231618-87-4

Upstream product

• 1105054-60-1 (2R,3R,4R,5R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-5-vinylpyrrolidin-1-ol 
• 537030-19-6 (2R,3R,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-3,4-dihydro-2H-pyrrole 1-oxide 
• 173142-28-4 (1'R,2R,3S,4R,5R)-3,4-bis(benzyloxy)-5-<(benzyloxy)methyl>-2-<1',2'-dihydroxyethyl>pyrrolidine 
• 231619-09-3 (2R,3S,4S,5R,6R)-6-azido-2,3-epoxy-4,5,7-tris(benzyloxy)-2(E)-hepten-1-ol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 231618-86-3 (1''R,2R,3R,4R,5R)-N-butyloxycarbonyl-3,4-bis(benzyloxy)-5-<(benzyloxy)methyl>-2-<1,2-dihydroxyethyl>pyrrolidine 

Downstream Products

• 1450833-94-9 C₃₉H₄₅NO₆ 
• 160925-99-5 C₃₄H₃₇NO₄ 
• 1450833-97-2 C₄₆H₄₈N₂O₆ 
• 1450833-84-7 C₃₈H₄₆N₂O₄ 
• 1450834-03-3 C₅₃H₅₆N₂O₅ 
• 1450834-05-5 C₅₉H₆₂N₂O₅ 
• 1450833-06-3 N-(4-((2R,3R,4R,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl) pyrrolidin-1-yl)butyl)-3,3,3-triphenylpropanamide 
• 301310-42-9 (1R,2R,3R,7S,7aR)-1,2-dibenzyloxy-3-benzyloxymethyl-7-hydroxy-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine 
• 137741-26-5 (1R,2R,3R,7R,7aR)-1,2-bs(benzyloxy)-3-[(benzyloxy)methyl]hexahydro-1H-pyrrolizin-7-ol 

Relevant academic research and scientific papers

Synthesis of novel polyhydroxylated pyrrolidine-triazole/-isoxazole hybrid molecules

A straightforward synthesis of novel, 2-heterocyclyl polyhydroxylated pyrrolidines is described. Stereocontrolled additions of nucleophiles to cyclic nitrones generated the corresponding 2,3-trans adducts, allowing the synthesis of the corresponding pyrrolidines via key intermediates bearing an alkyne and a nitrile oxide. Three hybrid systems, including a pyrrolidine with two isoxazoles and one triazole, are efficiently prepared via 1,3-dipolar cycloaddition. Biological testing of the product alkaloids showed that subtle structural variations have drastic effects on their inhibitory activities against glucosidases. This journal is

Synthesis and inhibition study of bicyclic iminosugar-based alkaloids, scaffolds, and libraries towards glucosidase

A small library of bicyclic iminosugar-based alkaloids and scaffolds possessing a polyhydroxylated pyrrolidine and a varied ring skeleton have been synthesized. Through rapid diversification of the scaffold via an amide coupling with random carboxylic acids, structurally diverse bicyclic iminosugar-based libraries were prepared with substituent diversity, core diversity, and configurational diversity. This discovery process allowed us to efficiently sieve out potent and specific glycosidase inhibitors, and a bicyclic, conformationally restricted iminosugar was demonstrated to be more potent than the monocyclic ones in this study. The most potent and selective inhibitor discovered was found to have a Ki value of 71 nM against α-glucosidase.

Rapid modifications of N-substitution in iminosugars: Development of new β-glucocerebrosidase inhibitors and pharmacological chaperones for Gaucher disease

The rapid discovery of β-glucocerebrosidase (GCase) inhibitors and pharmacological chaperones for Gaucher disease is described. The N-aminobutyl DNJ-based iminosugar was synthesized and conjugating with a variety of carboxylic acids to generate a N-diversely substituted iminosugar-based library. Several members of this library were found to be nanomolar-range inhibitors of GCase; the inhibition constant Ki of the most potent was found to be 71 nM. Although these new molecules showed reasonable chaperoning activity (1.5- to 1.9-fold) in the N370S fibroblast of Gaucher patient-derived cell line, this was accompanies by a concomitant decrease in the cellular α-glucosidase activity, which might limit their further therapeutic potential. Next, newly developed N-substituents were assembled with pyrrolidine-based scaffolds to generate new molecules for further evaluation. The new 2,5-dideoxy-2,5-imino-d- mannitol (DMDP)-based iminosugar 22 was found to exhibit a satisfactory chaperoning activity to enhance GCase activity by 2.2-fold in Gaucher N370S cell line, without impairment of cellular α-glucosidase activity.

A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP

A practical method for the synthesis of five-membered iminocyclitols, pyrrolidine alkaloids bearing multiple hydroxyl substituents, has been developed. All of the eight key intermediates, enantiopure tri-O-benzyl cyclic nitrones, are prepared from four cheap, readily available d-aldopentoses. The nucleophilic addition of cyclic nitrones with vinyl magnesium chloride and TMSCN shows high 2,3-trans stereoselectivity. To construct the 2,3-cis configurations, inversion of the C-2 nitrile group is achieved via an elimination-reduction sequence. Using this approach, five isomers of DMDP and six isomers of ADMDP are prepared efficiently. In the biological evaluation, iminocyclitol 27 is a new and potent inhibitor against β-hexosaminidase with an IC50 value of 0.2 μM.

Iminocyclitol inhibitors of hexoaminidase and glycosidase

Designed iminocylitols that have potent inhibition activity with respect to hexominidases and glycosides are disclosed.

A versatile synthetic strategy for the preparation and discovery of new iminocyclitols as inhibitors of glycosidases

A series of iminocyclitols was prepared using a versatile synthetic strategy, and their inhibition of glycosidases was evaluated using capillary electrophoresis. The study has demonstrated that remarkable specificities in enzyme inhibition can be achieved with small modifications on the aglycon side chain and the ring nitrogen. Among the compounds synthesized, (2R,3R,4R,5R)-N-methyl-2(acetamidomethyl)-3,4-dihydroxy-5- (hydroxymethyl)pyrrolidine was found to be very potent against β-N- acetylhexosaminidase P with the K(i) value of 80 nM.