- Highly versatile synthesis of polyamines by Ns-strategy on a novel trityl chloride resin
-
A solid-phase synthesis of polyamines on 4-alkoxytrityl chloride resin 5 is described. By alkylation of nitrobenzenesulfonamide 8 with alkyl halide 7 prepared from the resin 5, spermine bound resin 10 was efficiently synthesized. Condensation of 10 and tyrosine derivative followed by deprotection and cleavage from the resin afforded highly pure philanthotoxin-343 (4).
- Kan, Toshiyuki,Kobayashi, Hideki,Fukuyama, Tohru
-
-
Read Online
- Dde - A selective primary amine protecting group: A facile solid phase synthetic approach to polyamine conjugates
-
The ability of the 2-chlorotrityl chloride resin and Dde to act as selective and orthogonal primary amine protecting groups has been utilised in a novel solid phase synthesis of protected symmetrical polyamines from which philanthotoxin-343 and sFTX-3.3 have been synthesized.
- Nash, Ian A.,Bycroft, Barrie W.,Chan, Weng C.
-
-
Read Online
- Side-chain-anchored Nα-Fmoc-Tyr-OPfp for bidirectional solid-phase synthesis
-
(Chemical Equation Presented) A mild resin-immobilization strategy employing a readily prepared trityl bromide resin for anchoring building blocks via a phenol group has been developed. With Nα-Fmoc-Tyr-OPfp as a starter building block, it was possible to prepare asymmetrically substituted hybrids of spider-and wasp-type polyamine toxins using solid-phase peptide synthesis conditions.
- Olsen, Christian A.,Jorgensen, Malene R.,Hansen, Steen H.,Witt, Matthias,Jaroszewski, Jerzy W.,Franzyk, Henrik
-
-
Read Online
- Solid-phase synthesis of symmetrical and unsymmetrical polyamine analogues of philanthotoxins using a Dde-linker
-
The efficient construction of symmetrical and unsymmetrical polyamine analogues of philanthotoxins has been accomplished using the new Dde based linker. The linker allows the selective attachment of primary amines and the resulting linkage displays excell
- Chhabra, Siri Ram,Khan, Azra N.,Bycroft, Barrie W.
-
p. 1095 - 1098
(2007/10/03)
-
- Design, synthesis, and biological evaluation of symmetrically and unsymmetrically substituted methoctramine-related polyamines as muscular nicotinic receptor noncompetitive antagonists
-
The universal template approach to drug design foresees that a polyamine can be modified in such a way to recognize any neurotransmitter receptor. Thus, hybrids of polymethylene tetraamines and philanthotoxins, exemplified by methoctramine (1) and PhTX-343 (2), respectively, were synthesized to produce novel inhibitors of muscular nicotinic acetylcholine receptors. Polyamines 3-25 were synthesized and their biological profiles were evaluated at frog rectus abdominis muscle nicotinic receptors and guinea pig left atria (M2) and ileum longitudinal muscle (M3) muscarinic acetylcholine receptors. All of the compounds, like prototypes 1 and 2, were noncompetitive antagonists of nicotinic receptors while being, like 1, competitive antagonists at muscarinic M2 and M3 receptor subtypes. Interestingly, polyamines bearing a low number of methylenes between the nitrogen atoms, as in 3, 6, and 7, displayed a biological profile similar to that of 2: a noncompetitive antagonism at nicotinic receptors in the 7-25 μM range while not showing any antagonism for muscarinic receptors up to 10 μM. Increasing the number of methylenes separating these nitrogen atoms in methoctramine- related tetraamines resulted in a significant improvement in potency at nicotinic receptors. The most potent tetraamine was 19, bearing a 12 methylene spacer between the nitrogen atoms, which was 12-fold and 250-fold more potent than prototypes 1 and 2, respectively. Tetraamines 9-11, bearing a rather rigid spacer between the nitrogen atoms instead of the very flexible polymethylene chain, displayed a profile similar to that of 1 at nicotinic receptors, whereas a significant decrease in potency was observed at muscarinic M2 receptors. This finding may have relevance in understanding the mode of interaction with these receptors. Similarly, the constrained analogue 12 of methoctramine showed a decrease in potency at nicotinic and muscarinic M2 receptors, revealing that the tricyclic system, which incorporates the 2-methoxybenzylamine moiety of 1, does not represent a good pharmacophore for activity at these sites. A most intriguing finding was the observation that the photolabile tetraamine 22 was more potent than methoctramine at nicotinic receptors and, what is more important, it inhibited a closed state of the receptor.
- Rosini, Michela,Budriesi, Roberta,Bixel, M. Gabriele,Bolognesi, Maria L.,Chiarini, Alberto,Hucho, Ferdinand,Krogsgaard-Larsen, Povl,Mellor, Ian R.,Minarini, Anna,Tumiatti, Vincenzo,Usherwood, Peter N. R.,Melchiorre, Carlo
-
p. 5212 - 5223
(2007/10/03)
-
- Practical synthesis of unsymmetrical polyamine amides
-
Desymmetrisation of readily available symmetrical polyamines is an important first step in the synthesis of many polyamine containing natural products. Likewise in the synthesis of polyamine amides which are potentially useful for gene delivery and as neuroprotectants, based upon channel blocking toxins found in certain wasp and spider venoms. The application of trifluoroacetyl as a protecting group allows unsymmetrical polyamine amides to be easily prepared on a gram scale.
- Blagbrough, Ian S.,Geall, Andrew J.
-
p. 439 - 442
(2007/10/03)
-
- Total Synthesis of Polyamine Amides PhTX-4.3.3 and PhTX-3.4.3: Reductive Alkylation is a Rapid, Practical Route to Philanthotoxins
-
Reductive alkylation allows a rapid and practical entry to the polyamine amide wasp toxin philanthotoxin-4.3.3.Philanthotoxin-3.4.3 has been prepared, in two steps, by the monoacylation of sperimine.These polyamine amides are selective molecular pharmacological tools for cation channels gated by glutamic acid and acetylcholine, and may have potential as a neuroprotective agents.
- Eduardo, Moya,Blagbrough, Ian S.
-
p. 9401 - 9404
(2007/10/02)
-