121772-98-3Relevant articles and documents
An improved method of oxazolidinone hydrolysis in the asymmetric synthesis of α-alkylprolines
Genin, Michael J.,Baures, Paul W.,Johnson, Rodney L.
, p. 4967 - 4968 (1994)
An improvement in Seebach's method for the synthesis of α-alkylprolines is reported wherein the hydrolysis of the chiral oxazolidinone 2 is performed on a suspension of silica gel in MeOH/H2O. Following hydrolysis, the pure α-alkylproline can be obtained by filtration thereby avoiding a tedious ion exchange purification.
Asymmetric Cα-Alkylation of Proline via Chirality Transfers of Conformationally Restricted Proline Derivative: Application to the Total Synthesis of (-)-Amathaspiramide F
Cho, Hyunkyung,Shin, Jae Eui,Lee, Seokwoo,Jeon, Hongjun,Park, Soojun,Kim, Sanghee
supporting information, p. 6121 - 6125 (2018/10/02)
An efficient strategy for the asymmetric synthesis of Cα-tetrasubstituted proline derivatives from proline has been established. A nitrogen-fused bicyclic system was devised to control the stereodynamics of proline. Through N-quaternizations with allylic electrophiles followed by [2,3]-rearrangements, the bicyclic proline system delivered enantioenriched Cα-tetrasubstituted prolines. This strategy was applied to the concise total synthesis of (-)-amathaspiramide F.
Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain
Lucas, Matthew C.,Weikert, Robert J.,Carter, David S.,Cai, Hai-Ying,Greenhouse, Robert,Iyer, Pravin S.,Lin, Clara J.,Lee, Eun Kyung,Madera, Ann Marie,Moore, Amy,Ozboya, Kerem,Schoenfeld, Ryan C.,Steiner, Sandra,Zhai, Yansheng,Lynch, Stephen M.
scheme or table, p. 5559 - 5566 (2011/02/22)
Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of
Design, synthesis, and in vitro activity of peptidomimetic inhibitors of myeloid differentiation factor 88
Fantò, Nicola,Gallo, Grazia,Ciacci, Andrea,Semproni, Mauro,Vignola, Davide,Quaglia, Marco,Bombardi, Valentina,Mastroianni, Domenico,Zibella, M. Pia,Basile, Giancarlo,Sassano, Marica,Ruggiero, Vito,De Santis, Rita,Carminati, Paolo
, p. 1189 - 1202 (2008/09/20)
We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide AC-RDVLPGT-NH2, belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The a
Allosteric modulation of the dopamine receptor by conformationally constrained type VI β-turn peptidomimetics of Pro-Leu-Gly-NH2
Vartak, Ashish P.,Skoblenick, Kevin,Thomas, Nancy,Mishra, Ram K.,Johnson, Rodney L.
, p. 6725 - 6729 (2008/09/17)
A peptidomimetic of Pro-Leu-Pro-NH2, 7, possessing an indolizidinone type VI β-turn mimic was synthesized via improved high-yielding protocols for the preparation and Cbz protection of α-allylproline. Bicyclic peptidomimetic 7 and spirobicylic
A highly practical RCM approach towards a molecular building kit of spirocyclic reverse turn mimics
Bittermann, Holger,Boeckler, Frank,Einsiedel, Juergen,Gmeiner, Peter
, p. 6315 - 6322 (2008/09/19)
The development of privileged molecular scaffolds efficiently mimicking reverse turn motifs and thus increasing both binding and selectivity and enabling the elucidation of the bio-active conformation of a natural peptide has attracted remarkable interest. The frequent occurrence of proline in various turn patterns initiated the design of proline-based reverse turn mimetics. As a structural hybridization of a highly potent type VI β-turn inducer 1 with saturated spirocyclic lactams 3 efficiently mimicking type II β turns, we developed a versatile synthetic route towards unsaturated spirocyclic lactams of type 2, when Seebach's self-reproduction of chirality methodology was combined with a peptide coupling reaction and Grubbs' ring-closing metathesis. By this means, a variety of model peptides with six- up to nine-membered lactam rings were accessible following a uniform pathway. Introduction of suitably protected templates into solid-phase peptide synthesis gave rise to unsaturated spirocyclic analogues of the naturally occurring neuropeptide neurotensin. Spectroscopic investigations as well as DFT calculations on a high level of theory revealed a remarkable dependence of the reverse-turn inducing potency on the ring size. While the secondary structure of the unsaturated spirocyclic ε-lactam 12 closely agrees with the reference γlactam 3a, the unsaturated δ-lactam 11 serves as an extraordinarily potent β-turn inducer which is even superior to β-lactams of type 3b. The eight-membered unsaturated spirocyclic lactam 13 adopts a conformation almost ideally matching the prerequisites for a canonical type II β turn with the highest stability of the whole series. In contrast, the nine-membered spirolactam 14 represents a scaffold with a high conformational flexibility.
4-Alkyl-2-trichloromethyloxazolidin-5-ones: Valuable precursors to enantiomerically pure C- and N-protected α-alkyl prolines
Wang, Harry,Germanas, Juris P.
, p. 33 - 36 (2007/10/03)
An efficient, economical and enantioselective method for preparation of various mono-and diprotected α-substituted proline derivatives is described. The lithium enolate of known 2-trichloromethyloxazolidin-5-one 3b reacted with electrophiles to furnish th
Design, synthesis, and dopamine receptor modulating activity of spiro bicyclic peptidomimetics of L-prolyl-L-leucyl-glycinamide
Khalil, Ehab M.,Ojala, William H.,Pradhan, Ashish,Nair, Venugopalan D.,Gleason, William B.,Mishra, Ram K.,Johnson, Rodney L.
, p. 628 - 637 (2007/10/03)
In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of
Synthesis, conformational, properties, and antibody recognition of peptides containing β-turn mimetics based on α-alkylproline derivates
Hinds,Welsh,Brennand,Fisher,Glennie,Richards,Turner,Robinson
, p. 1777 - 1789 (2007/10/02)
Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a β-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the β-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic γ-lactam bridge between the α-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-α-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stablized relative to that in the native sequence. For the (S)-α-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the γ-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-α-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.
Design and Synthesis of a Novel Peptide β-Turn Mimetic
Hinds, Mark G.,Richards, Nigel G.J.,Robinson, John A.
, p. 1447 - 1449 (2007/10/02)
The stereospecific synthesis of the novel spirocyclic unit (7), and its use in the construction by solid phase methods, of a conformationally locked analogue of the immunodominant nonapeptide (1) is described.
