Using ligands derived from D-glucose, dinuclear organotitanium compounds with interesting structural features were synthesized.
A new synthetic route to enantiomerically pure diazabicycloalkanes is reported. Key step of this synthesis is an oxidative cleavage of azabicycloalkene precursors that are synthesized in enantiomerically pure form via aza-Diels-Alder reaction. A range of diazabicycloalkanes with different amino acid side chains have been synthesized and their structure has been elucidated by NMR analysis.Interactions of peptides with receptors and enzymes are important for a great number of physiological processes. In consequence, many peptides serve as lead structures for the development of new pharmaceuticals. However, peptides are not ideal drug candidates due to their low metabolic stability, poor oral availability and rapid excretion. 1 In addition, many small peptides lack selectivity to a certain receptor due to their high conformational flexibility. A common strategy to overcome these problems is the synthesis of conformationally constrained peptide analogues mimicking the bioactive conformation of native peptides at the receptor level. 2 These rigid peptidomimetics should then bind with high affinity and specificity to the receptor and have improved pharmacological profiles. In this context, fused bicyclic systems play an important role in the field of drug discovery. Especially azabicycloalkanes of type II in Figure 1 have been used as tools for rigidifying peptide structures in order to probe conformation-activity relationships. 3 A number of structurally related bicyclic peptide mimics with different ring sizes and heteroatoms have been prepared and incorporated into peptides for example as turn mimics. 3,4 Figure 1 Proposed (I) and known (II) bicyclic dipeptide mimics.In contrast to azabicycloalkanes like II, synthesis and structural properties of diazabicycloalkanes similar to I have rarely been reported so far. 5 In the course of a project directed to the development of rigid bioactive peptidomimetics, that should serve as modular ligands for cancer specific receptors, 6 we became interested in highly functionalized diazabicycloalkane derivatives of the general structure I (Figure 1) in enantiomerically pure form.Although a multistep protocol to a proline derivative similar to structure I is known, 5 a more general synthetic scheme for the synthesis of new bicyclic compounds V (Scheme 1) with various side chains R 1 and R 2 is needed. Such a general route to diazabicycloalkanes V would be especially desirable if both residues R 1 and R 2 were easily converted into a range of different groups mimicking the side chains of a-amino acids and thus offering a route to constrained dipeptide mimics. Since it is important for us to conjugate these dipeptides to fluorescence 7 or radiopharmaceutical markers, 8 we wanted to establish a synthetic route that yields polyfunctional diazabicycloalkanes like V. Within these structures, the aminal OH should be easily converted into a suitable anchor group by standard N-acyliminium chemistry. 9 We have recently demonstrated that azabicycloalkenes III are ideal precursors for subst...
The reaction of methyl‐4,6‐O‐benzylidene‐α‐D‐allopyranoside (α‐MeBAH2) with trichlorocyclopentadienyltitanium [CpTiCl3] and triethylamine in dichloromethane led to the dinuclear complex [(CpTiCl2)2‐μ‐(α‐MeAG)] (1). 1 was characterized by elemental analysis, 1H NMR spectroscopy as well as single crystal X‐ray diffraction.
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