Indolizidine Analogues Research Articles

Palladium-Catalyzed Double Allylation of Sugar-Imines by Employing Tamaru–Kimura’s Protocol: Access to Unnatural Iminosugars

Conversion of vinyl pyranosylamine and vinyl furanosylamines to 2,6- and 2,5-disubstituted pyrrolidine and piperidine iminosugars, respectively, in one pot was developed using Kimura and Tamaru's procedure, where a Pd salt in the presence of Et2Zn was used for the domino reaction. In this procedure, double allylation, which involves nucleophilic allylation-heterocyclization, took place to give desired nitrogen heterocycles. This strategy was further elaborated to synthesize some unnatural deoxycalystegines, hydroxylated pyrrolidines, piperidines, and indolizidine analogues.

Synthesis of trihydroxylated pyrrolizidine and indolizidine alkaloids based on SmI 2-induced reductive coupling of chiral nitrones with methyl acrylate

Synthesis of trihydroxylated pyrrolizidines, the enantiomer of 2-epihyacinthacine A 2 and indolizidine analogues of the natural alkaloids is reported. The key step of these syntheses is the stereoselective samarium diodide-induced coupling of the chiral nitrone prepared from d-ribose with methyl acrylate. The nitrone derived from d-ribose possessing C2/C3 syn configuration reacted with methyl acrylate in the presence of samarium diiodide in excellent yield and diastereoselectivity, with only the anti-diastereomer being detected.

Total Synthesis of L‐(+)‐Swainsonine and Other Indolizidine Azasugars from D‐Glucose

AbstractA total synthesis of L‐(+)‐swainsonine, a potent and specific inhibitor of naringinase, along with the syntheses of six unnatural indolizidine azasugars are reported by starting from D‐glucose. L‐(+)‐Swainsonine was synthesized in 14 steps in 17 % overall yield. Further, two of the indolizidine analogues were found to be good glycosidase inhibitors at micromolar concentrations. In all of these syntheses, the key step was an intramolecular SN2 reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Synthesis of diastereomerically pure indolizidine and pyrrolizidine analogues from d-pentoses

Partially protected d-pentoses were stereoselectively transformed into the corresponding thiazolidines by the action of cysteamine. Then, a cyclisation with n-BuLi/TsCl or n-Bu 3P/DIAD led to indolizidine or pyrrolizidine analogues. Alternatively, a one-pot preparation of diastereomerically pure indolizidine analogues was realized from 5-O- tosyl- d-pentose derivatives and cysteamine.

Indolizidine derivatives as potential substance P antagonists

Two novel indolizidine analogues, ( 7a) and ( 7b), of the substance P antagonist CP 99,994 have been prepared. Possible conformational factors for their low biological activity are discussed.

Enantiomeric synthesis of polyhydroxylated indolizidine analogues related to castanospermine: 1-deoxy-7-epicastanospermine and 1,7-dideoxy-7-fluorocastanospermine

(6S,7S,8R,8aR)-6,7,8-Trihydroxyindolizidine ( 1) and its (7R)-deoxyfluoro analogue ( 2) was synthesised from 5,8-benzyloxycarbonylimino-5,6,7,8-tetradeoxy-1,2- O-isopropylidene-α-D- gluco-octose ( 3). The key step is an oxidation-reduction sequence. Introduction of a fluoro substituent at C-3 ( 6) was readily effected by displacement of the 3-trifluoromethanesulfonyl (triflate) group with tris-(dimethylamino)-sulfonium-difluorotrimethylsilicate (TASF).