Stereoselective Synthesis of All Stereoisomers of Orthogonally Protected Cyclobutane-1,2-diamine and Some Chemoselective Transformations

Sans, Marta; Illa, Ona; Ortuño, Rosa M.

doi:10.1021/ol300689e

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…Ligands H4(L1), H4(L2), and H4(L3) were synthesized according to Scheme 1, starting from chiral and orthogonally protected (1S,2S)-1,2-cyclobutanediamine, 1, which was previously described. [10] Scheme 1. Synthesis of Ligands H4cbdta, H4cbddapa, and H4cbddadpa (H4(L1),…”

Section: Resultsmentioning

confidence: 99%

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

et al. 2019

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In an effort of exploring novel ligand scaffolds for stable and inert lanthanide complexation in MRI contrast agent research, three chiral ligands containing a highly rigid (1S,2S)-1,2-cyclobutanediamine spacer and different number of acetate and picolinate groups have been efficiently synthesized. Potentiometric studies show comparable thermodynamic stability for the Gd 3+ complexes formed with either the octadentate (L3) 4 bearing two acetate or two picolinate groups or the heptadentate (L2) 4 analogue bearing one picolinate and three acetate groups (logKGdL = 17.41 and 18.00 for [Gd(L2)]  and [Gd(L3)]  respectively). In contrast, their dissociation kinetics reveals to be very different: the monohydrated [Gd(L3)]  is considerably more labile, as a result of the significant kinetic activity of the protonated picolinate function, as compared to the bishydrated [Gd(L2)] . This constitutes an uncommon example in which lowering ligand denticity results in a remarkable increase in kinetic inertness. Another interesting observation is that the rigid ligand backbone induces an unusually strong contribution of the spontaneous dissociation to the overall decomplexation process. Thanks to the presence of two inner sphere water molecules, [Gd(L2)]  is endowed with high relaxivity (r1 = 7.9 mM-1 s-1 at 20 MHz, 25°C) which is retained in the presence of large excess of endogenous anions, excluding ternary complex formation. The water exchange rate is similar for [Gd(L3)]  and [Gd(L2)]  while it is one order of magnitude higher for the trishydrated tetraacetate analogue [Gd(L1)]  (kex 298 = 8.1, 10 and 127×10 6 s-1 , respectively). A structural analysis via DFT calculations suggests that the large bite angle imposed by the rigid (1S,2S)-1,2-cyclobutanediamine spacer could allow the design of ligands based on this scaffold with suitable properties for the coordination of larger metal ions with biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

et al. 2019

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“…Finally transformations such as reduction of aminocyclobutenes [193] or Curtius rearrangement of cyclobutyl half-esters [194] were employed to access DA aminocyclobutanes. However as they do not imply the construction of the four-membered ring, we will not describe them further in this thesis.…”

Section: Synthesismentioning

confidence: 99%

“…The mixture was heated twice at 200°C for 30 s with 10 s pre-stirring, using Biotage Initiator 2.0 microwave reactor. 194 5 Following a modified procedure [6], a solution of dibenzyl 2-diazomalonate (253) (2.0 g, 6.5 mmol, 1.10 equiv) in dichloromethane (12.0 mL) was added dropwise over 5 min to a solution of 2-vinylisoindoline-1,3-dione (183) Dimethyl 2-(1,3-dioxoisoindolin-2-yl)cyclopropane-1,1-dicarboxylate (223) (10 mg, 0.034 mmol, 1 equiv) and indole (0.051 mmol, 1.5 equiv) were dissolved in solvent (0.20 mL) and added to the Lewis acid (3.4 µmol, 0.1 equiv) in a sealed tube closed with a septum. The solid was filtrated over a filter paper, washed with water (15 mL) and hexane (20 mL) Following a modified procedure [6], a solution of dimethyl 2-diazomalonate (199) (0.20 g, 1.3 mmol, 1.5 equiv) in dichloromethane (2.0 mL) was added 192 5 Following a modified procedure [6], a solution of dimethyl 2-diazomalonate (199) (w).…”

Section: Friedel-craft Alkylation With Indolesmentioning

confidence: 99%

Synthesis and Reactivity of Donor-Acceptor Substituted Aminocyclopropanes and Aminocyclobutanes

Nanteuil¹

2016

Springer Theses

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“…From these compounds, we synthesized peptides with properties as foldamers in solution [16,17,18] and/or LMWG [19,20] as well as neuropeptide Y (NPY) analogues [21]. Amino alcohols [22] and diamines [22,23] have also been prepared, some of them with application in organocatalysis [22,23]. The 1,3-diamine motif is found in natural products and also in the structure of ligands for metal catalysts.…”

Section: Introductionmentioning

confidence: 99%

Cyclobutane-Containing Scaffolds as Useful Intermediates in the Stereoselective Synthesis of Suitable Candidates for Biomedical Purposes: Surfactants, Gelators and Metal Cation Ligands

Illa

Serra

Ardiaca

et al. 2019

IJMS

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Efficient and versatile synthetic methodologies are reported for the preparation of products that are suitable candidates to be used as surfactants, gelators for hydroxylic solvents or metal cation ligands, with potential use in several fields including biomedical applications. The common structural feature of all the synthesized products is the presence of a cis or trans-1,2- or cis-1,3-difunctionalized cyclobutane ring. In the two first cases, the key intermediates including enantiomerically pure 1,3-diamines and 1,3-amino alcohols have been prepared from β-amino acid derivatives obtained, in turn, from a chiral half-ester. This compound is also precursor of γ-amino esters. Furthermore, two kind of polydentate ligands have also been synthesized from a symmetric 1,5-diamine obtained from norpinic acid, which was easily prepared from commercial verbenone.

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Stereoselective Synthesis of All Stereoisomers of Orthogonally Protected Cyclobutane-1,2-diamine and Some Chemoselective Transformations

Cited by 21 publications

References 25 publications

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

Synthesis and Reactivity of Donor-Acceptor Substituted Aminocyclopropanes and Aminocyclobutanes

Cyclobutane-Containing Scaffolds as Useful Intermediates in the Stereoselective Synthesis of Suitable Candidates for Biomedical Purposes: Surfactants, Gelators and Metal Cation Ligands

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