- Preparation method of alpha-hydroxyl-gamma-butyrolactone
-
The invention belongs to the field of preparation of organic compounds, and provides a preparation method of alpha-hydroxyl-gamma-butyrolactone. The method is characterized in that malic acid is used as a raw material, and alpha-hydroxyl-gamma-butyrolactone is synthesized with high yield through four steps of reactions, namely, carboxyl and alpha-hydroxyl protection, beta-carboxyl reduction, protecting group removal and internal esterification. The method has the advantages of easily available raw materials, mild reaction conditions and low cost, and is suitable for large-scale preparation of alpha-hydroxy-gamma-butyrolactone.
- -
-
Paragraph 0020; 0023
(2021/06/13)
-
- CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Q, V, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Derivative, and methods of using the Cyclic Phosphate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
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Page/Page column 47-48
(2018/04/11)
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- SYNTHETIC PRECURSOR OF EPOTHILONE FOR IMPROVING PRODUCTION OF EPOTHILONE AND METHOD FOR PREPARING EPOTHILONE USING THE SAME
-
The present invention relates to a compound for increasing production of epothilone in actinomyces, and to a method for producing epothilone with increased yield. The method for producing epothilone of the present invention includes a step of culturing actinomyces in which epothilone-biosynthesizing genes in Sorangium cellulosum including epoD, epoE, epoF, orf6, orf3, and orf14 are introduced in a culture medium. According to the present invention, it is possible to increase the production yield of epothilone in actinomyces, even in actinomyces in which epoA, epoP, epoB, and epoC are not introduced therein.COPYRIGHT KIPO 2016
- -
-
Paragraph 0071; 0072; 0075
(2016/10/10)
-
- Silylation-based kinetic resolution of α-hydroxy lactones and lactams
-
A silylation-based kinetic resolution has been developed for α-hydroxy lactones and lactams employing the chiral isothiourea catalyst (-)-benzotetramisole and triphenylsilyl chloride as the silyl source. The system is more selective for lactones than lactams, and selectivity factors up to 100 can be achieved utilizing commercially available reagents.
- Clark, Robert W.,Deaton, T. Maxwell,Zhang, Yan,Moore, Maggie I.,Wiskur, Sheryl L.
-
supporting information
p. 6132 - 6135
(2014/01/17)
-
- Kinetic resolution of racemic 2-hydroxy-γ-butyrolactones by asymmetric esterification using diphenylacetic acid with pivalic anhydride and a chiral acyl-transfer catalyst
-
Various optically active 2-hydroxy-γ-butyrolactone derivatives are produced via the kinetic resolution of racemic 2-hydroxy-γ-butyrolactones with diphenylacetic acid using pivalic anhydride and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst. Importantly, the substrate scope of this novel protocol is fairly broad (12 examples, s-value; up to over 1000). In addition, we succeeded in disclosing the reaction mechanism to afford high enantioselectivity using theoretical calculations and expounded on the substituent effects at the C-3 positions in 2-hydroxylactones.
- Nakata, Kenya,Gotoh, Kouya,Ono, Keisuke,Futami, Kengo,Shiina, Isamu
-
supporting information
p. 1170 - 1173
(2013/05/21)
-
- Modular and stereoselective synthesis of tetrasubstituted helical alkenes via a palladium-catalyzed domino reaction
-
A highly modular and stereoselective synthesis of tetrasubstituted helical alkenes is accomplished by a Pd-catalyzed norbornene-mediated domino reaction. This protocol features the rapid assembly of four C-C bonds via sequential C-H activations and carbopalladations along with efficient access to enantiopure bromoalkyl aryl alkyne precursors using homologative alkynylation as the key transformation. Three distinct elements of stereoselectivity were observed in the preparation of the chiral helical alkenes: retention of stereochemistry of the substrates, induced helical diastereoselectivity in the alkene formation, and the exclusive exo-facial selectivity of the norbornene incorporation.
- Liu, Hongqiang,El-Salfiti, Mohamed,Chai, David I.,Auffret, Jeremy,Lautens, Mark
-
supporting information; scheme or table
p. 3648 - 3651
(2012/09/08)
-
- HETEROCYCLIC DERIVATIVES AS MODULATORS OF ION CHANNELS
-
The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
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Page/Page column 16
(2009/05/28)
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- HETEROCYCLIC DERIVATIVES AS MODULATORS OF ION CHANNELS
-
The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
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Page/Page column 20
(2009/05/28)
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- Studies towards the total synthesis of (-)-caulerpenynol, a toxic sesquiterpenoid of the green seaweed caulerpa taxifolia
-
The first diastereoselective synthesis of the antimicrobial and cytotoxic agent (-)-caulerpenynol (2) was achieved in relatively few steps from, commercially available (S)-malic acid, Highlights of this synthesis include the nonracemization. of the sensitive a-hydroxy ketone moiety and the proper choice of the protecting groups for critical last deprotection step. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009.
- Commeiras, Laurent,Thibonnet, Jerome,Parrain, Jean-Luc
-
body text
p. 2987 - 2997
(2009/11/30)
-
- Enantioselective synthesis of the PPARα agonist (R)-K-13675 via (S)-2-hydroxybutyrolactone
-
Enantioselective synthesis of enantiomerically pure PPARα agonist (R)-K-13675 can be achieved starting from (S)-2-hydroxybutyrolactone. An important intermediate, 2-(aryloxy)butyrolactone, was prepared by reaction of the phenol with (S)-2-hydroxybutyrolactone in excellent yield without loss of enantiomeric purity using the Mitsunobu reaction, followed by conversion into the 2-(aryloxy)butanoic acid via the 2-(aryloxy)-4-iodobutanoate by cleavage of the lactone on exposure to iodotrimethylsilane, followed by hydrogenolysis and hydrolysis. Georg Thieme Verlag Stuttgart.
- Yamazaki, Yukiyoshi,Araki, Takaaki,Koura, Minoru,Shibuya, Kimiyuki
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p. 1017 - 1022
(2008/12/22)
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- 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
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supporting information; experimental part
p. 17085 - 17094
(2009/04/13)
-
- Epothilon derivatives, method for the production and the use thereof as pharmaceuticals
-
Disclosed are epothilone compounds of formula I, which are useful as pharmaceutical compounds for treating, for example, malignant tumors and chronic inflammatory diseases and are useful in anti-angiogenesis therapy.
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Page/Page column 72
(2010/10/19)
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- First asymmetric total syntheses of (-)-subincanadines A and B, skeletally rearranged pentacyclic monoterpenoid indole alkaloids in Aspidosperma subincanum
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We achieved the first asymmetric total syntheses of novel Aspidosperma indole alkaloids, (-)-subincanadines A and B, which involve an intramolecular diastereoselective Pictet-Spengler cyclization and an intramolecular Nozaki-Hiyama-Kishi reaction as key steps in the total syntheses.
- Suzuki, Kenta,Takayama, Hiromitsu
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p. 4605 - 4608
(2007/10/03)
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- PROCESS FOR THE HYDROGENATION OF ESTERS OF ALPHA-SUBSTITUTED CARBOXYLIC ACIDS
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There is provided a process for the hydrogenation of esters of alpha-substituted carboxylic acids which comprises reacting an ester of an alpha-substituted carboxylic acid with hydrogen in the presence of a catalyst under substantially homogeneous supercritical conditions. Preferably, the ester of an alpha-substituted carboxylic acids is an ester of formula (1): wherein: R1 and R2are each independently an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; and Y is a heteroatom or an optionally substituted heteroatom group. More preferably, the ester of an alpha-substituted is carboxylic acids is an ester of formula (2): wherein: R3 is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; R4and R5 are each independently hydrogen, an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; Y is a heteroatom or an optionally substituted heteroatom group; Q is a functional group; and n 1. Most preferably, the ester of an alpha-substituted carboxylic acids is an ester of formula (3): wherein: R3 and R6 are each independently an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; R4 and R5 are each independently hydrogen, an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; Y is a heteroatom or an optionally substituted heteroatom group; and n 1.
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Page/Page column 10-12
(2008/06/13)
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- Asymmetric reduction of 2-substituted 2-butenolides with reductase from Marchantia polymorpha
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A p68 reductase participating in the asymmetric reduction of the C-C double bond of 2-substituted 2-butenolides was isolated from Marchantia polymorpha. The enzyme reduced 2-substituted 2-butenolides to give (R)-butanolides, and the reduction of citraconic anhydride afforded (R)-methylsuccinic anhydride.
- Shimoda, Kei,Kubota, Naoji
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p. 3827 - 3829
(2007/10/03)
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- Total synthesis of (+)-brasilenyne. Application of an intramolecular silicon-assisted cross-coupling reaction
-
The first enantioselective total synthesis of (+)-brasilenyne (1) has been achieved in 19 linear steps, with 5.1% overall yield from L-(S)-malic acid. The construction of the oxonin core containing a 1,3-cis, cis diene unit was accomplished with a tandem ring-closing metathesis/silicon-assisted intramolecular cross-coupling reaction. In addition, a key propargylic stereogenic center was created through a novel, highly diastereoselective ring opening of a 1,3-dioxolanone promoted by TiCl4. This reaction proceeded through an oxocarbenium ion intermediate and the asymmetric induction was fully controlled by L-malic acid residue. The C(8) stereogenic center was set by a reagent-controlled asymmetric allylboration.
- Denmark, Scott E.,Yang, Shyh-Ming
-
p. 12432 - 12440
(2007/10/03)
-
- Novel epothilone derivatives, method for the preparation thereof and their pharmaceutical use
-
The invention relates to novel epothilone derivatives of general formula (1), wherein R5 represents a halogen atom or a cyano group and the other substituents have the meanings as cited in the description. The novel compounds interact with tubulin by stabilizing formed microtubules. They are capable of influencing the cell division in a phase-specific manner and are well-suited for the treatment of malignant tumors, for example, ovarian, stomach, colon, adeno, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are well-suited for anti-angiogenesis therapy and for the treatment of chronic inflammable medical disorders (psoriasis, arthritis). In order to prevent uncontrolled cell growths as well as to improve the compatibility of medical implants, the inventive epothilone derivatives can be applied to or introduced into polymeric materials. The inventive compounds can be used alone or in order to obtain additive or synergistic effects, in conjunction with additional principles and substance classes that can be used in tumor therapy. 1
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- A METHOD OF PREPARING ENANTIOMERS OF INDOLE-2,3-DIONE-3-OXIME DERIVATIVES
-
The present invention is directed to a method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives.
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-
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- EPOTHILONE DERIVATIVES, METHOD FOR PRODUCING SAME AND THEIR PHARMACEUTICAL USE
-
This invention relates to the new epothilone derivatives of general formula I, 1in which substituents Y, Z R2a, R2b, R3, R4a, R4b, D—E, R5, R6, R7, R8 and X have the meanings that are indicated in more detail in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanomas, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (psoriasis, arthritis). To avoid uncontrolled proliferation of cells and for better compatibility of medical implants, they can be applied or introduced into polymer materials. The compounds according to the invention can be used alone or to achieve additive or synergistic actions in combination with other principles and classes of substances that can be used in tumor therapy.
- -
-
-
- Method for producing optically active alcohols
-
The invention relates to a process for the preparation of optically active alcohols from optically active carboxylic acids by reducing an optically active carboxylic acid with hydrogen in the presence of a catalyst comprising ruthenium and at least one further metal or transition metal having an atomic number in the range of from 23 to 82.
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-
-
- Enantioselective synthesis of α-hydroxy γ-butyrolactones from an ephedrine-derived morpholine-dione
-
An ephedrine-derived morpholine dione is employed in the enantioselective synthesis of (S)-α-hydroxy γ,γ-dimethyl-γ-butyrolactone and (S)-α-hydroxy γ-butyrolactone. A one-pot alkylation/allylation protocol for the stereoselective conversion of the dione to 2-alkyl-2-allyl morpholinones, key intermediates for α-alkyl-α-hydroxy-γ-butyrolactones, is described.
- Pansare, Sunil V,Shinkre, Bidhan A,Bhattacharyya, Annyt
-
p. 8985 - 8991
(2007/10/03)
-
- Intermediates for the synthesis of epothilones and methods for their preparation
-
The invention relates to a method of synthesis for a compound of formula (I), wherein R is a heterocyclyl moiety and X1, X2, X3and X4are, independently of each other, protecting groups, which is appropriate for the synthesis of epothilone B and desoxyepothione B.
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Page column 20
(2010/01/30)
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- Total Syntheses of Epothilones B and D
-
Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.
- Mulzer, Johann,Mantoulidis, Andreas,Oehler, Elisabeth
-
p. 7456 - 7467
(2007/10/03)
-
- Synthesis of polyhydroxylated pyrrolizidine alkaloids of the alexine family by tandem ring-closing metathesis-transannular cyclization. (+)-Australine
-
Dienes 23 and 54, prepared from epoxy alcohol 9 via oxazolidinones 15 and 51, respectively, underwent ring-closing metathesis with Grubbs's catalyst to give azacyclooctenes 26 and 55. Treatment of each azacyclooctene with m-chloroperoxybenzoic acid afforded β-epoxide 28 from 26 and α-epoxide 61 from 60. Basic hydrolysis of each of these oxazolidinones was accompanied by transannular attack at the epoxide by nitrogen, resulting in 2-(O-benzyl)-7-deoxyalexine (29) and 1,2-di-(O-benzyl)australine (62). The latter was converted to the alkaloid australine (3) upon hydrogenolysis. Attempts to effect ring-closing metathesis of dienes 37, 38, and 46 were unsuccessful, suggesting that, while one allylic oxygen substituent can be tolerated by Grubbs's catalyst, two cannot.
- White,Hrnciar
-
p. 9129 - 9142
(2007/10/03)
-
- Syntheses of fluorinated ligands to probe binding of antigenic determinants of Vibrio cholerae O:1, serotypes Inaba and Ogawa, to antibodies
-
Derivatives of methyl α-glycosides of antigenic determinants of Vibrio cholerae O:1, serotypes Inaba and Ogawa, specifically fluorinated at position 2' or 4' have been synthesized by coupling the appropriately fluorinated derivatives of 3-deoxy-L-glycero-tetronic acid with the methyl α-glycosides of perosamine. The compound having the fluorine atom at position 2 was obtained by electrophilic addition of fluorine to the glycal derived from the parent antigenic determinant, serotypes Inaba, using Selectfluor((TM)) as a fluorination reagent. Copyright (C) 2000 Elsevier Science Ltd.
- Chang, Alex H.C.,Horton, Derek,Kovac, Pavol
-
p. 595 - 606
(2007/10/03)
-
- Syntheses of (-)-epothilone B
-
Two efficient routes for the total synthesis of (-)-epothilone B are reported. One strategy is based on ring-closing metathesis, and a second synthesis on a macrolactonization. The key fragments are available on large scale to provide sufficient material for biological tests. Thiazole fragment 4 was obtained by an improved route starting from (S)-malic acid. The first synthesis is based on our preceding paper. The critical trisubstituted double bond C12-13 in our second approach was constructed by a highly efficient Pd- mediated coupling reaction. Ring closure was achieved by macrolactonization.
- Schinzer, Dieter,Bauer, Armin,Schieber, Jennifer
-
p. 2492 - 2500
(2007/10/03)
-
- Synthesis of epothilones: Stereoselective routes to epothilone B
-
In connection with our studies of the total syntheses of epothilones we report our efforts on the syntheses of epothilone B using a macro-lactonization and a metathesis approach. Key reaction for the solution of the acyclic stereoselection is a stereoselective aldol reaction.
- Schinzer, Dieter,Bauer, Armin,Schieber, Jennifer
-
p. 861 - 864
(2007/10/03)
-
- Preparation of chiral pyrrolidinone derivatives
-
A process for preparing a compound of formula IIa or IIb: STR1 wherein R2, R3, R4 and R5 independently represent hydrogen or C1 -C4 alkyl; and A is an optionally substituted aromatic or heteroaromatic ring system; the process comprising the steps of: (a) reacting a racemic mixture of a compound of formula II: STR2 wherein R2, R3, R4, R5 and A are as defined for formulae IIa and IIb; with a sterically hindered chiral esterifying agent to form enantiomers of formulae IIIa and IIIb: STR3 wherein R2, R3, R4, R5 and A are as defined for formulae IIa and IIb and R15 is a chiral sterically hindered residue; b) separating the diastereoisomers of formulae IIIa and IIIb; and (c) converting the diastereoisomers of formulae IIIa and IIIb separately to compounds of formulae IIa and IIb respectively by acid or base hydrolysis. If required, the unwanted enantiomer of formula IIa or IIb may be inverted to give the preferred isomer.
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- A new efficient synthesis of nicotianamine and 2′-deoxymugineic acid
-
Nicotianamine and 2′-deoxymugineic acid, phytosiderophores, have been efficiently synthesized, which will be suitable for large scale production of these plant physiologically important compounds. The synthetic method for 2′,3″-dideoxy-3″-oxomugineic acid was also investigated.
- Shioiri, Takayuki,Irako, Naoko,Sakakibara, Sachiko,Matsuura, Fumiyoshi,Hamada, Yasumasa
-
p. 519 - 530
(2007/10/03)
-
- Stereocontrolled synthesis of the C(1)-C(11) subunit of the Iejimalides
-
An enantioselective synthesis of the C(1)-C(11) subunit of the iejimalides has been accompished through a combination of an asymmetric Horner-Wadsworth-Emmons condensation and a chiral pool approach.
- Mendlik, Matthew T.,Cottard, Muriel,Rein, Tobias,Helquist, Paul
-
p. 6375 - 6378
(2007/10/03)
-
- New N-acylating reagents derived from 3-deoxy-L-glycero-tetronic acid
-
Commercially available N-Boc-4-O-benzyl-L-homoserine was treated with trifluoroacetic acid and the corresponding, N-deprotected derivative was submitted to deamination to give 4-O-benzyl-3-deoxy-L-glycero-tetronic acid (5). In another approach to 3-deoxy-L-glycero-tetronic acid protected at position 4, the carboxylic groups in L-malic acid were reduced, and the resulting triol was benzylidenated. Oxidation of the 2,4-O-benzylidene derivative formed with CrO3-pyridine complex in the presence of t-butyl alcohol gave t-butyl 2,4-O-benzylidene-3-deoxy-L-glycero-tetronate (13). The latter was saponified with aqueous sodium hydroxide to give, after Na+ exchange for H+, 2,4-O-benzylidene-3-deoxy-L-glycero-tetronic acid (15). Opening of the acetal ring in 13, followed by hydrolytic cleavage of the t-butyl ester function gave material indistinguishable from 5 obtained in the original way. When tested for their efficiency of N-acylation of derivatives of D-perosamine, both acids 5 and 15 gave the corresponding tetronamido derivatives in high yields.
- Lei, Ping-Sheng,Ogawa, Yuji,Kovac, Pavol
-
p. 485 - 500
(2007/10/03)
-
- Saponaceolides: Differential cytotoxicity and enantioselective synthesis of the right-hand lactone moiety
-
The enantioselective synthesis of the right-hand lactone moiety 5 of saponaceolide B, 2, is described. The mean graph profiles of 5 do not match the characteristic patterns of differential cytotoxicity of saponaceolides A, 1, and B, 2, in the NC1 human disease-oriented tumor screening panel, pointing out the need of the entire saponaceolide structure for maintaining the specificity and potency of the antitumor activity. En route to 5 several useful chiral building blocks, such as compounds 6, 10, 19, 27, and 28 were prepared.
- Vidari,Lanfranchi,Sartori,Serra
-
p. 2977 - 2990
(2007/10/03)
-
- Stereochemistry of remote dianion addition to imines. Application to the synthesis of (1S, 8aS)-1-hydroxyindolizidine
-
A stereoselective route to (1S, 8aS)-1-hydroxyindolizidine is reported herein that incorporates as a pivotal step the diastereoselective addition of the dianion of 4-(phenylsulfonyl)butanoic acid (4-PSBA) to a chiral α-benzyloxymethyl imine.
- Green, Diana L. C.,Kiddle, James J.,Thompson, Charles M.
-
p. 2865 - 2874
(2007/10/02)
-
- Total syntheses of (2S)-antafumicins A and B.
-
To clarify the absolute configurations of antafumicins A and B, which are antifungal substances from Aspergillus niger NH-401, the total synthesis of (2S)-antafumicins was accomplished by starting from (S)-malic acid in 12 steps. Based upon the physicochemical data of the synthetic samples, the absolute configurations of naturally occurring antafumicins A and B were determined as (2R,4S)- and (2R,4R)-4-(3-acetyl-2,6-dihydroxyphenyl)-2-methoxy-4-butanolide, respectively.
- Fujimoto,Ukita,Miyagawa,Tsurushima,Irie,Nishimura,Ueno
-
p. 1627 - 1631
(2007/10/02)
-
- SYNTHESIS OF THE METHYL α-GLYCOSIDE OF THE INTRACATENARY DISACCHARIDE REPEATING UNIT OF THE O-POLYSACCHARIDE OF VIBRIO CHOLERAE O:1. A COMPARISON OF TWO ASSEMBLY STRATEGIES
-
The two strategies engaged in the construction of the title disaccharide 17 comprise: 1. assembly of a diamino disaccharide and its N-acylation using chiral reagents to introduce the 4-(3-deoxy-L-glycero-tetronyl) group, followed by deprotection, and 2. preparation of a glycosyl acceptor and a glycosyl donor both having the chiral 3-deoxy-L-glycero-tetronamido group already in place, their condensation to give a fully substituted disaccharide, and deprotection.Accordingly, the crystalline diamino disaccharide methyl 2-O-(4-amino-3-O-benzyl-4,6-dideoxy-α-D-mannopyranosyl)-4-amino-3-O-benzyl-4,6-dideoxy-α-D-mannopyranoside, (14), was prepared from the known diazido disaccharide 12, and treated with the lactone 30, or its acetylated or benzylated analogs 31 and 32, respectively, as the N-acylating reagents.Subsequent deprotection of the respective products applying standard chemistry gave 17.Alternatively, the methyl α-glycoside of the monomeric intracatenary repeating unit of Vibrio cholerae O:1 (2) was converted to the fully benzoylated glycosyl chloride 26, and the latter glycosyl donor was condensed with methyl 3-O-benzyl-4,6-dideoxy-4-(2,4-di-O-benzoyl-3-deoxy-L-glycero-tetronamido)-α-D-mannopyranoside (24), to give the corresponding, fully protected derivative 27.Deprotection then readily gave 17.It appears that the title disaccharide can be most efficiently synthesized using synthons 24 and 26.The lactones 30 and 32 appear to be promising acylating reagents for the introduction of the 3-deoxy-L-glycero-tetronamido group when higher oligosaccharides in this series will be synthesized via their (poly)amino precursors.
- Gotoh, Makoto,Kovac, Pavol
-
p. 1193 - 1214
(2007/10/02)
-
- Homochiral 2,4-Disubstituted 1,3-Dioxanes from (S)-(-)-Malic Acid: Stereoselective Synthesis and Investigation of the NMDA Receptor Affinity of All Four Stereoisomers
-
Starting from a single enantiomerically pure compound, (S)-(-)-malic acid, all four stereoisomeric 4-dimethylaminomethyl-2-phenyl-1,3-dioxanes (S,S)-15, (R,R)-15 (S,R)-16, and (R,S)-16 are prepared: Transacetalisation of benzaldehyde dimethyl acetal (6b) with (S)-(-)-methyl 2,4-dihydroxybutyrate (7a), which is obtained by chemoselective BH3 reduction of (S)-(-)-malic acid monoester 8b, yields the diastereomeric 1,3-dioxane derivatives (S,S)-10 and (R,S)-11 in a 85:15 ratio.LDA deprotonation of (S,S)-10 followed by protonation leads to C-4 epimerisation .The thermodynamically controlled 88:12 equilibrium of (R,R)-10 and (S,R)-11 is reached by treatment of (S,R)-11 with acid.Aminolysis with dimethylamine and subsequent LiAlH4 reduction transform the four stereoisomeric esters (S,S)-10, (R,R)-10, (S,R)-11 and (R,S)-11 to give the amines (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16, respectively.In the 3H-(+)-MK 801 displacement experiment (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16 show a very little affinity to the phencyclidine binding site in the cation channel associated with the NMDA receptor. - Key Words: Butyric acid derivatives, (S)-(-)-24-dihydroxy-/ 1,3-Dioxanes/ NMDA antagonists, noncompetitive
- Wuensch, Bernhard,Diekmann, Heike,Hoefner, Georg
-
p. 1273 - 1278
(2007/10/02)
-
- Two enantioselective syntheses of a precursor of the biologically most active isomer of CGA 80000 (clozylacon)
-
The unchlorinated precursor 4 of CGA 80000 (1) was synthesized enantioselectively by two conceptionally different routes: a) by a 'chiral pool' approach starting from L-malic acid and b) by enantioselective hydrogenation of an enamide intermediate, catalyzed by chiral Rh- or Ru-phosphine-complexes.
- Buser,Pugin,Spindler,Sutter
-
p. 5709 - 5716
(2007/10/02)
-
- 3- or 4-substituted oxotremorine derivatives
-
This disclosure describes novel 3 or 4 substituted oxotremorine derivatives having polar substituted oxygen or sulfur groups. The compounds have cholinergic activity. Also disclosed are methods for treating diseases of the central nervous system in mammals employing the compounds, pharmaceutical preparations containing the compounds and processes for the production of the compounds.
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-
-
- Synthesis and Nuclear Magnetic Resonance Studies of Some N-Acylated Methyl 4-Amino-4,6-dideoxy-α-D-mannopyranosides
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The methyl α-glycosides of 4-amino-4,6-dideoxy-D-mannopyranose (perosamine), N-acylated with either formic, acetic, or (S)-2,4-dihydroxybutanoic acid, have been synthesized.The (1)H and (13)C n.m.r. spectra of these substances and the parent, non-N-acylated glycoside, demonstrated how the chemical shifts are influenced by the N-acylation.The N-formyl derivative occured in two conformations, s-cis and s-trans, and the free-energy barrier between these, 86.9 kJ mol-1, was defined by dynamic n.m.r. spectroscopy.
- Kenne, Lennart,Unger, Per,Wehler, Thomas
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p. 1183 - 1186
(2007/10/02)
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- SYNTHESIS OF THE OPTICALLY ACTIVE FORMS OF 4,10-DIHYDROXY-1,7-DIOXASPIROUNDECANE AND THEIR CONVERSION TO THE ENANTIOMERS OF 1,7-DIOXASPIROUNDECANE, THE OLIVE FLY PHEROMONE
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Both the enantiomers of 1,7-dioxaspiroundecane, the major component of the pheromone of the olive fly (Dacus oleae), were synthesized from (S)-malic acid.
- Mori, Kenji,Uematsu, Tamon,Yanagi, Kazunori,Minobe, Masao
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p. 2751 - 2758
(2007/10/02)
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