- Total Synthesis of Plusbacin A3 and Its Dideoxy Derivative Using a Solvent-Dependent Diastereodivergent Joullié-Ugi Three-Component Reaction
-
Full details of our synthetic studies toward plusbacin A3 (1), which is a depsipeptide with antibacterial activity, and its dideoxy derivative are described. To establish an efficient synthetic route of 1, a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) was used to construct trans-Pro(3-OH) in a small number of steps. Two strategies were investigated toward the total synthesis. In the first synthetic strategy, the key steps were the trans-selective JU-3CR and a macrolactonization at the final stage of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3-hexafluoroisopropanol provided the trans products, and the coupling of the fragments to prepare the macrocyclization precursor proceeded smoothly. However, attempts toward the macrolactonization did not provide the desired product. Then, the second strategy that included esterification in an initial stage was investigated. Methods for constructing trans-Pro(3-OH) were examined using a convertible isocyanide, which could be converted to a carboxylic acid required for the following amidation. Ester bond formation was achieved through an intermolecular coupling using a hydroxyl-Asp derivative and the corresponding alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization of the linear peptide gave the cyclic depsipeptide, and then the global deprotection accomplished the total synthesis of 1 and its dideoxy derivative.
- Katsuyama, Akira,Yakushiji, Fumika,Ichikawa, Satoshi
-
p. 7085 - 7101
(2018/07/15)
-
- Synthesis of γ-Lactams by Mild, o-Benzoquinone-Induced Oxidation of Pyrrolidines Containing Oxidation-Sensitive Functional Groups
-
The late-stage oxidation of substituted pyrrolidines offers good flexibility for the construction of γ-lactam libraries, and especially in recent years the methods for functionalization of pyrrolidine have been available. We reported a new strategy for oxidation of pyrrolidines to γ-lactams: reaction of pyrrolidine with an o-benzoquinone gives an N,O-acetal by direct oxidation of the α-C-H bond of the pyrrolidine ring, and then the N,O-acetal is further oxidized by the o-benzoquinone to the γ-lactam. Because the first oxidation occurs selectively at the α-C-H of the pyrrolidine ring, oxidation-sensitive functional groups (allyl-, vinyl-, hydroxyl-, and amino groups) on pyrrolidine ring are unaffected. The synthetic utility of this novel method was demonstrated by the facile syntheses of (S)-vigabatrin and two analogues.
- Rong, Hao-Jie,Cheng, Yong-Feng,Liu, Fan-Fan,Ren, Shu-Jian,Qu, Jin
-
p. 532 - 540
(2017/04/26)
-
- Revisited Mechanistic Implications of the Joullié-Ugi Three-Component Reaction
-
The effect of the solvent on the diastereoselectivity of the Joullié-Ugi three-component reaction (JU-3CR) using an α-substituted five-membered cyclic imine is revisited. The cis and trans isomers were generated in toluene and HFIP, respectively. Hammett
- Katsuyama, Akira,Matsuda, Akira,Ichikawa, Satoshi
-
supporting information
p. 2552 - 2555
(2016/07/06)
-
- STIMULUS-RESPONSIVE POLY(LACTIC-CO-GLYCOLIC)-BASED POLYMERS AND NANOPARTICLES FORMED THEREFROM
-
PLGA-based polymers include pendant nucleophiles protected with photocleavable protecting groups. Upon deprotection, the polymers degrade rapidly via intramolecular cyclization into small molecules. The polymer may be formulated as a nanoparticle, with an encapsulated payload, which may be an imaging agent, a bioactive agent or a pharmaceutical agent.
- -
-
Page/Page column 26
(2016/12/12)
-
- CARBAZOLE-CONTAINING AMIDES, CARBAMATES, AND UREAS AS CRYPTOCHROME MODULATORS
-
The subject matter herein is directed to carbazole-containing amide, carbamate, and urea derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, D, E, G, J, L, M, Q, a, and b are accordingly described. Also provided are pharmaceutical compositions containing the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, complications associated with diabetes, Cushing's syndrome, NASH, NAFLD, asthma, and COPD.
- -
-
Paragraph 0386
(2015/10/28)
-
- INHIBITORS OF HEPATITIS C VIRUS
-
Compounds of Formula I are disclosed, As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.
- -
-
Page/Page column 165
(2014/01/18)
-
- SUBSTITUTED BENZAMIDE DERIVATIVES AS GLUCOKINASE (GK) ACTIVATORS
-
The present invention relates to substituted benzamide derivatives of the general Formula I and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites, and polymorphs and can be use
- -
-
Page/Page column 24
(2012/07/28)
-
- Absorption medium and method for removing sour gases from fluid streams, in particular from flue gases
-
Absorption medium for acid gases comprising an oligoamine (A) of the general formula (I) and a primary or secondary alkanolamine (B) of the general formula (II) in which the weight ratio of oligoamine (A) to the primary or secondary alkanolamine (B) is 0.2 to 4, and also the process for removing acid gases from a gas stream by contacting the gas stream at a pressure of 0.05 to 10 MPa abs with an aqueous solution brought to and maintained at a temperature of 20 to 80° C. of said absorption medium.
- -
-
-
- SUBSTITUTED BENZAMIDE DERIVATIVES AS GLUCOKINASE (GK) ACTIVATORS
-
The present invention relates to substituted benzamide derivatives of the general Formula I and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites, and polymorphs and can be use
- -
-
Page/Page column 50; 51
(2011/02/24)
-
- Design, synthesis, and cyclization of 4-aminobutyric acid derivatives: Potential candidates as self-immolative spacers
-
Self-immolative spacers have gained significant interest in recent years due to their utility in numerous prodrug, sensor and drug delivery systems. However, there are a very limited number of spacers that are capable of undergoing spontaneous and rapid reactions under mild conditions. To address this need, 4-aminobutyric acid derivatives were explored as a potential class of self-immolative spacers. Using a modular approach, eleven N- and α-substituted derivatives of 4-aminobutyric acid were synthesized, and their intramolecular cyclizations to γ-lactams were studied. Kinetics experiments were carried out at physiological pH and temperature, and the observed half-lives for the spacers ranged from 2 to 39 s, depending on the molecular structure. In addition, the pH dependence of the cyclization rate was also explored and it was found that cyclization still occurred rapidly at mildly acidic pH. Therefore, this class of compounds exhibits promise for incorporation into a variety of self-immolative systems where rapid cyclization reactions are desired.
- Dewit, Matthew A.,Gillies, Elizabeth R.
-
experimental part
p. 1846 - 1854
(2011/05/03)
-
- A surprising mechanistic "switch" in Lewis acid activation: A bifunctional, asymmetric approach to α-hydroxy acid derivatives
-
We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, α-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph3P)2PdCl2 was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.
- Abraham, Ciby J.,Paull, Daniel H.,Bekele, Tefsit,Scerba, Michael T.,Dudding, Travis,Lectka, Thomas
-
supporting information; experimental part
p. 17085 - 17094
(2009/04/13)
-
- A concise diastereoselective approach to the left-hand side of batzelladine A
-
A highly diastereoselective three-component coupling reaction has been used in a concise approach to the left-hand side of batzelladine A. The stereoselectivity of this reaction, along with related observations described herein, provides insight into the mechanism of this reaction.
- Davies, Christopher D.,Elliott, Mark C.,Hill-Cousins, Joseph,Khan, Misbah-Ul A.,Maqbool, Tahir,Wood, John L.
-
scheme or table
p. 2028 - 2032
(2009/04/07)
-
- Synthetic Method of Optically Pure (S)-3-Hydroxypyrrolidine
-
A method of preparing optically pure (S)-3-hydroxypyrrolidine is disclosed. The present invention provides a method of economically and industrially preparing optically and chemically pure (S)-3-hydroxypyrrolidine, through a process comprising introducing an amine protecting group by using optically pure 4-amino-(S)-2-hydroxybutylic acid as a starting material, reducing a carboxylic acid group into a primary alcohol, removing the amine protecting group to form an amine salt, halogenating the primary alcohol, and amine cyclization; and through a simple purification process, i.e., distillation under reduced pressure. As another method, the present invention provides a method of preparing optically and chemically pure (S)-3-hydroxypyrrolidine, through a process comprising esterifying optically pure 4-amino-(S)-2-hydroxybutylic acid as a starting material, lactam cyclization, and reduction.
- -
-
Page/Page column 6
(2008/12/08)
-
- SYNTHETIC METHOD OF OPTICALLY PURE (S)-3-HYDROXYPYRROLIDINE
-
A method of preparing optically pure (S)-3-hydroxypyrrolidine is disclosed. The present invention provides a method of economically and industrially preparing optically and chemically pure (S)-3-hydroxypyrrolidine, through a process comprising introducing an amine protecting group by using optically pure 4-amino-(S)-2-hydroxybutylic acid as a starting material, reducing a carboxylic acid group into a primary alcohol, removing the amine protecting group to form an amine salt, halogenating the primary alcohol, and amine cyclization; and through a simple purification process, i.e., distillation under reduced pressure. As another method, the present invention provides a method of preparing optically and chemically pure (S)-3-hydroxypyrrolidine, through a process comprising esterifying optically pure 4-amino-(S)-2-hydroxybutylic acid as a starting material, lactam cyclization, and reduction.
- -
-
Page/Page column 9; 13
(2008/06/13)
-
- Chemoenzymatic enantioselective synthesis of 3-hydroxy-2-pyrrolidinones and 3-hydroxy-2-piperidinones
-
The enantioselective synthesis of 3-hydroxypyrrolidin-2-ones and 3-hydroxy piperidin-2-ones has been carried out in high enantiomeric excess employing immobilized lipase from Pseudomonas cepacia.
- Kamal, Ahmed,Ramana, K. Venkata,Ramana, A. Venkata,Babu, A. Hari
-
p. 2587 - 2594
(2007/10/03)
-
- Synthesis of (S)-vasicol and (S)-3-hydroxy-2-pyrrolidinone
-
Starting from (S)-malic acid, a flexible approach to (S)-3-hydroxy-2-pyrrolidinone and (S)-1-alkyl-3-hydroxy-2-pyrrolidinones was reported. Using this method, the first total syntheses of (-)-vasicol as well as deaminovasicol were accomplished, which allowed the revision and clarification the confusion about the structure of naturally occurring (-)-vasicol.
- Huang, Pei-Qiang,Zheng, Xiao,Wei, Hua
-
p. 1833 - 1841
(2007/10/03)
-
- Suntheses of (3S)-3-hydroxy-2-pyrrolidinone from (S)-malic acid
-
(S)-Malic acid 2 is transformed into (3S)-3-hydroxy-2-pyrrolidinone (8) using hexafluoroacotone os protecting and activating agent. Two alternative routes were developed; key step of both routes is the intramolecular aminolytic cleavage of the lactone rin
- Pires, Raul,Burger, Klaus
-
p. 9213 - 9218
(2007/10/03)
-
- Enantioselective Syntheses of (S)- and (R)-3-Hydroxypyrrolidin-2-ones via Lactate Dehydrogenase Catalysed Reductions of 4-Benzyloxycarbonylamino-2-oxobutanoic Acid
-
The first examples of the BS- and SE-lactate dehydrogenase catalysed reductions of an α-keto acid incorporating a nitrogen containing function in the side chain are described: (S)- and (R)-benzyloxycarbonylamino-2-hydroxybutanoic acids were prepared in good yield and excellent enantioselectivities and were converted to the (S)- and (R)-3-hydroxypyrrolidin-2-ones respectively.
- Bentley, Jonathan M.,Wadsworth, Harry J.,Willis, Christine L.
-
p. 231 - 232
(2007/10/02)
-
- (5R,6S,8R)-6-(1-hydroxyethyl)-2-(3R-pyrrolidin-2-one-3-yl)thiopenem-3-carboxylic acid
-
There is disclosed the compound (5R,6S,8R)-6-(1-hydroxyethyl)-2-(3R-pyrrolidin-2-one-3-yl)thiopenem-3-carboxylic acid, and pharmaceutically acceptable salts and esters as well as compositions containing them and methods for their use.
- -
-
-
- Hydroxylations microbiologiques de pyrrolidinones-2 (note de laboratoire)
-
Microbial hydroxylations of various pyrrolidin-2 ones, especially N-acylated, with Beauveria sulfurescens have been carried out.The regioselectivity depends on the nature of the substituent on the nitrogen atom and the hydroxylation may occur at position 3,4 or 5 of the heterocycle.Hydroxylations at position 3 or 4 occur with low enantioselectivity.
- Srairi, Driss,Maurey, Georges
-
p. 297 - 301
(2007/10/02)
-