85624-09-5Relevant articles and documents
Scale-up synthesis of swainsonine: A potent #-mannosidase II inhibitor
Sharma, Pradeep K.,Shah, Rajan N.,Carver, Jeremy P.
, p. 831 - 836 (2008)
The large-scale synthesis of Swainsonine 1, a potent α-mannosidase II inhibitor, has been achieved with several improvements. The key modifications were (a) performing the Wittig olefination under mild conditions and isolation of the product 4 with modified workup conditions, (b) introduction of the azido group on a large scale under Mitsunobu conditions to produce 12, (c) performing the 1,3-dipolar cycloaddition of an unactivated azide 12 to afford the imino carboxylic ester 7, (d) formation of amide 10 from 7 under mild acidic conditions, and (e) isolation of the final compound 1 as a stable hydrochloride salt. In addition, synthesis of 11 was accomplished from 12 by telescoping the four steps.
(1S,2R,8aS)-1,2-Dihydroxyindolizidine Formation by Rhizoctania leguminicola, the Fungus That Produces Slaframine and Swainsonine
Harris, Thomas M.,Harris, Constance M.,Hill, James E.,Ungemach, Frank S.,Broquist, Harry P.,Wickwire, Brian M.
, p. 3094 - 3098 (1987)
The title diol (6a) has been shown to be a metabolite of Rhizoctonia leguminicola, the fungus that produces two toxic indolizidine alkaloids, swainsonine (1) and slaframine (2).The structure of 6a was established spectroscopically and confirmed by synthesis of both C-8a epimers 6a and 7a.The absolute configuration was inferred from the efficient reutilization of the isolated 6a to form 1.Diol 7a could not be detected among the products of fermentation.It is noteworthy that 6a is probably an intermediate in the biosynthesis of swainsonine although it differs from the alkaloid in being epimeric at the 8a position
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
Singh, Priyanka,Panda, Gautam
, p. 2161 - 2166 (2014/01/06)
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.
A flexible enantioselective approach to 3,4-dihydroxyprolinol derivatives by SmI2-mediated reductive coupling of chiral nitrone with ketones/aldehydes
Zhang, Hong-Kui,Xu, Shou-Qiang,Zhuang, Jia-Jia,Ye, Jian-Liang,Huang, Pei-Qiang
, p. 6656 - 6664 (2012/08/29)
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.
Nitrenium ion-mediated alkene bis-cyclofunctionalization: Total synthesis of (-)-swainsonine
Wardrop, Duncan J.,Bowen, Edward G.
, p. 2376 - 2379 (2011/06/22)
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.
De novo asymmetric syntheses of d-, l- and 8-epi-d-swainsonine
Guo, Haibing,O'Doherty, George A.
, p. 304 - 313 (2008/04/01)
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.
Concise and divergent total synthesis of swainsonine, 7-alkyl swainsonines, and 2,8a-diepilentiginosine via a chiral heterocyclic enaminoester intermediate
Shi, Gao-Feng,Li, Jia-Qi,Jiang, Xiao-Ping,Cheng, Ying
, p. 5005 - 5012 (2008/09/21)
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.
Enantioselective ring expansion of prolinol derivatives. Two formal syntheses of (-)-swainsonine
Déchamps, Ingrid,Pardo, Domingo Gomez,Cossy, Janine
, p. 9082 - 9091 (2008/03/12)
Two enantioselective formal syntheses of (-)-swainsonine have been achieved from l-proline by using an enantioselective ring enlargement of substituted prolinols as the key step. The more efficient synthesis has been achieved in 14 steps with an overall yield of 14%.
De novo asymmetric synthesis of D- and L-swainsonine
Guo, Haibing,O'Doherty, George A.
, p. 1609 - 1612 (2007/10/03)
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.
Asymmetric synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine, and (+)-1,2,8-tri-epi-swainsonine
Lindsay, Karl B.,Pyne, Stephen G.
, p. 7774 - 7780 (2007/10/03)
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.
