138258-69-2Relevant articles and documents
Structural essentials for β-: N -acetylhexosaminidase inhibition by amides of prolines, pipecolic and azetidine carboxylic acids
Glawar,Martínez,Ayers,Hollas,Ngo,Nakagawa,Kato,Butters,Fleet,Jenkinson
, p. 10371 - 10385 (2016/11/18)
This paper explores the computer modelling aided design and synthesis of β-N-acetylhexosaminidase inhibitors along with their applicability to human disease treatment through biological evaluation in both an enzymatic and cellular setting. We investigated the importance of individual stereocenters, variations in structure-activity relationships along with factors influencing cell penetration. To achieve these goals we modified nitrogen heterocycles in terms of ring size, side chains present and ring nitrogen derivatization. By reducing the inhibitor interactions with the active site down to the essentials we were able to determine that besides the established 2S,3R trans-relationship, the presence and stereochemistry of the CH2OH side chain is of crucial importance for activity. In terms of cellular penetration, N-butyl side chains favour cellar uptake, while hydroxy- and carboxy-group bearing sidechains on the ring nitrogen retarded cellular penetration. Furthermore we show an early proof of principle study that β-N-acetylhexosaminidase inhibitors can be applicable to use in a potential anti-invasive anti-cancer strategy.
Stereoselective synthesis of 3,4-dihydroxylated prolines and prolinols starting from L -tartaric acid
Oba,Koguchi,Nishiyama
, p. 237 - 243 (2014/02/14)
A straightforward and stereoselective synthesis of 3,4-dihydroxyprolines and 3,4-dihydroxyprolinols is described. The key reaction in this synthesis is a protective group-controlled diastereoselective cyanation of a chiral acyliminium intermediate derived from l-tartaric acid. Methanolysis of the obtained cyanolactam gave methyl 3,4-dihydroxypyroglutamate that was converted to 3,4-dihydroxyproline and 3,4-dihydroxyprolinol by reduction of the lactam carbonyl and ester groups in a stepwise manner.
Synthesis of dihydroxylated prolines and iminocyclitols from five-membered endocyclic enecarbamates. Total synthesis of the potent glycosidase inhibitor (2R,3R,4R,5R)-2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP)
Garcia, Ariel Lázaro L.,Correia, Carlos Roque D.
, p. 1553 - 1557 (2007/10/03)
cis- and trans-3,4-Dihydroxylated prolines and the iminocyclitol 1,4-dideoxy-1,4-imino ribitol were synthesized employing a strategy involving the Heck arylation of five-membered endocyclic enecarbamates with aryldiazonium salts followed by oxidative cleavage of the electron-rich aromatic ring. The total synthesis of the potent α- and β-glucosidase inhibitor (2R,3R,4R,5R)-2,5-hydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) was also achieved by the same strategy in ten steps from a chiral five-membered enecarbamate in 12% overall yield.
Efficient synthesis of a new aminoazasugar and dihydroxyprolines from an endocyclic enecarbamate
Pohlit, Adrian M.,Correia, Carlos Roque D.
, p. 2321 - 2325 (2007/10/03)
A novel procedure for the synthesis of trans-2,3-(2-aminomethyl)-cis-3,4-dihydroxypyrrolidine (a new aminoazasugar) and cis-2,3- and trans-2,3-cis-3,4-dihydroxyprolines is presented. Starting from the known endocyclic enecarbamate 1-carbobenzyloxy-2-pyrro
(±)-4-amino-4,5-dideoxyribose, (±)-4-amino-4-deoxyerythrose, and (±)-dihydroxyproline derivatives from N-dienyl-γ-lactams
Behr,Defoin,Mahmood,Streith
, p. 1166 - 1177 (2007/10/02)
Hetero-Diels-Alder cycloaddition of acylnitroso dienophile 4 with the N-(butadienyl)pyrrolidinone derivatives 2a,b led with complete regioselectivity to the oxazine adducts 5a,b. Sequential osmylation, protection of the ensuing glycol, and reduction of th
DIPOLAR CYCLOADDITION REACTIONS OF AZOMETHINE YLIDES FOR THE SYNTHESIS OF POLYHYDROXYPYRROLIDINES AS POTENTIAL ENZYMATIC INHIBITORS
Hassan, Mohamed E.
, p. 7 - 9 (2007/10/02)
Tosyl and benzyl azomethine ylides generated from the corresponding aziridines under thermal and photochemical conditions, were trapped by dipolar cycloaddition reaction with vinylene carbonate.The methoxycarbonyl group in the pyrrolidines obtained was re
Synthesis of (3S,4S)-3,4-dihydroxyprolines from L-tartaric acid
Arakawa,Yoshifuji
, p. 2219 - 2224 (2007/10/02)
Natural (2S,3S,4S)-3,4-dihydroxyproline (1) and the new (2R,3S,4S)-isomer (7) have been synthesized from L-tartaric acid via cyanosilylation of the cyclic Schiff base.
