Synthesis of Methyl l -Kijanosides by Regio- And Stereoselective Ring Opening of 2-Oxazolidinone -Fused Aziridines
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Kijanose is one of the most highly functionalized deoxysugars found in nature and a challenging synthetic target. We found that the ring opening of trisubstituted, 2-oxazolidinone-fused aziridines is regio- and stereoselective, and the azide adduct has the same stereochemistry as that of kijanose after converting the azido to a nitro group. Therefore, both α- and β-methyl l-kijanosides were prepared from ethyl l-lactate in 14% total yield.
- Angamuthu, Venkatachalam,Chen, Wei-Chen,Hou, Duen-Ren,Liu, Chi-Yun
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- Pd-catalyzed asymmetric intermolecular hydroalkoxylation of allene: An entry to cyclic acetals with activating group-free and flexible anomeric control
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A ligand-directed metal-catalyzed asymmetric intermolecular hydroalkoxylation of alkoxyallene is reported. Combined with ring-closing-metathesis, this reaction offers a new atom-efficient synthetic method toward various cyclic acetals with elaborate anomeric control. Synthetic utility of the reaction was demonstrated by the atom-efficient and stereodivergent access to various mono- and disaccharides.
- Lim, Wontaeck,Kim, Jungjoon,Rhee, Young Ho
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- Hydrosulfonylation Reaction with Arenesulfonyl Chlorides and Tetrahydrofuran: Conversion of Terminal Alkynes into Cyclopentylmethyl Sulfones
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An efficient and simple radical chain reaction to convert terminal alkynes into arenesulfonylmethylcyclopentanes is described. The reaction involves a radical addition–translocation–cyclization process and necessitates solely the use of readily available arenesulfonyl chlorides in tetrahydrofuran. Interestingly, this radical-mediated C?H activation process took place with a high level of retention of configuration when an enantiomerically pure starting material was used.
- Gloor, Christian Simon,Dénès, Fabrice,Renaud, Philippe
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- Studies toward the Total Synthesis of the Marine Macrolide Salarin C
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A convergent strategy for the synthesis of dideoxysalarin C (3) as a potential intermediate for the total synthesis of the marine macrolide salarin C (1) is described. The macrolactone core of 3 was assembled by Suzuki coupling between alkyl iodide 9 and
- Schrof, Raffael,Altmann, Karl-Heinz
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- Total synthesis of synargentolide B
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A simple and efficient stereoselective synthesis of synargentolide B was achieved by using ethyl (S)-2-hydroxypropanoate as a readily available starting material. The key steps involved in the synthesis are Horner-Wadsworth-Emmons olefination, Sharpless a
- Ramulu, Udugu,Rajaram, Singanaboina,Ramesh, Dasari,Suresh Babu, Katragadda
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- A facile approach for the synthesis of C13-C24 fragments of maltepolides A, C and D
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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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- Chiron approach for the total synthesis of (+)-synargentolide B
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A concise and efficient chiron approach for the total synthesis of natural product synargentolide B was achieved in 10 steps with overall yields of 11.3% from D-mannitol and L-ethyl lactate. The key reactions included anti-Barbier allylation, cross-metathesis, and an intramolecular Yamaguchi esterification.
- Liu, Jun,Gao, Yangguang,Wang, Linlin,Du, Yuguo
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- PYRAZOLO[3,4-B]PYRAZINE SHP2 PHOSPHATASE INHIBITORS
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The invention provides new pyrazine derivatives of formula (I): or a tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein. The invention also provides pharmaceutical compositions comprising sa
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Page/Page column 127
(2021/02/26)
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- SHP2 INHIBITORS AND USES THEREOF
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Compounds of Formula 1 as inhibitors of protein tyrosine phosphatase SHP2 are disclosed. The pharmaceutical compositions comprising compounds of Formula 1, methods of synthesis of these compounds, methods of treatment for diseases associated with the aberrant activity of SHP2 such as cancer using these compounds or compositions containing these compounds are also disclosed.
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Page/Page column 133; 134
(2021/04/02)
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- A Unified Strategy for the Asymmetric Synthesis of Highly Substituted 1,2-Amino Alcohols Leading to Highly Substituted Bisoxazoline Ligands
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A general procedure for the asymmetric synthesis of highly substituted 1,2-amino alcohols in high yield and diastereoselectivity is described that uses organometallic additions of a wide range of nucleophiles to tert-butylsulfinimines as the key step. The addition of organolithium reagents to these imines follows a modified Davis model. The diastereoselectivity for this reaction depends significantly on both the nucleophile and electrophile. These highly substituted 1,2-amino alcohols are used to synthesize stereochemically diverse and structurally novel, polysubstituted 2,2′-methylene(bisoxazoline) ligands in high yields.
- Shrestha, Bijay,Rose, Brennan T.,Olen, Casey L.,Roth, Aaron,Kwong, Adon C.,Wang, Yang,Denmark, Scott E.
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p. 3490 - 3534
(2021/02/16)
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- PYRIMIDINE-FUSED CYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
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Disclosed in the present disclosure are a pyrimidine-fused cyclic compound or a pharmaceutically acceptable salt, hydrate, prodrug, stereoisomer, solvate or isotope labeled compound thereof. Also provided in the present disclosure are a preparation method for the compound, a composition comprising the compound and a use of the compound for the preparation of a medicament for the prevention and/or treatment of a disease or condition associated with abnormal SHP2 activity.
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Paragraph 0313; 0380-0382; 0886-0888
(2021/02/26)
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- HETEROBICYCLIC COMPOUNDS FOR INHIBITING THE ACTIVITY OF SHP2
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A compound of formula (I):wherein Ring A, Q, R1,R2, R3, R4, R5, R6, R7, R8, R9, R10, R11,X, a,b, c and d are as defined in the specification.
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Paragraph 0461; 0462
(2020/02/16)
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- IMIDAZOPYRIMIDINE DERIVATIVES
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The present disclosure provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating cancers.
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Paragraph 0837-0838
(2020/04/29)
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- METHODS AND COMPOSITIONS
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The invention relates to genetic incorporation of 2,3-diamino propionic acid (DAP) into polypeptides, to unnatural amino acids comprising DAP, to a tRNA synthetase for charging tRNA with unnatural amino acids comprising DAP, and to methods of using the resulting polypeptides, for example in capturing substrates and/or intermediates in enzymatic reactions. The invention also relates to compounds of formula (I) or (II): or salts, solvates, tautomers, isomers or mixtures thereof.
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Page/Page column 82; 84
(2020/05/29)
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- Steric Enforcement of cis-Epoxide Formation in the Radical C-O-Coupling Reaction by Which (S)-2-Hydroxypropylphosphonate Epoxidase (HppE) Produces Fosfomycin
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(S)-2-Hydroxypropylphosphonate [(S)-2-HPP, 1] epoxidase (HppE) reduces H2O2 at its nonheme-iron cofactor to install the oxirane "warhead" of the antibiotic fosfomycin. The net replacement of the C1 pro-R hydrogen of 1 by its C2 oxygen, with inversion of configuration at C1, yields the cis-epoxide of the drug [(1R,2S)-epoxypropylphosphonic acid (cis-Fos, 2)]. Here we show that HppE achieves ~95% selectivity for C1 inversion and cis-epoxide formation via steric guidance of a radical-coupling mechanism. Published structures of the HppE·FeII·1 and HppE·ZnII·2 complexes reveal distinct pockets for C3 of the substrate and product and identify four hydrophobic residues - Leu120, Leu144, Phe182, and Leu193 - close to C3 in one of the complexes. Replacement of Leu193 in the substrate C3 pocket with the bulkier Phe enhances stereoselectivity (cis:trans ~99:1), whereas the Leu120Phe substitution in the product C3 pocket diminishes it (~82:18). Retention of C1 configuration and trans-epoxide formation become predominant with the bulk-reducing Phe182Ala substitution in the substrate C3 pocket (~13:87), trifluorination of C3 (~23:77), or both (~1:99). The effect of C3 trifluorination is counteracted by the more constrained substrate C3 pockets in the Leu193Phe (~56:44) and Leu144Phe/Leu193Phe (~90:10) variants. The ability of HppE to epoxidize substrate analogues bearing halogens at C3, C1, or both is inconsistent with a published hypothesis of polar cyclization via a C1 carbocation. Rather, specific enzyme-substrate contacts drive inversion of the C1 radical - as proposed in a recent computational study - to direct formation of the more potently antibacterial cis-epoxide by radicaloid C-O coupling.
- Zhou, Shengbin,Pan, Juan,Davis, Katherine M.,Schaperdoth, Irene,Wang, Bo,Boal, Amie K.,Krebs, Carsten,Bollinger, J. Martin
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supporting information
p. 20397 - 20406
(2019/12/27)
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- TRICYCLIC HETEROARYL-SUBSTITUTED QUINOLINE AND AZAQUINOLINE COMPOUNDS AS PAR4 INHIBITORS
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Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII) or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a tricyclic heteroaryl group substituted with R3a and zero to 2 R3b; and R1, R2, R3a, R3b, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
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Page/Page column 157
(2018/03/09)
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- BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS
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Disclosed are compounds of Formula (I) to (IV): [INSERT CHEMICAL STRUCTURE HERE] or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmace
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Page/Page column 97; 98
(2018/03/09)
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- BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS
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Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
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Page/Page column 115
(2018/03/25)
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- Stereoselective total synthesis of (?)-pyrenophorol
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Abstract: A simple and efficient stereoselective synthesis of macrodilactone of (?)-pyrenophorol (1) has been accomplished in 12 steps in 8.3% overall yield, from inexpensive and commercially available (S)-ethyl lactate. This convergent synthesis utilizes an oxidation–reduction protocol and cyclodimerisation under the Mitsunobu reaction conditions as key steps.
- Ashok, Dongamanti,Pervaram, Sridhar,Chittireddy, Venkata Ramana Reddy,Reddymasu, Sreenivasulu,Vuppula, Naresh Kumar
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p. 971 - 977
(2018/03/28)
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- 1,4-THIAZINE DIOXIDE AND 1,2,4-THIADIAZINE DIOXIDE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE
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The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, X, R2, R2', R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
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Page/Page column 261-262
(2018/07/05)
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- Modifications of flexible nonyl chain and nucleobase head group of (+)-erythro-9-(2′s-hydroxy-3′s-nonyl)adenine [(+)-EHNA] as adenosine deaminase inhibitors
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A series of terminal nonyl chain and nucleobase modified analogues of (+)-EHNA (III) were synthesized and evaluated for their ability to inhibit adenosine deaminase (ADA). The constrained carbon analogues of (+)-EHNA, 7a-7h, 10a-c, 12, 13, 14 and 17a-c appeared very potent with Ki values in the low nanomolar range. Thio-analogues of (+)-EHNA 24a-e wherein 5′C of nonyl chain replaced by sulfur atom found to be less potent compared to (+)-EHNA. Docking of the representative compounds into the active site of ADA was performed to understand structure-activity relationships. Compounds 7a (Ki: 1.1 nM) 7b (Ki: 5.2 nM) and 26a (Ki: 5.9 nM) showed suitable balance of potency, microsomal stability and demonstrated better pharmacokinetic properties as compared to (+)-EHNA and therefore may have therapeutic potential for various inflammatory diseases, hypertension and cancer.
- Kandalkar, Sachin R.,Ramaiah, Parimi Atchuta,Joshi, Manoj,Wavhal, Atul,Waman, Yogesh,Raje, Amol A.,Tambe, Ashwini,Ansari, Shariq,De, Siddhartha,Palle, Venkata P.,Mookhtiar, Kasim A.,Deshpande, Anil M.,Barawkar, Dinesh A.
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p. 5799 - 5819
(2017/09/28)
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- Chiron Approaches to the Antitumor Natural Product Fuzanin D
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Fuzanin D, a pyridine-containing natural product, which exhibits cytotoxic activity against DLD-1 cells, is synthesized in a concise manner using l-arabinose or ethyl l-lactate as chiral pool substrates in nine steps (14.4% overall yield) and six steps (30.8% overall yield), respectively. The key steps involve Wittig olefination and olefin cross--metathesis.
- Gao, Yangguang,Cao, Zhou,Su, Chengzhong,Chen, Zefeng,He, Xianran,Ding, Fei,Li, Hang,Zhang, Yongmin
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p. 4471 - 4476
(2016/12/14)
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- An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: Generality, applications and mechanistic investigations
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The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.
- Richmond, Edward,Ling, Kenneth B.,Duguet, Nicolas,Manton, Lois B.,elebi-?lcüm, Nihan,Lam, Yu-Hong,Alsancak, Sezen,Slawin, Alexandra M. Z.,Houk,Smith, Andrew D.
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supporting information
p. 1807 - 1817
(2015/02/19)
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- A lactate-derived chiral aldehyde for determining the enantiopurity of enantioenriched primary amines
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In this paper we describe the use of a chiral aldehyde derived from lactate esters for determining the enantiopurity of primary amines, via the formation of diastereomeric imines. The method was shown to be suitable for reproducibly determining the enantiopurity of a diverse set of chiral amines. Both enantiomers of the aldehyde can be prepared in two steps from commercially available materials.
- Gibson, Samantha M.,Lanigan, Rachel M.,Benhamou, Laure,Aliev, Abil E.,Sheppard, Tom D.
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supporting information
p. 9050 - 9054
(2015/09/01)
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- Absolute configurations of melanoxadin, MR-93A, melanoxazal, and MR-93B
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Fungal metabolites melanoxadin, MR-93A, melanoxazal, and MR-93B were synthesized with the key stereogenic centers derived from commercially available chiral building blocks. The optically active synthetic products with well-defined absolute configurations provided authentic samples for the stereoisomers of these oxazole-containing natural products and thus allowed for unambiguous assignments of their relative and absolute configurations. The large discrepancies in the optical rotations between the natural and the pure synthetic samples are discussed. Some errors in the previously reported NMR signal assignments are also corrected.
- He, Tian-Jun,Zhu, Shijun,Lu, Xiao-Wei,Wu, Yikang,Li, Yan
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p. 647 - 654
(2015/01/30)
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- Metathesis-based de novo synthesis of noviose
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The rare carbohydrate L-(+)-noviose was synthesized from enantiomerically pure L-lactate. The configuration at C-4 was established by diastereoselective nucleophilic addition to an in-situ-generated lactaldehyde. The resulting homoallylic alcohol was further transformed into a set of ring-closing metathesis (RCM) precursors. These compounds were converted into noviose in few steps using RCM and RCM-allylic-oxidation sequences. S-Ethyl lactate was converted into an enantiomerically pure tertiary homoallylic alcohol, which was then transformed into noviose using olefin metathesis reactions. Copyright
- Schmidt, Bernd,Hauke, Sylvia
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p. 1951 - 1960
(2014/04/03)
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- SUBSTITUTED PYRIDINONE COMPOUNDS AS MEK INHIBITORS
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The invention provides novel substituted heterocyclic compounds represented by Formula I and Formula II, or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans.
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Page/Page column 39; 40
(2015/01/07)
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- Metathesis-Based de Novo Synthesis of Noviose
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The rare carbohydrate L-(+)-noviose was synthesized from enantiomerically pure L-lactate. The configuration at C-4 was established by diastereoselective nucleophilic addition to an in-situ-generated lactaldehyde. The resulting homoallylic alcohol was further transformed into a set of ring-closing metathesis (RCM) precursors. These compounds were converted into noviose in few steps using RCM and RCM-allylic-oxidation sequences.
- Schmidt, Bernd,Hauke, Sylvia
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p. 1951 - 1960
(2015/10/05)
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- 1,4-DISUBSTITUTED PYRIDAZINE ANALOGS AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 42; 43
(2014/03/22)
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- COMPOSITIONS AND METHODS FOR DIRECTING THE OPPOSITION OF MOSQUITOES
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Compositions described herein are purposed to attract gravid mosquitoes to oviposit in a preferred environment. The composition for directing the oviposition of mosquitoes comprises one or more attractants and N-P-K additive, wherein the N-P-K additive is
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- Organoboron-based allylation approach to the total synthesis of the medium-ring dilactone (+)-antimycin A1b
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The stereoselective synthesis of (+)-antimycin A1b has been accomplished in 12 linear steps and 18% overall yield from (-)-ethyl lactate. A robust, scalable, and highly diastereoselective montmorillonite K10-promoted allylation reaction between
- Janetzko, John,Batey, Robert A.
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p. 7415 - 7424
(2014/10/15)
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- Stereoselective total synthesis of 4-ketoclonostachydiol
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An efficient stereoselective total synthesis of the bioactive 14-membered natural macrocyclic bislactone 4-ketoclonostachydiol is described. The strategy involves a Jacobsen's hydrolytic kinetic resolution (HKR), epoxide opening, MacMillan α-hydroxylation, Horner-Wadsworth-Emmons olefination, a Grignard reaction, and Hoveyda-Grubbs-II-catalyzed ring-closing metathesis (RCM) as key steps.
- Rajaram, Singanaboina,Ramulu, Udugu,Ramesh, Dasari,Prabhakar, Peddikotla,Venkateswarlu, Yenamandra
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p. 2115 - 2123
(2013/12/04)
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- Total synthesis of a 6,6-spiroketal metabolite, dinemasone A
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The stereoselective total synthesis of dinemasone A has been accomplished. The key reactions, Sharpless asymmetric epoxidation, lithium-mediated epoxy alcohol opening, and double-intramolecular hetero-Michael addition, gave access to dinemasone A from lac
- Raji Reddy, Chada,Srikanth, Boinapally,Dilipkumar, Uredi,Rao, Kakita Veera Mohana,Jagadeesh, Bharatam
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p. 525 - 532
(2013/02/26)
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- Optimization of antitumor modulators of pre-mRNA splicing
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The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously, natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators that demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), HeLa (IC50 = 50 nM), and SK-N-AS (IC 50 = 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers.
- Lagisetti, Chandraiah,Palacios, Gustavo,Goronga, Tinopiwa,Freeman, Burgess,Caufield, William,Webb, Thomas R.
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supporting information
p. 10033 - 10044
(2014/01/17)
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- TAK1 KINASE INHIBITORS, COMPOSITIONS, AND USED RELATED THERETO
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The disclosure relates to TAK1 inhibitors, compositions, and uses related thereto. In certain embodiments, the disclosure relates to compounds of formula (I), pharmaceutical compositions having a compound of formula (I), and methods of treating or prevent
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Page/Page column 48; 49
(2013/03/26)
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- Metal-free, hydroacylation of CC and NN bonds via aerobic C-H activation of aldehydes, and reaction of the products thereof
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In this report, a thorough evaluation of the use of aerobically initiated, metal-free hydroacylation of various CC and NN acceptor molecules with a wide range of aldehydes is presented. The aerobic-activation conditions that have been developed are in sharp contrast to previous conditions for hydroacylation, which tend to use transition metals, peroxides that require thermal or photochemical degradation, or N-heterocyclic carbenes. The mildness of the conditions enables a number of reactions involving sensitive reaction partners and, perhaps most significantly, allows for α-functionalised chiral aldehydes to undergo radical-based hydroacylation with complete retention of optical purity. We also demonstrate how the resulting hydroacylation products can be transformed into other useful intermediates, such as γ-keto- sulfonamides, sultams, sultones, cyclic N-sulfonyl imines and amides.
- Chudasama, Vijay,Akhbar, Ahmed R.,Bahou, Karim A.,Fitzmaurice, Richard J.,Caddick, Stephen
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supporting information
p. 7301 - 7317
(2013/10/22)
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- Synthesis of undecachlorosulfolipid A: Re-evaluation of the nominal structure
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Halo-giant: The title compound at the left in the scheme was constructed by the synthesis and coupling of two stereochemically challenging fragments. A comparison of the NMR data of the synthetic material and the natural product indicates that the configuration had been misassigned in the latter. PT=5-(1-phenyltetrazolyl).
- Nilewski, Christian,Deprez, Nicholas R.,Fessard, Thomas C.,Li, Dong Bo,Geisser, Roger W.,Carreira, Erick M.
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supporting information; experimental part
p. 7940 - 7943
(2011/10/08)
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- BICYCLIC HETEROCYCLES AS MEK KINASE INHIBITORS
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The invention relates to bicyclic heterocycles of formulae I and II with anti-cancer and/or anti-inflammatory activity and more specifically with MEK kinase inhibitory activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth, treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 54
(2010/04/03)
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- NEW CAMPTOTHECIN DERIVATIVES AND USES THEREOF
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The present invention provides two new camptothecin derivatives, which were identified as S,R- and S,S-topotecan lactates, respectively. Both compounds have anticancer activities. Pharmaceutical compositions of the new camptothecin derivatives, and cancer therapies with the new camptothecin derivatives or their pharmaceutical compositions were also provided.
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Page/Page column 7
(2010/09/17)
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- Regioselective intramolecular dipolar cycloaddition of azides and unsymmetrical alkynes
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(Figure presented) Enantioenriched allenylsilanes are used in three-component propargylatlon reactions with aldehydes and silyl ethers to form syn-homopropargylic ethers that contain an imbedded azide. These materials then undergo thermally Induced intram
- Brawn, Ryan A.,Welzel, Morgan,Lowe, Jason T.,Panek, James S.
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scheme or table
p. 336 - 339
(2010/03/25)
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- The rhodium-catalyzed carbene cyclization cycloaddition cascade reaction of vinylsulfonates
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Vinylsulfonates have proved to be excellent dipolarophiles for carbonyl ylides derived from diazoketones in rhodium-catalyzed intramolecular cycloadditions. Polyfunctional substrates, such as 8 and (+)-15, were readily available from hydroxy esters, e.g. 1 and the cyclopenta-1,3-dione 10, respectively, and the resulting polycyclic sultones were formed under mild reaction conditions in high yields with very good diastereoselectivities. A ruthenium-catalyzed asymmetric transfer hydrogenation was found to desymmetrize the meso-cyclopenta-1,3-dione 12 efficiently.
- Shi, Bairu,Merten, Sandra,Wong, David K. Y.,Chu, John C. K.,Liu, Lok Lok,Lam, Sze Kui,J?ger, Anne,Wong, Wing-Tak,Chiu, Pauline,Metz, Peter
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supporting information; experimental part
p. 3128 - 3132
(2010/04/24)
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- Polyketide building blocks via diastereoselective nitrile oxide cycloadditions with homoallylic alcohols and monoprotected homoallylic diols
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A modular approach to δ2-isoxazolines, latent aldol adducts and polyketide building blocks, is reported. The magnesium-mediated, hydroxyl-directed method allows for the diastereoselective access to a wide variety of masked β-hydroxy ketones, starting from readily available aliphatic and aromatic oximes, homoallylic alcohols and monoprotected homoallylic diols. The utility of the prepared δ2-isoxazolines as polyketide building blocks is demonstrated by their ready conversion into the corresponding β-hydroxy ketones. The anti-diastereoselectivity of the reaction was established by derivatization, NOE studies and comparison of known compounds. A rationale for the observed diastereoselectivity is proposed.
- Lohse-Fraefel, Nina,Carreira, Erick M.
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supporting information; experimental part
p. 12065 - 12081
(2010/05/18)
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- The tandem ring-closing metathesis-isomerization approach to 6-deoxyglycals
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Protected 3,6-dideoxyglycals have been synthesized de novo as single isomers starting from ethyl lactate by using the tandem RCM-isomerization reaction as the key step. Different relative configurations become accessible by addition of vinyl- or allylmeta
- Schmidt, Bernd,Biernat, Anne
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experimental part
p. 6135 - 6141
(2009/06/05)
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- Ether-directed palladium(II)-catalysed aza-Claisen rearrangements: studies on the origin of the directing effect
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Four new chiral δ-substituted allylic trichloroacetimidates have been synthesised to probe the origin of the high diastereoselectivity observed for the MOM-ether directed palladium(II)-catalysed aza-Claisen rearrangement. Rearrangement of these compounds has not only provided strong evidence for this directing effect but also that during the rearrangement both oxygen atoms from the MOM-ether are involved in coordinating to and directing the palladium(II) catalyst.
- Jamieson, Andrew G.,Sutherland, Andrew
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p. 2123 - 2131
(2007/10/03)
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- Total synthesis of jerangolid D
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A short and convergent synthesis of jerangolid D is described. As key steps, a Blaise reaction is employed to construct the lactone ring, a diastereoselective multicomponent Sakurai condensation leads to the dihydropyran ring, and the skipped diene is ass
- Pospisil, Jiri,Marko, Istvan E.
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p. 3516 - 3517
(2008/01/01)
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