- METHOD FOR PREPARING ALKYL HYDROXYL ACID ESTER AND USE THEREOF
-
Provided is a method for preparing an alkyl hydroxyl acid ester, the product and use thereof. The method has advantages of high yield, not producing waste water, gas, or solid, low cost, and is green and environment friendly.
- -
-
Page/Page column 6
(2021/09/17)
-
- Preparation process of methyl glycolate
-
The preparation process comprises the following steps: firstly adding an organic solvent and glycolic acid into a three-necked flask, stirring at low temperature, adding bromide, and controlling the reaction temperature to be low temperature. The reaction
- -
-
Paragraph 0029-0055
(2021/11/03)
-
- Ni-Catalyzed C(sp3)–O Arylation of α-Hydroxy Esters
-
A Negishi cross-coupling of α-hydroxy ester derivatives and arylzinc reagents has been developed. This reaction tolerates both primary and secondary C(sp3)–O alcohol precursors and achieves efficient cross-coupling under Ni catalysis without the need for added external metal reductant, photocatalyst, or additives. The arylation of readily accessible C(sp3)–O electrophiles in this operationally simple, rapid, and mild reaction provides a complementary way of accessing desirable α-aryl ester products.
- Monteith, John J.,Rousseaux, Sophie A. L.
-
supporting information
p. 9485 - 9489
(2021/12/09)
-
- Preparation method and application of hydroxy acid alkyl ester
-
The invention relates to a preparation method of a green solvent hydroxy acid alkyl ester, which comprises the following steps: (1) an alkyl alcohol and a hydroxy acid methyl ester or an ethyl ester are mixed under normal pressure or micro-positive pressure in the presence of a catalyst and reacted at the temperature of 50-200 DEG C, and the molar ratio of alkyl alcohol to the hydroxy acid methylester or ethyl ester is greater than 1; (2) at the temperature of 135-170 DEG C, a product methanol or ethanol is fractionated for the first time, and the top temperature of a fractionating column isthe boiling point temperature of methanol or ethanol; (3) atmospheric pressure or reduced pressure distillation is carried out for the second time to obtain redundant reactants alkyl alcohol and unreacted hydroxy acid methyl ester or ethyl ester, and the distillation temperature is controlled to be the boiling point temperature of the alkyl alcohol and the hydroxy acid methyl ester or ethyl ester;and (4) the remaining product hydroxy acid alkyl ester is collected. The method has the advantages of high yield, no generation of any three wastes, low production cost, greenness and environmental protection.
- -
-
Paragraph 0031-0033
(2020/06/16)
-
- Fluorinated taxane compound, preparation method therefor and application of fluorinated taxane compound
-
The invention discloses a fluorinated taxane compound, a preparation method therefor and an application of the fluorinated taxane compound. The compound has a structural general formula represented bya formula I. Proven by pharmacological experiments, compared with paclitaxel, a series of fluorinated taxane derivatives synthesized by the method have cytotoxicity superior to that of the paclitaxelto a multidrug-resistant human mammary cancer cell line MCF-7/Adr and an ovarian cancer cell line NCI/Adr and represent cytotoxicity superior to that of the paclitaxel to a colon cancer cell line HCT-116 with overexpressed neoplasm stem cells.
- -
-
Paragraph 0048-0054
(2019/08/30)
-
- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BROMODOMAIN-CONTAINING PROTEINS
-
The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.
- -
-
Paragraph 00286
(2017/03/21)
-
- TAXANE COMPOUND, AND PREPARATION METHOD AND USE THEREOF
-
Provided are taxanes compounds having the structure of formula I, preparation method thereof, and uses of compositions having the compound, pharmaceutical salts and solvates thereof as active ingredients in the preparation of oral antitumor drugs. In the formula, R1 is —COR6, —COOR6, and —CONR7aR7b; R2 is C1-C6 alkyl, C1-C6 alkenyl group, a substituted hydrocarbon group, a heterocyclic group, an aromatic group or a substituted aromatic group; R3 is —OR6, —OCOOR6, —OCOSR6, and —OCONR7aR7b; R4 is —OR6, —OCOOR6, —OCOSR6, —OCONR7aR7b, H, and OH; R6 is C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl group, a substituted hydrocarbon group, an aromatic group or a heterocyclic group; and R7a and R7b are respectively hydrogen, a hydrocarbon group, a substituted hydrocarbon group or a heterocyclic group.
- -
-
Paragraph 0126; 0127
(2016/12/16)
-
- Taxanes Compounds, Preparation Method Therefor, and Uses Thereof
-
The present invention provides taxanes compounds with a formula (I) or formula (II) structure, a method for preparing the compounds, as well as the use of the compositions containing the compounds, pharmaceutically acceptable salts and solvates thereof as active ingredients in manufacturing oral antitumor medicaments, In formula (I), R1 is —COR6, —COOR6 or —CONR7aR7b; R2 is a C1-C6 alkyl, a C1-C6 alkenyl, a substituted hydrocarbon group, a heterocyclic group, an aromatic group or a substituted aromatic group; R3 is —OR6, —OCOOR6, —OCOSR6 or —OCONR7aR7b; R4 is —OR6, —OCOOR6, —OCOSR6, —OCONR7aR7b or H; wherein, R6 is a C1-C6 alkyl, a C1-C6 alkenyl, a C1-C6 alkynyl, a substituted hydrocarbon group, an aromatic group or a heterocyclic group; R7a and R7b are respectively hydrogen, a hydrocarbon group, a substituted hydrocarbon group or a heterocyclic group. In formula (II), R1 is —COR6 or —COOR6; R2 is an aromatic group; R3 is —OR6; wherein, R6 is a C1-C6 alkyl, a C1-C6 alkenyl, a C1-C6 alkynyl, a substituted hydrocarbon group, an aromatic group or a heterocyclic group.
- -
-
Paragraph 0150; 0151
(2016/10/31)
-
- Design, synthesis, and biological characterization of tamibarotene analogs as anticancer agents
-
In our efforts of developing novel compounds as potential anticancer agents, a series of tamibarotene analogs containing Zn2+-binding moieties were designed and developed. Biological characterization identified compound 7b as the most potent one with improved antiproliferative activities against multiple cancer cell lines, compared to parent compound tamibarotene. Further characterization also demonstrated that compound 7b exhibited moderate activities as a histone deacetylase inhibitor with IC50 of 1.8?±?0.1?μm, thus suggesting that this could contribute to the improved antiproliferative activities of 7b. Pharmacokinetic studies revealed that compound 7b could release tamibarotene after administration and prolong the circulation time of tamibarotene, and this may also potentially contribute to the improved antiproliferative activities. Collectively, the results demonstrated that compound 7b could serve as a new lead for further development of more potent analogs as potential anticancer agents.
- Jiang, Yuqi,Li, Xiaoyang,Wang, Xue,Wang, Zhonglan,Zhang, Jian,Wu, Jingde,Xu, Wenfang
-
p. 542 - 555
(2016/10/06)
-
- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
-
The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
- -
-
Paragraph 0714
(2013/04/10)
-
- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
-
The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
- -
-
Page/Page column 134
(2013/04/13)
-
- Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
-
VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on β-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX.
- Jia, Chao,Yang, Ke-Wu,Liu, Cheng-Cheng,Feng, Lei,Xiao, Jian-Min,Zhou, Li-Sheng,Zhang, Yi-Lin
-
supporting information; experimental part
p. 482 - 484
(2012/03/11)
-
- NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold
-
Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 ca
- Zall, Andrea,Kieser, Daniel,Hoettecke, Nicole,Naumann, Eva C.,Thomaszewski, Binia,Schneider, Katrin,Steinbacher, Dirk T.,Schubenel, Robert,Masur, Stefan,Baumann, Karlheinz,Schmidt, Boris
-
supporting information; experimental part
p. 4903 - 4909
(2011/10/04)
-
- OEI800 polyconjugates linked with ketalized glycolic acid for use as gene vectors
-
Endosomal escape of DNA polyplexes is one prominent bottleneck involved in the transfection process. Purposely against the low pH level in the endosome compartment, a series of acid-cleavable gene vectors constructed from oligoethyleneimine OEI800 polycon
- Luo, Xiao-Hua,Liu, Chen-Wei,Li, Ze-Yong,Qin, Si-Yong,Feng, Jun,Zhang, Xian-Zheng,Zhuo, Ren-Xi
-
experimental part
p. 15305 - 15315
(2012/02/02)
-
- New insights into poly(lactic- co -glycolic acid) microstructure: Using repeating sequence copolymers to decipher complex NMR and thermal behavior
-
Sequence, which Nature uses to spectacular advantage, has not been fully exploited in synthetic copolymers. To investigate the effect of sequence and stereosequence on the physical properties of copolymers, a family of complex isotactic, syndiotactic, and atactic repeating sequence poly(lactic-co-glycolic acid) copolymers (RSC PLGAs) were prepared and their NMR and thermal behavior was studied. The unique suitability of polymers prepared from the bioassimilable lactic and glycolic acid monomers for biomedical applications makes them ideal candidates for this type of sequence engineering. Polymers with repeating units of LG, GLG and LLG (L = lactic, G = glycolic) with controlled and varied tacticities were synthesized by assembly of sequence-specific, stereopure dimeric, trimeric, and hexameric segmer units. Specifically labeled deuterated lactic and glycolic acid segmers were likewise prepared and polymerized. Molecular weights for the copolymers were in the range Mn = 12-40 kDa by size exclusion chromatography in THF. Although the effects of sequence-influenced solution conformation were visible in all resonances of the 1H and 13C NMR spectra, the diastereotopic methylene resonances in the 1H NMR (CDCl3) for the glycolic units of the copolymers proved most sensitive. An octad level of resolution, which corresponds to an astounding 31-atom distance between the most separated stereocenters, was observed in some mixed sequence polymers. Importantly, the level of sensitivity of a particular NMR resonance to small differences in sequence was found to depend on the sequence itself. Thermal properties were also correlated with sequence.
- Stayshich, Ryan M.,Meyer, Tara Y.
-
supporting information; experimental part
p. 10920 - 10934
(2010/09/17)
-
- Nanoscale ionic diodes with tunable and switchable rectifying behavior
-
(Figure Presented) Nanoscale ionic diodes have attracted interest as circuit elements for development of nanofluidic devices for a variety of applications, including biosensing, constructing artificial cells, and engineering biological batteries. This paper presents a bottom-up, self-assembly approach for constructing nanopores with rectified conductance behavior in a membrane using semisynthetic derivatives of the ion-channel-forming peptide gramicidin A. The capability to individually access each half of a dimeric gramicidin channel makes it possible to generate asymmetric channels in a membrane that exhibit diodelike conductance properties. The modular nature of these self-assembled channels affords the possibility of tuning their rectifying conductance properties by simple replacement of one peptide derivative with another in the membrane. Additionally, introduction of an external stimulus (here, an enzyme) to change the functional group attached to one side of the gramicidin pore induces diodelike conductance behavior in previously nonrectified channels, demonstrating the possibility of switching the conductance properties of these nanopores in situ in a controlled manner. Copyright
- Macrae, Michael X.,Blake, Steven,Mayer, Michael,Yang, Jerry
-
supporting information; experimental part
p. 1766 - 1767
(2010/04/25)
-
- Synthesis of substrates for the characterisation of sialate-O- acetyltransferases
-
The synthesis of a series of α-and β-configured sialosides using a Koenigs-Knorr methodology is described. The target compounds can serve as substrates for the investigation of biologically relevant sialate-O- acetyltransferase activity.
- Eleuterio, Ines,Streicher, Hansjoerg
-
experimental part
p. 562 - 564
(2011/02/25)
-
- Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats
-
The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.
- Gynther, Mikko,Ropponen, Jarmo,Laine, Krista,Lepp?nen, Jukka,Haapakoski, Paula,Peura, Lauri,J?rvinen, Tomi,Rautio, Jarkko
-
supporting information; experimental part
p. 3348 - 3353
(2010/03/05)
-
- Evaluation of nitrate-substituted pseudocholine esters of aspirin as potential nitro-aspirins
-
Herein we explore some designs for nitro-aspirins, compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t1/2 ～ 1 min) but generating exclusively the corresponding nitro-salicylate. The one exception, an N-propyl, N-nitroxyethyl aminoethanol ester produced 9.2% aspirin in molar terms indicating that the nitro-aspirin objective is probably achievable if due cognisance can be paid to the demands of the activating enzyme. Even at this low level of aspirin release, this compound is the most successful nitro-aspirin reported to date in the key human plasma model.
- Gilmer, John F.,Moriarty, Louise M.,Clancy, John M.
-
p. 3217 - 3220
(2008/02/05)
-
- Synthesis and in vitro enzyme hydrolysis of trioxadiaza- and tetraoxadiaza-crown ether-based complexing agents with disposable ester pendant arms
-
New disposable ester derivatives of the complexing agents N,N′-bis(carboxymethyl)piperazine, -homopiperazine, -1,7-diaza-15-crown-5 and -1,10-diaza-18-crown-6 were synthesized with a variety of synthetic methods and fully characterized. Hydrolytic properties of the pendant arms were studied under different pH conditions as well as in the presence and absence of porcine liver esterase enzyme and approximate hydrolysis half lives were determined by 1H NMR technique. In vitro studies on pig liver cell homogenates and living thin chicken liver slices proved that the selected double ester 4b can penetrate liver tissues spontaneously, liberate the free complexing agent N,N′-bis(carboxymethyl)-18-ane-N2O4 (ODDA) inside the cells and are potentially capable of removing lead and other toxic metal ions from the liver. Georg Thieme Verlag Stuttgart.
- Ivanyi, Timea,Lazar, Istvan
-
p. 3555 - 3564
(2007/10/03)
-
- Matrix metalloprotease inhibitors
-
Compounds of formula (I): STR1 as single stereoisomers or mixtures thereof and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as interstitial collagenases, and are useful in the treatment of mammals having disease states alleviated by the inhibition of such matrix metalloproteases, for example arthritic diseases or bone resorption disease, such as osteoporosis.
- -
-
-
- Biosynthesis of porphyrins and related macrocycles. Part 53.1'2 Stereochemical studies on the enzymic formation of hydroxymethylbilane, the precursor of uroporphyrinogen III
-
A new synthesis of porphobilinogen 1 (PBG) is described that allows the preparation of (11R)-[1l-3H1]PBG la and its (1 lS)Tenantiomer Ib. Their enantiomeric purities are determined by degradation of their immediate synthetic precursors by way of 3H-labelled glycines to yield two samples of 3H-labelled glycolic acid 16. The enzyme glycolate oxidase, known to remove HK stereospecifically from the methylene group of glycolic acid in forming glyoxylic acid 17, is then used to assay the configurations of these two samples. Each 3H-labelled PBG la and Ib is converted by hydroxymethylbilane synthase into hydroxymethylbilane 5a and 5b. Methods are devised for the isolation of this labile product from water and for its subsequent degradation to two further samples of glycolic acid. These are assayed enzymically to prove that there is overall retention of configuration as the aminomethyl carbon of PBG 1 enzymically affords the hydroxymethyl centre of the bilane 5. Thus, the two covalent bonds that are formed in this whole process must both involve reactions with retention of configuration or both with inversion. The significance of these results is discussed. The Royal Society of Chemistry 1999.
- Schauder, Jean-Roch,Jendrezejewski, Stefan,Neidhart, Werner L.,Hart, Graham J.,Battersby, Alan R.
-
p. 2691 - 2698
(2007/10/03)
-
- MATRIX METALLOPROTEASE INHIBITORS
-
Compounds of formula (I): STR1 as single stereoisomers or mixtures thereof and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as interstitial collagenases, and are useful in the treatment of mammals having disease states alleviated by the inhibition of such matrix metalloproteases, for example arthritic diseases or bone resorption diseases, such as osteoporosis.
- -
-
-
- Polyglycolate peracid precursors
-
Polyglycolate compounds are provided having the general structure: STR1 wherein n is an integer from 2 to about 10; R is C1-20 linear or branched alkyl, alkoxylated alkyl, cycloalkyl, aryl, alkylaryl, substituted aryl; R' and R" are independently H, C1-20 alkyl, aryl, C1-20 alkylaryl, substituted aryl, and NR3α+, wherein Rα is C1-30 alkyl; and L is a leaving group displaceable in a peroxygen bleaching solution by perhydroxide anion. When this compound is combined with a source of peroxygen in aqueous solution, then a plurality of stain removing peracids are formed. Such peracids are formed substantially sequentially beginning with the carbonyl adjacent to the leaving group L. Thus, a first stain removing peracid having the structure STR2 will be formed in amounts approaching quantitative yield.
- -
-
-
- Substituted azetidinones as anti-inflammatory and antidegenerative agents
-
New substituted azetidinones of the general formula (I) which have been found to be potent elastase inhibitors and thereby useful anti-inflammatory and antidegenerative agents are described. STR1
- -
-
-
- Hydrogen-bond-mediated folding in depsipeptide models of β-turns and α-helical turns
-
The folding of several depsipeptides constructed from α-amino acids [L-proline (P) and L-alanine (A)] and α-hydroxy acids [L-lactic acid (L) and glycolic acid (G)] has been examined in methylene chloride solution by variable- temperature IR spectroscopy. Additional studies have been conducted in some cases, involving variable-temperature 1H NMR spectroscopy and molecular mechanics calculations. The depsipeptides include three-residue molecules (PLL, ALL, and PLG) that can form a 13-membered-ring amide-to-amide hydrogen bond, which, for a peptide backbone, would correspond to a single turn of an α-helix. These depsipeptides can also form 10-membered-ring amide-to-ester hydrogen bonds, which would correspond to β-trun formation for a peptide backbone. For PLL and PLG, distinct N-H stretch bands can be identified for three folding patterns: non-hydrogen-bonded, β-turn, and α-helical turn. IR-based van't Hoff analyses for PLL indicate that the α-helical turn and the β-turn are both modestly enthalpically favored relative to the non-hydrogen-bonded state, but neither turn is enthalpically preferred over the other. For PLG, in contrast, the α-helical turn appears to be enthalpically preferred over both of the alternative folding patterns. Comparison between PLL and ALL indicates that the N-terminal proline residue favors α-helical turn formation. The strengths of amide-to-amide and amide-to-ester hydrogen bonds have been compared in the context of a β-turn geometry by analyzing LG and AG in CH2Cl2. The amide-to-amide hydrogen bond is enthalpically favored by ca. 1.6 kcal/mol, but formation of this enthalpically stronger intramolecular hydrogen bond is more costly entropically. Extrapolation from the behavior of these depsipeptides leads us to predict that for tripeptides in a nonpolar environment, a β-turn will generally be enthalpically preferred over an isolated α-helical turn. β-Turn folding has previously been widely studied in model peptides and depsipeptides; however, the present report appears to represent the first experimental effort to model formation of a single α-helical turn.
- Gallo, Elizabeth A.,Gellman, Samuel H.
-
p. 9774 - 9788
(2007/10/02)
-
- Synthesis of multivalent β-lactosyl clusters as potential tumor metastasis inhibitors
-
A β-lactosyl residue was linked to the amino groups of L-lysyl-L-lysine through spacer arms of three different lengths (C2, C4, and C9) to give trivalent β-lactosyl clusters in order to increase the inhibitory activity of the β-lactosyl group against tumo
- Dean, Barbara,Oguchi, Hisao,Cai, Shaopei,Otsuji, Eigo,Tashiro, Kazuhiro,et al.
-
p. 175 - 192
(2007/10/02)
-
- Dual-Action Penems and Carbapenems
-
Two series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety.Potent, broad-spectrum antibacterial activity was observed for both
- Corraz, Alfred J.,Dax, Scott L.,Dunlap, Norma K.,Georgopapadakou, Nafsika H.,Keith, Dennis D.,et al.
-
p. 1828 - 1839
(2007/10/02)
-
- Synthesis of New Phospholipids Linked to Steroid-Hormone Derivatives Designed for Two-Dimensional Crystallization of Proteins
-
The synthesis of phospholipids 1n-3n, rationally designed for two-dimensional crystallization of progesterone and estradiol receptors, is reported.The structure of theses lipids provides them with essential properties such as fluidity and stability when spread into monolayers at the air/H2O interface, affinity for the protein to be crystallized, and accessibility of the ligand under the lipid monolayer.
- Lebeau, Luc,Oudet, Pierre,Mioskowski, Charles
-
p. 1697 - 1706
(2007/10/02)
-
- Reductive Cross Coupling Reaction of a Glyoxylate with Carbonyl Compounds. A Facile Synthesis of α,β-Dihydroxycarboxylate Based on a Low Valent Titanium Compound
-
On treatment with a low valent titanium compound, a glyoxylate is reductively converted to the titanium enediolate, which reacts with carbonyl compounds to give the corresponding adducts, α,β-dihydroxycarboxylates, in good yields.
- Mukaiyama, Teruaki,Sugimura, Hideo,Ohno, Takashi,Kobayashi, Shu
-
p. 1401 - 1404
(2007/10/02)
-
- Total Synthesis of Pseudomonic Acid C
-
Two approaches to the synthesis of aldehyde 28, a key intermediate in the total synthesis of pseudomonic acid C, were developed.One asymmetric route from the chiral hydroxy ester 11 proceeded in 13 steps via the hydroxy lactone 17.A shorter approach involved the Lewis acid catalyzed cycloaddition of formaldehyde to the chiral diene 23a to give 22a, which was separated from its diastereomer and then converted into 28 in seven steps.The introduction of the C-8 side chain was initially accomplished by Julia coupling of 28 with the sulfone anion derived from 40 to give the olefin 34.The stereoselective preparation of 34 was also carried out, via the ester 46a, by a novel ester enolate Claisen rearrangement of the silyl-protected glycolate ester 44.A third approach directed toward the synthesis of the side chain entailed controlling the C-10 stereochemistry of the benzyl-protected glycolate ester 48 by reduction of a precursor propargyl ketone 27 with Alpine borane.Ester enolate Claisen rearrangement then gave the ester 46b with excellent stereocontrol.
- Barrish, Joel C.,Lee, Hsi Lin,Mitt, Toomas,Pizzolato, Giacomo,Baggiolini, Enrico G,Uskokovic, Milan R
-
p. 4282 - 4295
(2007/10/02)
-
