- Nitrenium ion-mediated alkene bis-cyclofunctionalization: Total synthesis of (-)-swainsonine
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Chemical equations presented. The total synthesis of (-)-swainsonine from 2,3-O-isopropylidene-d-erythrose in 12 steps and an overall yield of 28% is reported. The pivotal transformation in our route to this indolizidine alkaloid is the formation of the pyrrolidine ring and C-8a/8 stereodiad through the diastereoselective, bis-cyclofunctionalization of an γ,ss-unsaturated O-alkyl hydroxamate. This transformation is believed to proceed via the intramolecular capture of an N-acyl-N-alkoxyaziridinium ion generated by the diastereoselective addition of a singlet acylnitrenium ion to the pendant alkene.
- Wardrop, Duncan J.,Bowen, Edward G.
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Read Online
- Concise and divergent total synthesis of swainsonine, 7-alkyl swainsonines, and 2,8a-diepilentiginosine via a chiral heterocyclic enaminoester intermediate
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The concise and divergent total syntheses of (-)-swainsonine, (-)-7-alkyl swainsonines, and (-)-2,8a-diepilentiginosine from a common chiral heterocyclic enaminoester intermediate in five-step sequences are presented. The highly efficient annulation reaction of the chiral heterocyclic enaminoester with various α,β-unsaturated carboxylates, and a straightforward carboxy inversion constituted the key features of the synthetic pathway. This work provides an example for divergent synthesis of different natural and unnatural polyhydroxylated indolizidines from a readily available platform.
- Shi, Gao-Feng,Li, Jia-Qi,Jiang, Xiao-Ping,Cheng, Ying
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- Diisopropyl tartrate-modified (E)-γ-[(menthofuryl)dimethylsilyl]-allyl boronate, an improved chiral reagent for the anti α-hydroxyallylation of aldehydes. Application to the enantioselective synthesis of (-)-swainsonine
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An enantioselective synthesis of anti 1,2-diols via the reactions of aldehydes and the tartrate ester-modified (E)-γ-(menthofurylsilyl)allylboronate 5 has been developed. This methodology is applied to a brief, enantioselective synthesis of (-)-swainsonine.
- Hunt,Roush
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Read Online
- A process for preparing the swainsonine [( -) - Swainsonine] method
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The present invention belongs to the field of chemical synthesis, and relates to a preparation method of (-)-Swainsonine having anti-cancer activity. According to the present invention, the technical route has characteristics of simple operation, simple route and high yield, and the used reagents are the commonly used reagents; and the cost can be significantly reduced, the 10-100 g-scale preparation can be easily prepared in the laboratory, and the method is suitable for large-scale preparation.
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- Epimerization of C5 of an: N -hydroxypyrrolidine in the synthesis of swainsonine related iminosugars
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Epimerization of C5 of an N-hydroxypyrrolidine ring by regioselective oxidation to a nitrone followed by diastereoselective reduction provides a new approach to the synthesis of swainsonine and related compounds. The only protection in the synthesis of the potent mannosidase inhibitor DIM (1,4-dideoxy-1,4-imino-d-mannitol) was the acetonation of d-mannose.
- Qian, Bao-Chen,Kamori, Akiko,Kinami, Kyoko,Kato, Atsushi,Li, Yi-Xian,Fleet, George W. J.,Yu, Chu-Yi
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p. 4488 - 4498
(2016/06/06)
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- Synthesis of polyhydroxylated indolizidines and piperidines from Garner's aldehyde: Total synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine, pentahydroxy indolizidines, (-)-1-deoxynojirimycin, (-)-1-deoxy-altro-nojirimycin, and related diversity
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Diastereoselective and diverse synthesis of polyhydroxylated indolizidines and piperidines have been described, where a common chiral intermediate 2-(hydroxymethyl) piperidine-3-ol is converted into (-)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine, pentahydroxy indolizidines, (-)-1-deoxynojirimycin, (-)-1-deoxy-altro-nojirimycin, and related diversity. The key steps were hydroxy directed intramolecular aminomercuration, Mitsunobu cyclization, and diastereoselective dihydroxylation.
- Singh, Priyanka,Manna, Sudipta Kumar,Panda, Gautam
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p. 1363 - 1374
(2014/02/14)
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- Synthesis of pyrrolidine iminosugars, (-)-lentiginosine, (-)-swainsonine and their 8a-epimers from d-glycals
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Synthesis of pyrrolidine iminosugars has been described from d-glycals via dihydroxylation, oxidative cleavage and double nucleophilic displacement as the key steps. The pyrrolidines obtained have been utilized for the synthesis of important bicyclic iminosugars, viz. (-)-lentiginosine and (-)-swainsonine and their 8a-epimers, which are known to be glycosidase inhibitors.
- Ansari, Alafia A.,Vankar
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p. 12555 - 12567
(2014/03/21)
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- Intramolecular 5-endo-trig aminopalladation of β-hydroxy-γ- alkenylamine: Efficient route to a pyrrolidine ring and its application for the synthesis of (-)-8,8a-di-epi-swainsonine
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The intramolecular aminopalladation reaction of l-serine derived β-hydroxy-γ-alkenylamines undergoes 5-endo-trig cyclization to furnish pyrrolidine rings in high yields. The pyrrolidines thus obtained were used in the synthesis of (-)-8,8a-di-epi-swainsonine, a specific and competitive inhibitor (Ki value 2 × 10-6 M) of lysosomal α-mannosidases.
- Singh, Priyanka,Panda, Gautam
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p. 2161 - 2166
(2014/01/06)
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- Asymmetric formal synthesis of (-)-swainsonine by a highly regioselective and diastereoselective allylic amination using chlorosulfonyl isocyanate
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A concise asymmetric formal synthesis of (-)-swainsonine from readily available D-erythronolactone is described. The key steps include a highly diastereoselective amination of a chiral benzylic ether, which occurs with the retention of stereochemistry using chlorosulfonyl isocyanate, and a palladium-catalyzed decarboxylative N-allylation of an allyl carbamate. Copyright
- Li, Qing Ri,Dong, Guang Ri,Park, Sook Jin,Hong, Yong Rae,Kim, In Su,Jung, Young Hoon
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p. 4427 - 4433
(2013/07/26)
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- A flexible enantioselective approach to 3,4-dihydroxyprolinol derivatives by SmI2-mediated reductive coupling of chiral nitrone with ketones/aldehydes
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A flexible enantioselective approach to polyhydroxylated prolinol derivatives was described, which is based on the samarium diiodide-mediated reductive coupling of the chiral nitrone (3S,4R)-8, derived from d-isoascorbic acid with aldehydes/ketones. Thereby, polyhydroxyprolinol derivatives 9a-e and 9h-j were obtained from aromatic ketones and aliphatic aldehydes in good to excellent yields of 65-91%. These reductive hydroxyalkylations are highly diastereoselective in establishing the C-4 stereogenic center. By this way, the asymmetric syntheses of (-)-8a-epi-swainsonine (4) and (-)-8,8a-di-epi- swainsonine (5) have been achieved.
- Zhang, Hong-Kui,Xu, Shou-Qiang,Zhuang, Jia-Jia,Ye, Jian-Liang,Huang, Pei-Qiang
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p. 6656 - 6664
(2012/08/29)
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- A facile synthesis of 1,4-dideoxy-1,4-imino-l-ribitol (LRB) and (-)-8a-epi-swainsonine from d-glutamic acid
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A facile synthesis of (-)-8a-epi-swainsonine 2 and 1,4-dideoxy-1,4-imino-l- ribitol (LRB) 4 has been achieved by using the versatile building block 3, which was available from cheap d-glutamic acid. The new forming stereogenic center in synthesis of 2 was constructed by highly selective reduction of the ketone 13 with Li(t-BuO)3AlH in THF (dr=95:5).
- Wang, Xiao-Ling,Huang, Wen-Feng,Lei, Xin-Sheng,Wei, Bang-Guo,Lin, Guo-Qiang
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p. 4919 - 4923
(2011/07/31)
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- Asymmetric synthesis of (-)-swainsonine
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(Chemical Equation Presented) We report a new asymmetric synthetic method for (-)-swainsonine utilizing a chiral oxazoline precursor. The key features in this strategy are the diastereoselective oxazoline formation reaction catalyzed by palladium(0), dias
- Tian, Yong-Shou,Joo, Jae-Eun,Kong, Bae-Soo,Pham, Van-Thoai,Lee, Kee-Young,Ham, Won-Hun
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experimental part
p. 3962 - 3965
(2009/10/08)
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- De novo asymmetric syntheses of d-, l- and 8-epi-d-swainsonine
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A highly enantioselective and stereocontrolled approach to d-, l- and 8-epi-d-swainsonine has been developed from achiral furan and γ-butyrolactone. A one-pot hydrogenolysis of both azide and benzyl ether followed by an intramolecular reductive amination has been employed as key step to establish the indolizidine ring system. The absolute stereochemistry was installed by the Noyori reduction and the relative stereochemistry by the use of several highly diastereoselective palladium-catalyzed glycosylation, Luche reduction, dihydroxylation, and palladium-catalyzed azide allylation reactions. This practical approach provide multigram quantities of indolizidine natural product d-swainsonine in 13 steps and 25% overall yield.
- Guo, Haibing,O'Doherty, George A.
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p. 304 - 313
(2008/04/01)
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- De novo asymmetric synthesis of 8a-epi-swainsonine
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(Chemical Equation Presented) An enantioselective and diastereocontrolled approach to 8a-epi-D-swainsonine has been developed from achiral furfural. The key step to this synthesis was a one-pot procedure for the hydrogenolytic removal of two protecting groups and two intramolecular reductive amination reactions. The absolute stereochemistry was introduced by asymmetric Noyori reduction of furfuryl ketone. This route relies on diastereoselective palladium-catalyzed glycosylation to install the anomeric bond, and Luche reduction, diastereoselective dihydroxylation to set up the manno- stereochemistry of the indolizidine precursor.
- Abrams, Jason N.,Babu, Ravula Satheesh,Guo, Haibing,Le, Dianna,Le, Jennifer,Osbourn, Joshua M.,O'Doherty, George A.
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p. 1935 - 1940
(2008/09/18)
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- De novo asymmetric synthesis of D- and L-swainsonine
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The enantioselective syntheses of both enantiomers of the indolizidine natural product swainsonine have been achieved in 13 steps from furan. The indolizidine ring system is installed by a one-pot hydrogenolysis of both an azide and an O-Bn group along with an intramolecular reductive amination reaction. The asymmetry of swainsonine was introduced by Noyori reduction of an acylfuran. This route relies upon an Achmatowicz rearrangement, a diastereoselective palladium-catalyzed glycosylation, Luche reduction, and a dihydroxylation reaction.
- Guo, Haibing,O'Doherty, George A.
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p. 1609 - 1612
(2007/10/03)
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- Asymmetric [2 + 2] cycloaddition: Total synthesis of (-)-swainsonine and (+)-6-epicastanospermine
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(Chemical Equation Presented) An asymmetric total synthesis of (-)-swainsonine and (+)-6-epicastanospermine is described from a common intermediate, which is obtained through diastereoselective [2 + 2] cycloaddition of dichloroketene to a chiral enol ether.
- Ceccon, Julien,Greene, Andrew E.,Poisson, Jean-Francois
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p. 4739 - 4742
(2007/10/03)
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- General approach to glycosidase inhibitors. Enantioselective synthesis of deoxymannojirimycin and swainsonine
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(Chemical Equation Presented) Deoxymannojirimycin (2) and swainsonine (4) have been synthesized from each enantiomer of the same bicyclic carbarnate precursor 7. The key intermediate was prepared by a simple and efficient three-step synthesis involving RCM of the diene 8, which in turn is easily accessible in any configuration from enantiomerically enriched 2,3-epoxy-4-penten-1-ol 9.
- Martin, Ruben,Murruzzu, Caterina,Pericas, Miquel A.,Riera, Antoni
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p. 2325 - 2328
(2007/10/03)
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- Asymmetric synthesis of (-)-swainsonine
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This paper describes a new synthesis of (-)-swainsonine via the ring-closing metathesis reaction of a substituted 3-allyl-4-vinyloxazolindin-2- one and subsequent diastereoselective syn-dihydroxylation of the resulting pyrrolo[1,2-c]oxazol-3-one.
- Lindsay, Karl B.,Pyne, Stephen G.
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p. 669 - 672
(2007/10/03)
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- Stereoselective synthesis of polyhydroxylated indolizidines based on pyridinium salt photochemistry and ring rearrangement metathesis
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Ruthenium-catalyzed ring rearrangement metathesis (RRM) reactions of stereochemically diverse, differentially protected 4-N- allylacetamidocyclopenten-3,5-diols, prepared by using pyridinium salt photochemistry, have been explored as part of a program to develop novel routes for the synthesis of polyhydroxylated indolizidines. The RRM reactions, which produce selectively protected 1-acetyl-2-allyl-3-hydroxy-1,2,3,6- tetrahydropyridines, were found to take in high yields and with high levels of regioselectivity. The significance of RRM reactions of 4-N- allylacetamidocyclopenten-3,5-diols in the context of polyhydroxylated indolizidine synthesis is demonstrated by an application to the concise preparation of the potent glycosidase inhibitor, (-)-swainsonine.
- Song, Ling,Duesler, Eileen N.,Mariano, Patrick S.
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p. 7284 - 7293
(2007/10/03)
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- Asymmetric synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine, and (+)-1,2,8-tri-epi-swainsonine
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The asymmetric synthesis of (-)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective cis-dihydroxylation using AD-mix-α. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
- Lindsay, Karl B.,Pyne, Stephen G.
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p. 7774 - 7780
(2007/10/03)
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- A new approach to (-)-swainsonine by ruthenium-catalyzed ring rearrangement
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A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in 40% overall yield starting from the known oxazolidinone 6 is described. Throughout the synthesis, the high efficiency of metal-catalyzed reactions is illustrated. The key step is a new ruthenium-catalyzed metathesis rearrangement reaction. In this ring-closing/ring-opening tandem process, stereocenters are transferred from a ring to the olefinic side chain of the formed heterocycle. The metathesis precursor was obtained by palladium-catalyzed desymmetrization of cyclopentenediol. The synthesis was completed by functionalization of the terminal double bond, cyclization of the second ring, and diastereoselective dihydroxylation.
- Buschmann, Nicole,Rueckert, Anke,Blechert, Siegfried
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p. 4325 - 4329
(2007/10/03)
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- Allylated monosaccharides as precursors in triple reductive amination strategies: Synthesis of castanospermine and swainsonine
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The feasibility of the triple-reductive amination reaction for the synthesis of complex indolizidine frameworks is illustrated by application to the potent glycosidase inhibitors castanospermine and swainsonine. The target compounds were obtained from known carbohydrate precursors in yields of 23 and 14%, over nine and 13 steps, respectively. The iodoetherification reaction of allylated monosaccharides was shown to be a practical reaction for the synthesis of the tricarbonyl precursors for the key triple reductive amination reactions.
- Zhao,Hans,Cheng,Mootoo
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p. 1761 - 1767
(2007/10/03)
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- Stereoselective synthesis of (-)-swainsonine and 1,2-di-epi-swainsonine from y-hy droxy-a, -unsatur ated sulfones
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Efficient and stereodivergent syntheses of (-)-swainsonine and l,2-di-ep/-swainsonine starting from the readily available enantiomerically pure y-hydroxy-a,-unsaturated sulfone (R)-2 are described. The stereoselectivity in the osmium-dihydroxylation step of the unsaturated indolizidines 8 was highly dependent on the substitution at C8. 1,2-di-epj-swainsonine was found to be a good inhibitor of a-D-mannosidase (jack bean). Thieme Stuttgart.
- De Vicente, Lavier,Arrayas, Ram?n G?mez,Canada, Lavier,Carretero, Jüan Carlos
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- cis-5-Amino-6-hydroxycyclohexadiene as a chiral building block: An asymmetric synthesis of (-)-swainsonine
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A new asymmetric building block, cis-5-hydroxy-6-aminocyclohexa-1,3- diene in which the double bonds are differentiated as the Diels-Alder adduct with anthracene, is available in an enantiomerically pure form in three or four steps from anthracence and benzoquinone. The key step is a palladium- catalyzed desymmetrization of a meso-2-en-1,4-diol. It serves as a chiral precursor of the anticancer agent swainsonine. Diastereoselective dihydroxylation dictated by the dihydroanthracence unit sets the four stereogenic centers of swainsonine. The sequence then first creates the pyrrolidine ring followed by the piperidine ring. The effectiveness of the synthesis is evident from the overall yield of 15% for the 15-step protocol.
- Trost,Patterson
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p. 3279 - 3284
(2007/10/03)
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- Stereocontrolled Synthesis of trans-3-Hydroxypipecolic Acids and Application to (-)-Swainsonine
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The enantioselective synthesis of both enantiomers of trans-3-hydroxypipecolic acid are described from a prochiral starting material: the methyl 3-oxo-7-methyloct-6-enoate.The stereocenters of the piperidine ring are created by enantioselective hydrogenation of the β-ketoester and by diastereoselective electrophilic amination of the β-hydroxyester enolate. (2R,3R)-3-Hydroxypipecolic acid methyl ester is the precursor for the synthesis of (-)-swainsonine. - Keywords: piperidine; indolizidine; chiral ruthenium complex; electrophilic amination.
- Ferreira, Franck,Greck, Christine,Genet, Jean Pierre
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p. 615 - 622
(2007/10/03)
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- DERIVATIVES OF SWAINSONINE, PROCESSES FOR THEIR PREPARATION AND THEIR USE AS THERAPEUTIC AGENTS
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The invention relates to novel mannosidase inhibitors, processes for their preparation and their use as therapeutic agents. The invention also relates to pharmaceutical compositions containing the compounds and their use as therapeutics
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- An enantiocontrolled synthesis of (-)-Swainsonine
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(-)-Swainsonine 1, first isolated from the fungus Rhizoctonia leguminicola, has been sythesized enantioseletively. The key step was the stereoselective iodoamination of trichloro- acetimidate derived from (Z)- olefinic allylic alcohol 7.
- Kang, Sung Ho,Kim, Geun Tae
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p. 5049 - 5052
(2007/10/02)
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- Process for the preparation of immunostimulating swainsonine analogs
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Disclosed are immunostimulating swainsonine analogs and methods of synthesizing same.
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- New Chiral Route to (-)-Swainsonine via an Aqueous Acylnitroso Cycloaddition Approach
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A new noncarbohydrate-based enantioselective approach to (-)-swainsonine (1) is described, in which the aqueous intramolecular Diels-Alder reaction of a chiral acylnitroso diene has been employed as a key reaction.The intramolecular cycloaddition of the chiral hydroxamic acid 9, available from D-malic acid in 10 steps, with Pr4NIO4 was conducted under the conventional nonaqueous conditions using CHCl3 as a solvent, whereupon intermediacy acylnitroso compound 10 cyclized spontaneously to give the trans- and cis-1,2-oxazinolactams 11 and 12 with a low diastereoselection af 1.3:1 in 76percent combined yield.When the corresponding reaction was performed in water, it led to significant enhancements of trans selectivity of 4.1:1 as well as combined yield (89percent).The trans adduct 11 was subjected to reductive N-O bond cleavage followed by diastereoselective hydroxylation with OsO4 to provide the 1,2-glycol 21, which was then converted to the amino alcohol 25.Intramolecular cyclodehydration of 25 with CBr4/PPh3/Et3N and subsequent deprotection furnished (-)-swainsonine (1).
- Naruse, Masaichi,Aoyagi, Sakae,Kibayashi, Chihiro
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p. 1358 - 1364
(2007/10/02)
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- An Acylnitroso Cycloaddition Approach to the Synthesis of Highly Oxygenated Indolizidine Alkaloids
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A synthetic approach to the synthesis of highly oxygenated indolizidine alkaloids is described.A key feature of the approach is intramolecular cycloaddition between an acylnitroso dienophile and a tethered diene moiety, followed by ring contraction of the 1,2-oxazine so formed to a pyrrolidine.The requisite intermediates were prepared in optically pure form from L-glutamic acid.
- Keck, Gary E.,Romer, Duane R.
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p. 6083 - 6089
(2007/10/02)
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- Synthesis of (-) swainsonine and intermediate compounds employed in such synthesis
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(-)-Swainsonine is prepared by the steps of first reacting a compound having the formula: STR1 wherein each R2 is lower alkyl, with (4-carbalkoxybutyl) triphenylphosphonium bromide in a strong base to obtain an alcohol having the formula: STR2 wherein R2 is as defined above and R is C1 -C8 alkyl; the alcohol is then reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride or benzenesulfonyl chloride in the presence of a tertiary amine to obtain the corresponding sulfonate. Heating the sulfonate with an azide in an organic solvent yields an imine having the formula: STR3 wherein R2 and R are ad defined above. Treating the imine with an inorganic base, in aqueous alcohol provides upon acidification, the corresponding acid. Heating the acid at reflux temperature in organic solvent, yields an enamide having the formula: STR4 wherein R2 is as defined above. Treating the enamide with diborane followed by reaction with hydrogen peroxide provides a protected swainsonine having the formula: STR5 which upon acid hydrolysis gives swainsonine.
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- Enantiomerically pure polyhydroxylated acyliminium ions. Synthesis of the glycosidase inhibitors (-)-swainsonine and (+)-castanospermine
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Hydroxylactams, which are useful precursors of acyl iminium ions for cationic cyclization, are most often prepared by hydride reduction of imides. This procedure is not directly applicable, however, to the enantioselective preparation of any highly substituted hydroxy lactam that would be derived from a meso imide, since such a reduction with the usual achiral agents must produce a racemic product. Two enantioselective methods of preparing representative examples of this type of substituted hydroxylactam have therefore been explored. Reduction of a meso imide with a number of enantiomerically pure chiral reducing agents has been found to give up to 56% ee of the corresponding hydroxylactam. Much higher levels of enantiomeric purity are readily obtainable by direct synthesis from monosaccharide lactones derived from either ribose or lyxose, affording either enantiomeric series of hydroxy lactams, (+)-9α, 14-16, and (-)-9α, 20-23, respectively. One such hydroxylactam, 23 has been converted into the mannosidase inhibitor (-)-swainsonine via a synthetic route that features a novel multiple reduction of a vinylogous N-acylurethane to establish the correct ring juncture stereochemistry. Extension of the monosaccharide strategy to the enantioselective synthesis of six-membered-ring hydroxylactams also allows a facile preparation of 29, leading to the glucosidase inhibitor (+)-castanospermine and the new indolizidine alkaloid 1,8a-diepicauistanospermine.
- Miller, Scott A.,Chamberlin, A. Richard
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p. 8100 - 8112
(2007/10/02)
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- The intramolecular cycloaddition of azides with ω-chloroalkenes. A facile route to (-)-swainsonine and other indolizidine alkaloids
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A potentially general route to the 1-azabicyclo[n.m.0]alkane skeleton of various alkaloids is embodied in the intramolecular 1,3-dipolar cycloaddition of aliphatic azides with ω-chloroalkenes. Cycloaddition is followed by rearrangement and intramolecular N-alkylation, affording bicyclic iminium ions 1 in one operation. The application of this method to the synthesis of (±)-δ-coniceine 6, (1S,2R,8aR)-indolizidine-1,2-diol 13 and (-)-swainsonine 15 is described.
- Pearson,Lin
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p. 7571 - 7574
(2007/10/02)
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- SYNTHESIS OF THE MANNOSIDASE INHIBITORS SWAINSONINE AND 1,4-DIDEOXY-1,4-IMINO-D-MANNITOL AND OF THE RING CONTRACTED SWAINSONINES, (1S, 2R, 7R, 7aR)-1,2,7-TRIHYDROXYPYRROLIZIDINE AND (1S, 2R, 7S, 7aR)-1,2,7-TRIHYDROXYPYRROLIZIDINE.
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4,5-Anhydro-1-azido-1-deoxy-2,3-O-isopropylidene-D-talitol is a divergent intermediate for the efficient and practical syntheses of 1,4-dideoxy-1,4-imino-D-mannitol, swainsonine and of the ring contracted swainsonines, (1S, 2R, 7R, 7aR)-1,2,7-trihydroxypyrrolizidine and (1S, 2R, 7S, 7aR)-1,2,7-trihydroxypyrrolizidine.The effect on glycosidases of the ring contracted swainsonines is reported.
- Carpenter, Neil M.,Fleet, George W. J.,Bello, Isabelle Cenci di,Winchester, Bryan,Fellows, Linda E.,Nash, Robert J.
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p. 7261 - 7264
(2007/10/02)
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- A Short, Enantioselective Synthesis of (-)-Swainsonine
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A practical, enantioselective synthesis of (-)-swainsonine (1) has been achieved in seven steps from 2,3-O-isopropylidene-D-erythorose (6).The key step involves the construction of the bicyclic imine 4 by an intramolecular 1,3 dipolar cycloaddition of azide 5.This study highlights the synthetic utility of the intramolecular 1,3 dipolar cycloaddition of the unactivated olefinic azides in natural product synthesis.
- Bennett, Richard B.,Choi, Jong-Ryoo,Montgomery, Walter D.,Cha, Jin K.
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p. 2580 - 2582
(2007/10/02)
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- SYNTHESIS OF THE α-MANNOSIDASE INHIBITORS SWAINSONINE AND 1,4-DIDEOXY-1,4-IMINO-D-MANNITOL FROM MANNOSE
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4-azido-4-deoxy-2,3-O-isopropylidene-α-D-mannopyranoside is a key intermediate in the syntheses of the α-mannosidase inhibitors, swainsonine and 1,4-dideoxy-1,4-imino-D-mannitol, and of the α-galactosidase inhibitor 1,4-dideoxy-1,4-imino-D-lyxitol, from mannose.
- Bashyal, Bharat P.,Fleet, George W. J.,Gough, Max J.,Smith, Paul W.
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p. 3083 - 3094
(2007/10/02)
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- A NOVEL SKELETAL REARRANGEMENT OF AN INDOLIZIDINE ALKALOID, SVAINSONINE VIA AN AZIRIDINIUM INTERMEDIATE
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Nucleophilic displacement reactions of mesylate 3, derived from swainsonine (1), gave the rearrangement products 5 along with the swainsonine-type products 6 via an aziridinium intermediate 4.
- Setoi, Hiroyuki,Takeno, Hidekazu,Hashimoto, Masashi
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p. 1261 - 1264
(2007/10/02)
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- Synthesis of (-)-8a-epi-Swainsonine, (1S,2R,8R,8aS) -Octahydro-1,2,8-indolizinetriol
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The title compound, one of the stereoisomers of physiologically interesting indolysidine alkaloid swainsonine, has been synthesized from the known methyl 3-azido-4,6-O-benzylidene-3-deoxy-α-D-altropyranoside.
- Tadano, Kin-ichi,Hotta, Yukinori,Morita, Masahiro,Suami, Tetsuo,Winchester, Bryan,Bello, Isabelle Cenci di
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p. 2105 - 2108
(2007/10/02)
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- Enantioselective Synthesis of Swainsonine, a Trihydroxylated Indolizidine Alkaloid
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A total synthesis of (-)-swainsonine in 21 steps and 6.6percent overall yield starting from trans-1,4-dichloro-2-butene and N-benzyl-p-toluenesulfonamide is described.The synthesis employs the methodology of the Masamune/Sharpless approach to polyhydroxylated natural products.
- Adams, Curtis E.,Walker, Frederick J.,Sharpless, K. Barry
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p. 420 - 422
(2007/10/02)
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- TOTAL SYNTHESIS OF (-)-SWAINSONINE, AN α-D-MANNOSIDASE INHIBITOR ISOLATED FROM Swainsona canescens
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A newly isolated alkaloidal toxin, (-)-swainsonine , which exhibits an α-D-mannosidase inhibitory activity, has been synthesised stereoselectively in 15 steps starting from methyl 3-acetamido-2,4,6-tri-O-acetyl-3-deoxy-α-D-mannopyranoside.
- Suami, Tetsuo,Tadano, Kin-Ichi,Iimura, Youichi
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- Enantiospecific Total Synthesis of (-)-Swainsonine: New Aplications of Sodium Borohydride Reduction
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A short, enantiospecific synthesis of (-)-swainsonine (1) from D-mannose has been achieved by a route involving, as a key step, a double cyclization of 4c.The synthesis takes adventage of new features of sodium borohydride for reducing conjugated esters and lactams.
- Setoi, Hiroyuki,Takeno, Hidekazu,Hashimoto, Masashi
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p. 3948 - 3950
(2007/10/02)
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- SYNTHESIS OF THE INDOLIZIDINE ALKALOID SWAINSONINE FROM D-GLUCOSE
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Since the stereochemistry of the alkaloid exactly matches that of 3-amino-3-deoxy-D-mannose, he latter compound is an ideal chiron for the synthesis of the former.Selective tosylation of methyl 3-benzyloxycabonylamino-3-deoxy-α-D-mannopyranoside, followed by removal of the benzyloxycarbonyl group and cyclisation, afforded the 3,6-imine which was converted into its benzyloxycarbonyl derivative.Hydrolysis of the glycosidic group the afforded 3,6-benzyloxycarbolylimino-3,6-dideoxy-D-mannose.The attempted addition of a C2 unit at C-1 by the Wittig or the Wadsworth-Emmons-Horner reaction either failed to give the required product or was followed by Michael addition of one of the hydroxyl groups to the newly formed double-bond. 2,4,5-Tri-O-acetyl-3,6-benzyloxycarbonylimino-3,6-dideoxy-aldehydo-D-mannose was prepared via the diethyl dithioacetal and condensed with ethoxycarbonylmethylenetriphenylphosphorane to give the Wittig adduct in good yield, which, on catalytic reduction, underwent hydrogenation of the double bond, loss of the benzyloxycarbonyl group, and attack of the released amino group on either the terminal ethoxycarbonyl group or the 2-O-acetyl group to give a mixture of the required cyclic lactam and the N-acetyl derivative.Reduction of the lactam with the borane-dimethyl sulfide complex afforded swanisonine triacetate, from which the parent alkaloid was obtained.
- Ali, Mezher,Hough, Leslie,Richardson, Anthony C.
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p. 224 - 240
(2007/10/02)
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