- Stereoselective synthesis of the chiral tetrahydropyrane core of swinholides and misakinolides
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Stereoselective synthesis of the optically pure tetrahydropyrane core of swinholides and misakinolide A starting from (S)-methyl lactate is described in which the highly stereoselective intramolecular iodoetherification for construction of the tetrahydropyrane ring and the regioselective ring-opening reaction of an epoxide are involved as key steps.
- Hayakawa, Hiroyuki,Iida, Kouki,Miyazawa, Masahiro,Miyashita, Masaaki
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Read Online
- Catalytic Macrocyclization Strategies Using Continuous Flow: Formal Total Synthesis of Ivorenolide A
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A formal total synthesis of ivorenolide A has been accomplished employing a Z-selective olefin cross metathesis and a macrocyclic Glaser-Hay coupling as key steps. The macrocyclization protocol employed a phase separation/continuous flow manifold whose ad
- De Léséleuc, Mylène,Godin, éric,Parisien-Collette, Shawn,Lévesque, Alexandre,Collins, Shawn K.
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Read Online
- 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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- Pyrimidine-4 (3H)-ketone heterocyclic compound, preparation method thereof and application of pyrimidine-4 (3H)-ketone heterocyclic compound in medicine
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The invention relates to pyrimidine-4 (3H)-ketone heterocyclic compounds suitable for inhibiting or regulating SHP2, a preparation method of the pyrimidine-4 (3H)-ketone heterocyclic compounds and application of the pyrimidine-4 (3H)-ketone heterocyclic compounds in medicine. Specifically, the invention relates to a compound as shown in a general formula (I) and a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof, a method for treating and/or preventing related diseases mediated by SHP2, especially cancers by using the compound or the pharmaceutically acceptable salt thereof, and a preparation method of the compound or the pharmaceutically acceptable salt thereof. The invention also relates to application of the compound or the pharmaceutically acceptable salt thereof or a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof in preparation of drugs for treating and/or preventing SHP2-mediated related diseases. Wherein each substituent in the general formula (I) is as defined in the specification.
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Paragraph 0401-0403; 0408-0411
(2021/07/21)
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- Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders
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SHP2, a non-receptor tyrosine phosphatase, plays a pivotal role in numerous oncogenic cell-signaling cascades like RAS-ERK, PI3K-AKT and JAK-STAT. On the other hand, proteolysis targeting chimera (PROTAC) has emerged as a promising strategy for the degrad
- Yang, Xiangbo,Wang, Zhijia,Pei, Yuan,Song, Ning,Xu, Lei,Feng, Bo,Wang, Hanlin,Luo, Xiaomin,Hu, Xiaobei,Qiu, Xiaohui,Feng, Huijin,Yang, Yaxi,Zhou, Yubo,Li, Jia,Zhou, Bing
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- Structure–activity relationship study of the anti-obesity natural product yoshinone A
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Yoshinone A was derived from marine algae and shown to inhibit adipogenic differentiation. The natural compound is composed of a γ-pyrone ring and a side chain and that contains two asymmetric carbons. Although their absolute configuration has been determ
- Kawazoe, Yoshinori,Itakura, Yuki,Inuzuka, Toshiyasu,Omura, Sachikazu,Uemura, Daisuke
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p. 226 - 232
(2021/03/06)
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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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- 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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- 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 0380; 0383-0385; 0889-0890
(2021/02/26)
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- PROCESS OF MANUFACTURE OF A COMPOUND FOR INHIBITING THE ACTIVITY OF SHP2
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The invention relates to a method for the manufacture of a compound of Formula I as mentioned above, or a pharmaceutically acceptable salt, acid co-crystal, hydrate or other solvate thereof, said method comprising reacting a compound of the formula II wit
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- C11-CYCLIC SUBSTITUTED 13-MEMBERED MACROLIDES AND USES THEREOF
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Provided are 13-membered macrolides for the treatment of infectious diseases. The 13- membered macrolides described herein are azaketolides. Also provided are methods for preparing the 13-membered macrolides, pharmaceutical compositions comprising the 13-
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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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- 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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- 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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- 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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- Kinetic Resolution of Racemic Aldehydes through Asymmetric Allenoate γ-Addition: Synthesis of (+)-Xylogiblactone A
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A synthesis of (+)-xylogiblactone A has been achieved from t-butyl 2-methylbuta-2,3-dienoate in a linear three-step sequence. The key elements of the synthesis include a kinetic resolution of racemic 2-silyoxyaldehyde through the allenoate γ-addition to y
- Park, Saehansaem,Pak, Gyungah,Oh, Changhwa,Lee, Jieun,Kim, Jimin,Yu, Chan-Mo
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supporting information
p. 7660 - 7664
(2019/10/02)
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- Rapid de Novo Preparation of 2,6-Dideoxy Sugar Libraries through Gold-Catalyzed Homopropargyl Orthoester Cyclization
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A flexible de novo route capable of producing libraries of 2,6-dideoxy sugars is described. We have found that Au(JackiePhos)SbF6MeCN promotes the conversion of homopropargyl orthoesters into functionalized 2,3-dihydro-4H-pyran-4-ones in good t
- Yalamanchili, Subbarao,Miller, William,Chen, Xizhao,Bennett, Clay S.
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supporting information
p. 9646 - 9651
(2019/12/02)
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- Total Synthesis and Structure Revision of Diplobifuranylone B
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An asymmetric total synthesis of diplobifuranylone B was achieved in 10 steps for the longest linear sequence and in 15.8% overall yield from commercially available methyl (R)-(+)-lactate and l-glutamic acid. This synthesis features a stereoselective construction of the key 2,5-dihydrofuran ring in the natural product via a recently developed asymmetric gold catalysis. The stereochemical flexibility offered by the catalysis enables an expedient revision of the reported structure of diplobifuranylone B, where the relative stereochemistry of the 2,5-dihydrofuran moiety was previously misassigned as cis instead of trans.
- Cheng, Xinpeng,Quintanilla, Carlos D.,Zhang, Liming
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p. 11054 - 11060
(2019/09/12)
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- Stereoselective Total Synthesis of (+)-Aristolactam GI
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Aristolactams are an important subgroup of aporphinoids, which all share a common phenanthrene chromophore motif that is thought to be responsible for the range of interesting physicochemical and biological properties exhibited by these compounds. Among all of the aristolactams discovered, (+)-aristolactam GI displays a unique structural feature of having the aristolactam scaffold linked via a benzodioxane ring to a phenyl propanoid unit, resulting in the compound being an aporphinoid-lignan hybrid. The synthesis of (+)-aristolactam GI was achieved first by synthesis of an orthogonally protected aristolactam, which was prepared using a Suzuki/aldol cascade to convert a differentially protected isoindolin-1-one to the required phenanthrene. The required enantiopure phenyl propanoid unit was prepared from readily available (R)-methyl lactate. A selective Mitsunobu reaction was used to combine these two key fragments, prior to the formation of the linking benzodioxane in the final step. The absolute stereochemistry of the natural product was confirmed to be 7′S, 8′S.
- Luong, Tuan M.,Pilkington, Lisa I.,Barker, David
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p. 5747 - 5756
(2019/05/10)
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- Stereoselective Access to (E)-1,3-Enynes through Pd/Cu-Catalyzed Alkyne Hydrocarbation of Allenes
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PdII and CuI cooperate in catalyzing the alkynes hydrocarbation of allenes (AHA) giving (E)-1,3-enynes with high yields, atom economy, and high regio-/stereoselectivities. We devised new efficient conditions and expanded the substrat
- Jeanne-Julien, Louis,Masson, Guillaume,Kouoi, Remy,Regazzetti, Anne,Genta-Jouve, Grégory,Gandon, Vincent,Roulland, Emmanuel
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supporting information
(2019/05/08)
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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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p. 3413 - 3420
(2019/05/16)
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- Synthesis of β-hydroxy-α,α-disubstituted amino acids through the orthoamide-type overman rearrangement of an α,β-unsaturated ester and stereodivergent intramolecular SN2′ reaction: Development and application to the total synthesis of sphingofungin F
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The development of a two-step synthesis for β-hydroxy-α,α- disubstituted amino acid derivatives from cyclic orthoamide is reported. The first step is the orthoamide-type Overman rearrangement of an α,β-unsaturated ester to give a sterically hindered α,α-disubstituted amidoester. The α,β-unsaturated ester is known to be a challenging substrate in the conventional Overman rearrangement due to the competitive aza-Michael reaction. However, suppression of the aza-Michael reaction is realized by two factors; 1) the high reaction temperature, and 2) an alkyl substituent at the α-position. The second step is stereodivergent intramolecular SN2′ reaction for the installation of a hydroxy group at the β-position. Either syn- or anti-type SN2′ reaction is possible by simply changing the reaction conditions. The developed method can provide all four possible stereoisomers of the β-hydroxy-α,α-disubstituted amino acid, and is successfully applied to the total synthesis of sphingofungin F.
- Sugai, Tomoya,Usui, Shunme,Tsuzaki, Shun,Oishi, Hiroki,Yasushima, Daichi,Hisada, Shoko,Fukuyasu, Takahiro,Oishi, Takeshi,Sato, Takaaki,Chida, Noritaka
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supporting information
p. 594 - 607
(2018/04/20)
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- Chiron approach towards optically pure γ-valerolactone from alanine
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A concise synthesis of both enantiomers of γ-valerolactone has been developed from commercially available Alanine. The key steps in the synthesis of these γ-Lactones are DIBAL-H reduction of ester (9) followed by in situ Wittig reaction with EtO2CCH = PPh3 ylide (13) (Z/E = 1: 3.5) and one pot lactonization triggered by deprotection of O-TBS ether (14).
- Datrika, Rajender,Kallam, Srinivasa Reddy,Katta, Rambabu,Siddaiah, Vidavalur,Pratap
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supporting information
p. 2801 - 2808
(2018/12/04)
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- Studies towards the synthesis of trocheliophorolides
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Total synthesis of trocheliophorolide C epimer is reported. The synthetic strategy involves generation of lactone skeleton and preparation of unsaturated side chain followed by cross-metathesis. The Eglinton oxidative coupling, Cadiot-Chodkiewicz cross-coupling and cross-metathesis are the key reactions used in the synthesis. We also attempted the synthesis of trocheliophorolide D epimer, which includes Cu catalyzed various cross-coupling reactions.
- Khomane, Navnath B.,Meshram, Harshadas M.,Rode, Haridas B.
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supporting information
p. 2157 - 2160
(2018/05/05)
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- 2,5-DISUBSTITUTED 3-METHYL PYRAZINES AND 2,5,6-TRISUBSTITUTED 3-METHYL PYRAZINES AS ALLOSTERIC SHP2 INHIBITORS
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The present disclosure is directed to inhibitors of SHP2 and their use in the treatment of disease. Also disclosed are pharmaceutical compositions comprising the same.
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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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- 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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p. 7679 - 7683
(2018/12/11)
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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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p. 3133 - 3138
(2018/12/04)
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- Catalyst-Controlled Multicomponent Aziridination of Chiral Aldehydes
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A highly diastereoselective and enantioselective method for the multicomponent aziridination of chiral aldehydes has been developed with BOROX catalysts of the VANOL (3,3′-diphenyl-2,2′-bi-1-naphthol) and VAPOL (2,2′-diphenyl-(4-biphenanthrol)) ligands. Very high to perfect catalyst control is observed with most all substrates examined including aldehydes with chiral centers in the α- and β-positions. High catalyst control was also observed for a number of chiral heterocyclic aldehydes allowing for the preparation of epoxy aziridines, bis(aziridines) and ethylene diaziridines. Application of this reaction in the synthesis of β3-homo-d-alloisoleucine and β3-homo-l-isoleucine is reported.
- Mukherjee, Munmun,Zhou, Yubai,Dai, Yijing,Gupta, AniL K.,Pulgam, V. Reddy,Staples, Richard J.,Wulff, William D.
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supporting information
p. 2552 - 2556
(2017/03/06)
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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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p. 6443 - 6447
(2017/10/09)
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- SYNTHESIS OF DESOSAMINES
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The present invention provides desosamine and mycaminose analogs and nitro sugars and methods for their preparation. The invention also provides methods of cyclizing a compound of Formula (Α') with glyoxal to give a nitro sugar of Formula (B). Methods for the preparation of compound of Formula (D') are provided comprising cyclization of a nitro alcohol to give a nitro sugar and reduction and alkylation of the nitro sugar to give a desosamine, mycaminose, or an analog thereof.
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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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p. 9629 - 9638
(2016/10/22)
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- Total synthesis of sphingofungin f by orthoamide-type Overman rearrangement of an unsaturated ester
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The total synthesis of sphingofungin F through the Overman rearrangement of an unsaturated ester, which is known to be an unsuitable substrate under standard conditions due to the competitive aza-Michael reaction, is described. The developed conditions enabled the ester to be compatible with the original Overman rearrangement, providing quick access to α,α-disubstituted amino acids by minimizing extra protecting group manipulations and redox reactions.
- Tsuzaki, Shun,Usui, Shunme,Oishi, Hiroki,Yasushima, Daichi,Fukuyasu, Takahiro,Oishi, Takeshi,Sato, Takaaki,Chida, Noritaka
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supporting information
p. 1704 - 1707
(2015/04/14)
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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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p. 9050 - 9054
(2015/09/01)
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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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p. 979 - 981
(2015/03/30)
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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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p. 1807 - 1817
(2015/02/19)
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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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p. 928 - 934
(2015/08/24)
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- Synthesis of β- And γ-hydroxy α-amino acids via enzymatic kinetic resolution and cyanate-to-isocyanate rearrangement
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A new strategy for stereoselective preparation of all four isomers of β- and γ-hydroxy α-amino acids is presented. The developed procedure is based on enzymatic kinetic resolution and cyanate-to-isocyanate rearrangement as key steps. Stereocontrol is achieved by proper choice of the starting hydroxyacid, the course of kinetic resolution, and the stereospecific sigmatropic rearrangement step, which proceeds with full chirality transfer.
- Szczesniak, Piotr,Padzierniok-Holewa, Agnieszka,Klimczak, Urszula,Stecko, Sebastian
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p. 11700 - 11713
(2015/02/19)
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- An organotrifluoroborate-based convergent total synthesis of the potent cancer cell growth inhibitory depsipeptides kitastatin and respirantin
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The total syntheses of the highly cytotoxic neo-antimycin macrocyclic depsipeptide natural products kitastatin and respirantin have been accomplished in a convergent manner using MNBA promoted esterifications and an efficient C- and N-terminus bis-deprote
- Beveridge, Ramsay E.,Batey, Robert A.
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supporting information
p. 2322 - 2325
(2014/05/20)
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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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- 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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- 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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p. 13618 - 13621
(2015/02/05)
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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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- 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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- Synthesis of azepino[4,5- b ]indolones by an intramolecular cyclization of unsaturated tryptamides
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A facile general route for the synthesis of azepino[4,5-b]indolones is presented. The strategy involves a Bronsted acid assisted intramolecular cyclization of unsaturated tryptamides. The methodology developed has been applied to the synthesis of the ABCD
- Nidhiry, John Eugene,Prasad, Kavirayani R.
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supporting information
p. 2585 - 2590
(2015/01/09)
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- Total synthesis of sedum alkaloids via catalyst controlled aza-cope rearrangement and hydroformylation with formaldehyde
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The catalytic asymmetric aminoallylation of chiral aldehydes is developed as a new method for the catalyst controlled synthesis of syn-and anti-1,3-aminoalcohols. This methodology is highlighted in the synthesis of the sedum alkaloids (+)-sedridine and (+)-allosedridine both of which have their final carbon incorporated during closure of the piperidine ring via a hydroformylation with formaldehyde.
- Ren, Hong,Wulff, William D.
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supporting information
p. 242 - 245
(2013/03/28)
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- Asymmetric total syntheses of (-)-penicipyrone and (-)-tenuipyrone via biomimetic cascade intermolecular michael addition/cycloketalization
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The first total syntheses of (-)-penicipyrone and (-)-tenuipyrone were accomplished enantioselectively in 12 steps with an 11% yield and 6 steps with a 28% yield from the known 4-((tert-butyldimethylsilyl)oxy)-cyclopent-2-enone, respectively, by developing a biomimetic bimolecular cascade cyclization featuring an intermolecular Michael addition/cyclo-(spiro-)ketalization sequence. The relative, absolute stereochemistry and carbon connectivity of penicipyrone was further confirmed by X-ray crystallographic analysis and comparison of optical rotations.
- Song, Liyan,Yao, Hongliang,Zhu, Liangyu,Tong, Rongbiao
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supporting information
p. 6 - 9
(2013/03/28)
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- Synthesis of a C1-C11 fragment of Zincophorin using planar chiral, neutral π-allyl iron complexes
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A key step in the synthesis of a C1-C11 fragment of the ionophore antibiotic Zincophorin involves the addition of an α-alkoxyalkylcopper(i) reagent to a planar chiral, neutral π-allyl iron complex. The key allylic alkylation reaction is highly regio- and
- Cooksey, John P.
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p. 5117 - 5126
(2013/08/23)
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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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- 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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p. 7301 - 7317
(2013/10/22)
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