- A new pre-column derivatization for valienamine and beta-valienamine using o-phthalaldehyde to determine the epimeric purity by HPLC and application of this method to monitor enzymatic catalyzed synthesis of beta-valienamine
-
Valienamine and β-valienamine are representative C7?N aminocyclitols with significant glycosidase inhibition activity that have been developed as important precursors of drugs for diabetes and lysosomal storage diseases, respectively. The quantitative analysis of these chiral compounds is crucial for asymmetric in vitro biosynthetic processes for converting valienone into valienamine epimers using aminotransferase. Here, we developed an efficient and sensitive method for separation and quantitative analysis of chiral valienamine using reversed-phase high-performance liquid chromatography (HPLC) through o-phthalaldehyde (OPA) pre-column derivatization of the analytes. The epimers were derivatized by OPA in borate buffer (pH 9.0) at room temperature for 30 s, separated on an Eclipse XDB-C18 (5?μm, 4.6?×?150?mm) column, eluted with 22% acetonitrile at 30?°C for 18?min, and detected by a fluorescence detector using 445?nm emission and 340?nm excitation wavelengths. The average resolution of the epimers is 3.86, and the concentration linearity is in the range of 0.02–20?μg/ml. The method proved to be effective, sensitive, and reliable with good intra- and inter-day precision and accuracy, and successfully evaluated the enantiopreference and catalytic capability of the potential aminotransferases on an unnatural prochiral substrate, facilitating the design of an asymmetric biosynthetic route for optically pure valienamine and β-valienamine.
- Cui, Li,Guan, Xiao-Qing,Liu, Zhang-Min,Fan, Liu-Yin,Li, Qian,Feng, Yan
-
-
Read Online
- Improved Stereoselective Syntheses of (+)-Valiolamine and (+)-Valienamine Starting from (–)-Shikimic Acid
-
Improved stereoselective syntheses of the target compounds (+)-valiolamine 1 and (+)-valienamine 2 starting from naturally abundant (–)-shikimic acid are described. A common key intermediate compound 7 was first synthesized from (–)-shikimic acid in 9 steps. The compound 7 was then converted to (+)-valiolamine 1 in 3 steps, and was also converted to (+)-valienamine 2 in 4 steps. In summary, (+)-valiolamine 1 and (+)-valienamine 2 were synthesized from (–)-shikimic acid in 12 (or 13) steps in 40% and 39% overall yields, respectively. The present syntheses are more practical and might be important for the potential industrial preparations of pharmaceutically valuable (+)-valiolamine 1 and (+)-valienamine 2.
- Li, Fenglei,Ding, Wei,Quan, Na,Wu, Jiajia,He, Yungang,Zhu, Xingliang,Shi, Xiaoxin,Zhao, Jianhong
-
-
Read Online
- Stereoselective synthesis of (+)-valienamine starting from the naturally abundant (-)-shikimic acid
-
A stereoselective synthesis of the pharmaceutically useful pseudo-aminosugar (+)-valienamine 1 is described. Epoxide 2 was first prepared via four steps in 79.7% overall yield starting from the naturally abundant (-)-shikimic acid. Epoxide 2 was then converted into the vicinal dihydroxyl compound 3 in 96% yield via a highly regio- and stereoselective water-mediated epoxide opening. Compound 3 was transformed into compound 4 in 86% yield over two steps via ester-reduction and benzylation of the three hydroxyl groups. Compound 4 was converted into azido compound 5 in 90% yield via an SN2-type nucleophilic substitution of the OMs leaving group with sodium azide. Ruthenium-catalyzed stereoselective dihydroxylation of compound 5 afforded dihydroxyl compound 6 in 91% yield. Compound 6 was transformed into compound 7 in 92% yield via selective mono-acetylation of the less-hindered hydroxyl group. Dehydration of tertiary alcohol 7 via an acid-mediated elimination furnished olefinic compound 8 in 85% yield. Finally, compound 8 was converted into the title compound 1 in 91% yield over two steps via deprotection and Lindlar-catalyst-promoted highly selective hydrogenation of the azido group (N3) in the presence of a double bond. (+)-Valienamine 1 was thus synthesized starting from the naturally abundant (-)-shikimic acid via 13 steps in 38.3% total yield.
- Ding, Wei,Yu, Jiang-Ping,Shi, Xiao-Xin,Nie, Liang-Deng,Quan, Na,Li, Feng-Lei
-
-
Read Online
- Novel synthesis method of violienamine
-
The invention provides a novel synthesis method of violienamine. Specifically, the invention provides the novel synthesis method comprising the following steps: carrying out double-bond epoxidation reaction on an intermediate I to obtain an intermediate II; then carrying out rearrangement reaction on the intermediate I to obtain an intermediate III, i.e., violienamine with an amino protection group; removing the protection group from the intermediate II to obtain violienamine.
- -
-
-
- Preparation method of high-purity validamine
-
Validamine and valienamine are important chemical raw materials but have high separation cost and complex separation process. The invention discloses a preparation method validamine, which includes the steps of: 1) hydrolyzing validoxylamine A through an NBS chemical method by adding the validoxylamine A and NBS to water as a solvent according to certain molar ratio, and performing a reaction for 4 h at 25 DEG C; 2) carrying out adsorption separation to the reaction product through a weak-acidic cation exchange resin, and concentrating the product to obtain a mixture of the validamine and valienamine; 3) under catalysis by a heavy metal catalyst, performing hydrogenation to the mixture, performing adsorption separation to the reaction product through a weak-acidic cation exchange resin, concentrating the product, and vacuum-drying the concentrate to obtain a high-quality validamine sample.
- -
-
Paragraph 0020; 0021; 0023; 0024; 0052; 0053
(2018/01/12)
-
- Amino sugar intermediate preparation method
-
The present invention discloses a method for preparing a compound amino sugar intermediate represented by a formula I through a one-step method, a composition containing the compound represented by the formula I and a compound represented by a formula A and obtained through the method, and uses of the composition in preparation of type 2 diabetes treating drugs. The formulas I and A are defined in the specification.
- -
-
Paragraph 0075-0076
(2017/02/17)
-
- Total synthesis of (+)-valienamine and (-)-1-epi-valienamine via a highly diastereoselective allylic amination of cyclic polybenzyl ether using chlorosulfonyl isocyanate
-
The total synthesis of (+)-valienamine and (-)-1-epi-valienamine was concisely accomplished from readily available d-glucose via a highly diastereoselective amination of chiral benzylic ether using chlorosulfonyl isocyanate, intramolecular olefin metathesis, and diastereoselective reduction of cyclic enone using l-Selectride as the key steps.
- Li, Qing Ri,Kim, Seung In,Park, Sook Jin,Yang, Hye Ran,Baek, A Reum,Kim, In Su,Jung, Young Hoon
-
p. 10384 - 10390
(2013/11/19)
-
- A C2-symmetric pool based flexible strategy: An enantioconvergent synthesis of (+)-valiolamine and (+)-valienamine
-
A new enantioconvergent strategy directed toward the synthesis of glucosidase inhibitors was developed by using a C2-symmetric element within the chiral pool and by applying an iodine-promoted cyclization of an unsaturated carbonimidothioate for the regio- and diastereocontrolled installation of amino and hydroxy units. Not only does this simple flexible strategy provide a convergent concise approach to (+)-valiolamine (1), but it can also be readily adopted for the synthesis of (+)-valienamine (2). Commercially available and cheap C2-symmetric D-tartaric acid served as the chiral building block. Copyright
- Lo, Hong-Jay,Chen, Cheng-Yih,Zheng, Wei-Lin,Yeh, Shang-Ming,Yan, Tu-Hsin
-
experimental part
p. 2780 - 2785
(2012/07/14)
-
- A concise synthetic approach to (+)-valienamine starting from Garner's aldehyde
-
A synthesis of (+)-valienamine was achieved starting from Garner's aldehyde in ten steps and 23% overall yield. A unique feature of the synthetic route is that an acyclic precursor was constructed, using diastereoselective antireductive coupling reaction of alkyne and Garner's aldehyde as the key step, which was then cyclized in an intramolecular aldol reaction to form the valienamine skeleton. Georg Thieme Verlag Stuttgart · New York.
- Zhou, Bing,Luo, Zhi,Lin, Sui,Li, Yuanchao
-
supporting information; experimental part
p. 913 - 916
(2012/05/20)
-
- Methods of producing validamycin A analogs and uses thereof
-
This disclosure relates to validamycin A biosynthesis and in particular, to methods of producing validamycin A analogs and uses thereof. In a particular example, a method for making a validamycin A analog includes transforming a host cell with one or more recombinant DNA vectors to produce a valN-inactivated mutant; and culturing the valN-inactivated mutant in a culture medium to produce a validamycin A analog, such as 1,1′-bis-valienamine and validienamycin, and their conversion to valienamine. The present disclosure further relates to compositions including such compounds as well as methods of using the compositions, such as for antifungal agents.
- -
-
Page/Page column 28
(2012/02/02)
-
- A flexible strategy based on a C2-symmetric pool of chiral substrates: Concise synthesis of (+)-valienamine, key intermediate of (+)- pancratistatin, and conduramines A-1 and E
-
A new strategy invoking a new application of the [3,3] sigmatropic rearrangement of allylic azides and the presence of a C2 symmetry element within a pool of chiral substrates was evolved. Not only does this simple flexible strategy provide a concise approach to (+)-valienamine, but it also can readily be adopted for the synthesis of conduramines A-1 and E and the enantiopure azido carbonate 4, a key intermediate of (+)-pancratistatin.
- Chang, Yuan-Kang,Lo, Hong-Jay,Yan, Tu-Hsin
-
supporting information; experimental part
p. 4278 - 4281
(2010/01/16)
-
- Stereoselective total synthesis of (+)-valienamine and (+)-4-epi- valienamine via a ring-closing enyne metathesis protocol
-
Stereoselective total synthesis of (+)-valienamine is reported utilizing Sharpless asymmetric dihydroxylation, diastereoselective Carreira alkynylation, and ring-closing enyne metathesis (RCEYM) as key steps from L-serine. A similar strategy is also reported for the first total synthesis of (+)-4-epi- valienamine. Georg Thieme Verlag Stuttgart.
- Radha Krishna, Palakodety,Srinivas Reddy
-
body text
p. 209 - 212
(2009/06/23)
-
- Search for α-glucosidase inhibitors: New N-substituted valienamine and conduramine F-1 derivatives
-
A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (±)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward α-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues.
- Lysek, Robert,Schuetz, Catherine,Favre, Sylvain,O'Sullivan, Anthony C.,Pillonel, Christian,Kruelle, Thomas,Jung, Pierre M.J.,Clotet-Codina, Imma,Este, Jose A.,Vogel, Pierre
-
p. 6255 - 6282
(2007/10/03)
-
- Biosynthesis of the validamycins: Identification of intermediates in the biosynthesis of validamycin A by Streptomyces hygroscopicus var. limoneus
-
To study the biosynthesis of the pseudotrisaccharide antibiotic, validamycin A (1), a number of potential precursors of the antibiotic were synthesized in 2H, 3H-, or 13C-labeled form and fed to cultures of Streptomyces hygroscopicus var. limoneus. The resulting validamycin A from each of these feeding experiments was isolated, purified and analyzed by liquid scintillation counting, 2H- or 13C NMR or selective ion monitoring mass spectrometry (SIM-MS) techniques. The results demonstrate that 2-epi-5-epi-valiolone (9) is specifically incorporated into 1 and labels both cyclitol moieties. This suggests that 9 is the initial cyclization product generated from an open-chain C7 precursor, D-sedoheptulose 7-phosphate (5), by a DHQ synthase-like cyclization mechanism. A more proximate precursor of 1 is valienone (11), which is also incorporated into both cyclitol moieties. The conversion of 9 into 11 involves first epimerization to 5-epi-valiolone (10), which is efficiently incorporated into 1, followed by dehydration, although a low level of incorporation of 2-epi-valienone (15) is also observed. Reduction of 11 affords validone (12), which is also incorporated specifically into 1, but labels only the reduced cyclitol moiety. The mode of introduction of the nitrogen atom linking the two pseudosaccharide moieties is not clear yet. 7-Tritiated valiolamine (8), valienamine (2), and validamine (3) were all not incorporated into 1, although each of these amines has been isolated from the fermentation, with 3 being most prevalent. Demonstration of in vivo formation of [7-3H]validamine ([7-3H]-3) from [7-3H]-12 suggests that 3 may be a pathway intermediate and that the nonincorporation of [7-3H]-3 into 1 is due to a lack of cellular uptake. We thus propose that 3, formed by amination of 12, and 11 condense to form a Schiff base, which is reduced to the pseudodisaccharide unit, validoxylamine A (13). Transfer of a D-glucose unit to the 4′-position of 13 then completes the biosynthesis of 1. Other possibilities for the mechanism of formation of the nitrogen bridge between the two pseudosaccharide units are also discussed.
- Dong,Mahmud,Tornus,Lee,Floss
-
p. 2733 - 2742
(2007/10/03)
-
- Synthesis of [7-3H]valienamine, [7-3H]valienone, [7-3H]valiolamine and [7-3H]valiolone from validamycin A
-
To investigate the biosynthetic pathway to the cyclitol moieties of acarbose and validamycin A, [7-3H]valienamine, [7-3H]valienone, [7-3H]valiolamine and [7-3H]valiolone were synthesized as plausible precursors. Valienamine together with validamine was isolated from the degradation of validamycin A by Flavobacterium saccharophilum and served as starting material for the synthesis. Validamine was removed partially at the stage of tritylation and completely after the oxidation of the primary hydroxy group at C-7 to the aldehyde. The resulting valienamine aldehyde was reduced with tritiated sodium borohydride to produce [7-3H]valienamine. The latter was converted to [7-3H]valiolamine by a synthetic route described in the literature. The 3H-labeled amines were oxidized to [7-3H]valienone and [7-3H]valiolone, respectively, using 3,5-di-tert-butyl-1,2-bezoquinone (DBQ) followed by hydrolysis with oxalic acid.
- Lee, Sungsook,Tornus, Ingo,Dong, Haijun,Groeger, Stefan
-
p. 361 - 372
(2007/10/03)
-
- Enantiospecific syntheses of valienamine and 2-epi-valienamine
-
Cyclic sulfite 10, readily available from (-)-quinic acid (3) in 10 steps, was ring opened regio- and stereospecifically with azide anion to give (1S,2R,3R,4R)-1-azido-3,4-di-O-benzyl-5-(benzyloxymethyl)cyclohex-5-ene- 2,3,4-triol (11). Deprotection of 11 afforded, for the first time, 2- epivalienamine (2), which was isolated as penta-N,O-acetyl-2-epi-valienamine (14). The configuration of the free hydroxy group in 11 was inverted by a two-step sequence to give the blocked valienamine 19 that was deprotected to give valienamine (1), isolated as penta-N,O-acetylvalienamine (21). This approach furnished (+)-valienamine (1) in 16 steps (7% overall yield) and recorded the first synthesis of 2-epi-valienamine (2) in 13 steps (11% overall yield).
- Shing, Tony K. M.,Li, Tin Y.,Kok, Stanton H.-L
-
p. 1941 - 1946
(2007/10/03)
-
- Carbasaccharides via ring-closing alkene metathesis. A synthesis of (+)- valienamine from D-glucose
-
(+)-Valienamine (16) was prepared in seven steps and in an overall yield of 17% from commercially available 2,3,4,6-tetra-O-benzyl-D-glucopyranose. Stereoselective addition of vinylmagnesium bromide to the 1,3,4,5-tetra-O- benzyl-6,7-dideoxy-L-xylo-hept-6-en-2-ulose (2) gave diene 3 (86%). Ring- closing alkene metathesis of 3 in the presence of 0.15 equiv, of Grubb's catalyst 1 gave the cyclohexene 4 (58%), that was converted into (+)- valienamine (16) in three steps and in 47% yield. Similarly, ring-closing alkene metathesis of the D-mannose-derived diene 20 gave the cyclohexene 21 (89%).
- Kapferer, Peter,Sarabia, Francisco,Vasella, Andrea
-
p. 645 - 656
(2007/10/03)
-
- Total synthesis of (±)- and (+)-valienamine via a strategy derived from new palladium-catalyzed reactions
-
A new strategy toward glycosidase inhibitors, represented by valienamine, which is such an inhibitor itself as well as a critical unit of pseudooligosaccharides that function this way, evolved from two newly developed palladium-catalyzed reactions. The applicability of a palladium(0)-catalyzed net regioselective cis-hydroxyamination derives from the reaction of vinyl epoxides with isocyanates. The utilization of a cocatalyst in this reaction is required in this case and may prove generally useful. A bidentate phosphate proved to be the most effective ligand. The requisite substrate was available via a Diels-Alder protocol and allowed the obtention of (±)-valienamine in only seven steps. The inability to perform the Diels-Alder reaction asymmetrically led to a different asymmetric synthesis of the pivotal epoxide intermediate in enantiomerically pure form, which derived from asymmetric palladium-catalyzed reactions. Using the desymmetrization of meso enedicarboxylates, the net equivalence of an asymmetric cis-hydroxycarboxylation led to the enantiomerically pure desired epoxide. (+)-Valienamine was available in 14 steps by this route.
- Trost, Barry M.,Chupak, Louis S.,Luebbers, Thomas
-
p. 1732 - 1740
(2007/10/03)
-
- INTRAMOLECULAR AMINO DELIVERY REACTIONS FOR THE SYNTHESIS OF VALIENAMINE AND ANALOGUES
-
Iodocyclization and sigmatropic rearrangement reactions of N-substituted carbonimidothioates are used to prepare valienamine (1), 7-norvalienamine (8), and the valienamine-based pseudo-disaccharide 12. Key words: carbonimidothioates; iodocyclization; rearrangement; glucosidase inhibitors; pseudo disaccharides
- Knapp, Spencer,Naughton, Andrew B. J.,Dhar, T. G. Murali
-
p. 1025 - 1028
(2007/10/02)
-
- STEREOCONTROLLED SYNTHESIS OF (+)-VALIENAMINE
-
(+)-Valienamine, 1, constituent of antibiotics and α-glucosidase inhibitors, is synthesized through a simple and stereoselective procedure, starting from the easily available enone 3.A stereoselective access to 6-epivalienamine, 2, from the same precursor is also described.
- Nicotra, Francesco,Panza, Luigi,Ronchetti, Fiamma,Russo, Giovanni
-
p. 577 - 580
(2007/10/02)
-
- SYNTHESES OF VALIDAMINE, EPI-VALIDAMINE, AND VALIENAMINE, THREE OPTICALLY ACTIVE PSEUDO-AMINO-SUGARS, FROM D-GLUCOSE
-
Using as a key reaction a Michael-type addition reaction to nitro-olefins or a substitution reaction for an acetoxyl residue at the β-position of the nitro group in pseudo-nitro-sugar, three optically active pseudo-amino-sugars: validamine, epi-validamine, and valienamine, were synthesized from D-glucose.KEYWORDS--pseudo-amino-sugar optically active; validamine; epi-validamine; valienamine; pseudo-amino-sugar synthesis; Michael-type addition, pseudo-nitro-sugar
- Yoshikawa, Masayuki,Cha, Cheon Bae,Okaichi, Yoshihiko,Takinami, Yoshihiko,Yokokawa, Yoshihiro,Kitagawa, Isao
-
p. 4236 - 4239
(2007/10/02)
-
- Cyclitol Reactions, V. - Synthesis of Enantiomerically Pure Valienamine from Quebrachitol
-
An enantioselective synthesis of Valienamine (86) from quebrachitol (L-2O-methyl-chiro-inositol) (1) is described.Valienamine (86) is an unsaturated branched-chain aminocyclitol found in the central structural unit of the antidiabetic drug acarbose.Techniques for the introduction of side chains, azido groups, and double bonds into inositol systems are investigated.The methods developed in this connection are applied in the synthesis of valienamine.
- Paulsen, Hans,Heiker, Fred R.
-
p. 2180 - 2203
(2007/10/02)
-