170899-08-8Relevant articles and documents
High Affinity Agonists of the Neuropeptide y (NPY) Y4 Receptor Derived from the C-Terminal Pentapeptide of Human Pancreatic Polypeptide (hPP): Synthesis, Stereochemical Discrimination, and Radiolabeling
Kuhn, Kilian K.,Ertl, Thomas,Dukorn, Stefanie,Keller, Max,Bernhardt, Günther,Reiser, Oliver,Buschauer, Armin
supporting information, p. 6045 - 6058 (2016/07/26)
The diastereomeric mixture of d/l-2,7-diaminooctanedioyl-bis(YRLRY-NH2) (BVD-74D, 2) was described in the literature as a high affinity Y4 receptor agonist. Here we report on the synthesis and pharmacological characterization of the pure diastereomers (2R,7R)- and (2S,7S)-2 and a series of homo- and heterodimeric analogues in which octanedioic acid was used as an achiral linker. To investigate the role of the Arg residues, one or two arginines were replaced by Ala. Moreover, Nω-(6-aminohexylaminocarbonyl)Arg was introduced as an arginine replacement (17). (2R,7R)-2 was superior to (2S,7S)-2 in binding and functional cellular assays and equipotent with 17. [3H]Propionylation of one amino group in the linker of (2R,7R)-2 or at the primary amino group in 17 resulted in high affinity Y4R radioligands ([3H]-(2R,7R)-10, [3H]18) with subnanomolar Kd values.
Stereoselective synthesis of meso-2,6-diaminopimelic acid and its selectively protected derivatives
Gao, Yong,Lane-Bell, Patricia,Vederas, John C.
, p. 2133 - 2143 (2007/10/03)
Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-D-allylglycine (2) and N-(benzyloxycarbonyl)-L-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7- diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-L-vinylglycine moieties, such as N-(benzyloxycarbonyl)-L-glutamate or N-(benzyloxycarbonyl)-L-methionine sulfoxide, gave 12 or 15, both of which produced the α,β-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4- catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-L-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N- (benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol-ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)-copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4- (phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 and 94:6 isometric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N- (benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)-ethyl]sulfonyl]carbomate (34) as a key step.
A practical method for the synthesis of D- or L-α-amino acids by the alkylation of (+)- or (-)-pseudoephedrine glycinamide
Myers, Andrew G.,Gleason, James L.,Yoon, Taeyoung
, p. 8488 - 8489 (2007/10/02)
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