Summary.
We present the synthesis of new modular dipeptide mimetics based on diazabicycloalkane backbones. These diazabicycloalkanes are ligands for the prostate specific membrane antigen (PSMA), a well known tumor marker. Our previously described synthetic route to enantiomerically pure diazabicycloalkanes is extended to yield polyfunctional diazabicycloalkanes with a modular character using a new ring closing methodology. This, finally, allows us to attach linker moieties to different positions of the diazabicycloalkane scaffold providing conjugation sites to other functional molecules such as markers or cytostatic compounds. Furthermore, successful synthesis of sulphur-containing dipeptide analogues as for example CysXAA- or HCysXAA-mimetics on the basis of diazabicycloalkanes is described.
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L Belvisi L Colombo M Colombo M Di Giacomo L Manzoni B Vodopivec C Scolatico (2001) ArticleTitlePractical stereoselective synthesis of conformationally constrained unnatural proline-based amino acids and peptidomimetics. Tetrahedron 57 6463–6473 Occurrence Handle10.1016/S0040-4020(01)00538-5
R Bloch (1998) ArticleTitleAdditions of organometallic reagents to C:N bonds: reactivity and selectivity. Chem Rev 98 1407–1438 Occurrence Handle10.1021/cr940474e Occurrence Handle11848938
MF Chan BG Raju A Kois JI Varughese KI Varughese VN Balaji (1999) ArticleTitleDesign and synthesis of 1,4-diazabicyclo[4.3.0]nonane peptidomimetic endothelin antagonists. Heterocycles 51 5–8
I Collado J Ezquerra JJ Vaquero C Pedregal (1994) ArticleTitleDiastereoselective functionalization of 5-hydroxy prolinates by tandem Horner-Emmons-Michael reaction. Tetrahedron Lett 35 8037–8040
MP Cooke SuffixJr DL Burman (1982) ArticleTitleCharge-directed conjugate addition reactions in the preparation of substituted methyl ketones. J Org Chem 47 4955–4963 Occurrence Handle10.1021/jo00146a025
CE Grossmith F Senia J Wagner (1999) ArticleTitleSynthesis of novel unsaturated bicyclic lactams by ring-closing metathesis. Synlett 10 1660–1662
L Halab F Gosselin WD Lubell (2000) ArticleTitleDesign, synthesis, and conformational analysis of azacycloalkane amino acids as conformationally constrained probes for mimicry of peptide secondary structures. Biopolymers 55 101–122 Occurrence Handle10.1002/1097-0282(2000)55:2<101::AID-BIP20>3.0.CO;2-O Occurrence Handle11074409
S Hanessian G McNaughton-Smith HG Lombart WD Lubell (1997) ArticleTitleDesign and synthesis of conformationally constrained amino acids as versatile scaffolds and peptide mimetics. Tetrahedron 53 12789–12854 Occurrence Handle10.1016/S0040-4020(97)00298-6
M Harada M Noguchi K Itoh (2003) ArticleTitleTarget molecules in specific immunotherapy against prostate cancer. Int J Clin Oncol 8 193–199 Occurrence Handle10.1007/s10147-003-0332-x Occurrence Handle12955573
M Jaeger K Polborn W Steglich (1995) ArticleTitleOn-site modification of oligopeptides: conversion of seryl into (exo)-2-azabicyclo[2.2.1]hept-5-ene-3-carbonyl residues. Tetrahedron Lett 36 861–864 Occurrence Handle10.1016/0040-4039(94)02432-B
A Jayne Oliver O Wiest P Helquist MJ Miller M Tenniswood (2003) ArticleTitleConformational and SAR analysis of NAALADase and PSMA inhibitors. Bioorg Med Chem 11 4455–4461 Occurrence Handle10.1016/S0968-0896(03)00427-9 Occurrence Handle13129582
BA Klyashchitskii VF Pozdnev EM Beier (1981) ArticleTitleCovalent addition of biologically active agents to polymers. IV. Synthesis of (“affinity”) adsorbents containing L-fucose derivatives. J Gen Chem USSR (engl. transl.) 51 178–182
C Ludwig LG Wistrand (1994) ArticleTitleStereoselective addition of organocopper reagents to cyclic N-acyliminium ions. Acta Chem Scand 48 367–371
W Maison E Arce P Renold R Kennedy DS Kemp (2001) ArticleTitleOptimal N-caps for N-terminal helical templates: effects of changes in H-bonding efficiency and charge. J Amer Chem Soc 123 10245–10254 Occurrence Handle10.1021/ja010812a
W Maison D Küntzer D Grohs (2002) ArticleTitleShort and efficient synthesis of diazabicycloalkane dipeptide mimics. Synlett 11 1795–1798 Occurrence Handle10.1055/s-2002-34901
W Maison DC Grohs AHGP Prenzel (2004) ArticleTitleEfficient synthesis of structurally diverse diazabicycloalkanes: scaffolds for modular dipeptide mimetics with tunable backbone conformations. Eur J Org Chem 7 1527–1543 Occurrence Handle10.1002/ejoc.200300700
P Majer PF Jackson et al. (2003) ArticleTitleSynthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor. J Med Chem 46 1989–1996 Occurrence Handle10.1021/jm020515w Occurrence Handle12723961
M Plehiers S Heilporn D Ekelmans S Leclercq M Sangermano JC Braekman D Daloze (2000) ArticleTitleAn expeditious synthesis of (±)-decahydro-5H-dipyrrolo[1,2-a:1′,2′-c]pyrimidine-5-carbonitrile: a formal synthesis of (±)-tetraponerines-1, −2, −5, and −6. Can J Chem 78 1030–1034 Occurrence Handle10.1139/cjc-78-7-1030
RP Polniaszek SE Belmont R Alvarez (1990) ArticleTitleStereoselective nucleophilic additions to the carbon-nitrogen double bond. 3. Chiral acyliminium ions. J Org Chem 55 215–223 Occurrence Handle10.1021/jo00288a036
D Seebach B Lamatsch R Amstutz AK Beck M Dobler M Egli R Fitzi M Gautschi B Herradon PC Hidber JJ Irwin R Locher M Maestro T Maetzke A Mourino E Pfammatter DA Plattner C Schickli WB Schweitzer P Seiler G Stucky (1992) ArticleTitleStructure and reactivity of five- and six-ring N,N-,N,O-, and O,O-acetals: a lesson in allylic 1,3-strain (A1,3 strain). Helv Chim Acta 75 IssueID3 913–934
M Skrinjar C Nilsson LG Wistrand (1992) ArticleTitleAn efficient synthesis of (+)-anatoxin-a. Tetrahedron: Asym 3 1263–1270 Occurrence Handle10.1016/S0957-4166(00)82084-4
BS Slusher MB Robinson G Tsai ML Simmons SS Richards JT Coyle (1990) ArticleTitleRat brain N-acetylated alpha-linked acidic dipeptidase activity. Purification and immunologic characterization. J Biol Chem 265 21297–21301 Occurrence Handle2250024
WN Speckamp MJ Moolenaar (2000) ArticleTitleNew developments in the chemistry of N-acyliminium ions and related intermediates. Tetrahedron 56 3817–3856 Occurrence Handle10.1016/S0040-4020(00)00159-9
Y St. Denis CE Augelli-Szafran B Bachand KA Berryman J DiMaio AM Doherty JJ Edmunds L Leblond S Levesque LS Narasimhan JR Penvose-Yi JR Rubin M Tarazi PD Winocour MA Siddiqui (1998) ArticleTitlePotent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications. Bioorg Med Chem Lett 8 3193–3198 Occurrence Handle10.1016/S0960-894X(98)00550-2 Occurrence Handle9873701
Y Tong YM Fobian M Wu ND Boyd KD Moeller (2000) ArticleTitleConformationally constrained substance P analogs: The total synthesis of a constrained peptidomimetic for the Phe7–Phe8 region. J Org Chem 65 2484–2493 Occurrence Handle10.1021/jo991649t Occurrence Handle10789461
W Wang J Yang J Ying C Xiong J Zhang C Cai VJ Hruby (2002) ArticleTitleStereoselective synthesis of dipeptide b-turn mimetics: 7-benzyl and 8-phenyl substituted azabicyclo[4.3.0]nonane amino acid esters. J Org Chem 67 6353–6360 Occurrence Handle10.1021/jo0203591 Occurrence Handle12201753
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Grohs, D., Maison, W. Synthesis of modular dipeptide mimetics on the basis of diazabicycloalkanes and derivatives thereof with sulphur containing side chains. Amino Acids 29, 131–138 (2005). https://doi.org/10.1007/s00726-005-0182-0
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DOI: https://doi.org/10.1007/s00726-005-0182-0