41459-42-1Relevant articles and documents
Chemo-enzymatic synthesis of the exocyclic olefin isomer of thymidine monophosphate
Mondal, Dibyendu,Koehn, Eric M.,Yao, Jiajun,Wiemer, David F.,Kohen, Amnon
, p. 2365 - 2371 (2018)
Exocyclic olefin variants of thymidylate (dTMP) recently have been proposed as reaction intermediates for the thymidyl biosynthesis enzymes found in many pathogenic organisms, yet synthetic reports on these materials are lacking. Here we report two strategies to prepare the exocyclic olefin isomer of dTMP, which is a putative reaction intermediate in pathogenic thymidylate biosynthesis and a novel nucleotide analog. Our most effective strategy involves preserving the existing glyosidic bond of thymidine and manipulating the base to generate the exocyclic methylene moiety. We also report a successful enzymatic deoxyribosylation of a non-aromatic nucleobase isomer of thymine, which provides an additional strategy to access nucleotide analogs with disrupted ring conjugation or with reduced heterocyclic bases. The strategies reported here are straightforward and extendable towards the synthesis of various pyrimidine nucleotide analogs, which could lead to compounds of value in studies of enzyme reaction mechanisms or serve as templates for rational drug design.
Efficient synthesis of methanesulphonate-derived lipid chains for attachment of proteins to lipid membranes
Hicks, Matthew R.,Rullay, Atvinder K.,Pedrido, Rosa,Crout, David H.,Pinheiro, Teresa J. T.
, p. 3726 - 3750 (2008/12/23)
We have developed an easy and flexible synthetic methodology to obtain lipid chains containing methanothiosulfonate terminal groups with the aim to attach them to natural proteins as functional groups. There are many proteins found in nature that are modified by lipids, and this is a key part of their function. For example, the prion protein is attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor, and this protein is thought to be the causative agent in diseases such as bovine spongiform encephalopathy (BSE; "mad cow disease") and the human equivalent Creutzfeldt-Jakob disease. However, production of large amounts of protein in bacteria results in proteins that lack these lipid modifications. The lipid chains containing methanothiosulfonate terminal groups that we have synthesized here can be attached to these proteins through the thiol contained in the side chain of the cysteine residue, which can be incorporated into the protein sequence at the desired position. Copyright Taylor & Francis Group, LLC.
The chemical development and scale-up of sampatrilat
Dunn, Peter J.,Hughes, Michael L.,Searle, Patricia M.,Wood, Albert S.
, p. 244 - 253 (2013/09/06)
The discovery and scale-up of two routes to sampatrilat are described. The first Chemical R and D route used a side product from another development project to accelerate drug supply and expedite the early development programme. The second, more efficient Chemical R and D route had the potential for commercialisation and used an environmentally friendly variant of the Baylis-Hillman reaction, and an asymmetric Michael addition as key steps. Full preparative details for the aminomethacrylate 4, a potentially useful chiral synthon, are given for the first time, along with full experimental details of the asymmetric Michael addition to make the chiral glutarate 5. Finally, a striking polymorph case history is described.
Salts of 3-azabicyclo [3.3.1]nonanes as antiarrhythmic agents, and precursors thereof
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, (2008/06/13)
Salts of 3-azabicyclo[3.3.1]nonanes are used in controlling antiarrhythmic processes and precursors thereof are disclosed.
Salts of 3-azabicyclo[3.3.1]nonanes as antiarrhythmic agents, and precursors thereof
-
, (2008/06/13)
Salts of 3-azabicyclo[3.3.1]nonanes are used in controlling antiarrhythmic processes and precursors thereof are disclosed.
Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza bunge (Danshen)
Chang,Chui,Tan,Yang,Zhong,Lee,Sham,Wong
, p. 1675 - 1692 (2007/10/02)
Twenty one o-quinonoid-type compounds and one coumarin-type compound related to miltirone (1) have been synthesized with the aim to identify the key structural elements involved in miltirone's interaction with the central benzodiazepine receptor. On the basis of their inhibition of [3H]flunitrazepam binding to bovine cerebral cortex membranes, it is apparent that ring A of miltirone is essential for affinity. Although increasing the size of ring A from six-membered to seven- and eight-membered is well-tolerated, the introduction of polar hydroxyl groups greatly reduces binding affinity. The presence of 1,1-dimethyl groups on ring A is, however, not essential. On the other hand, the isopropyl group on ring C appears to be critical for binding as its removal decreases affinity by more than 30-fold. It can, however, be replaced with a methyl group with minimal reduction in affinity. Finally, linking ring A and B with a -CH2CH2- bridge results in analogue 89, which is 6 times more potent than miltirone at the central benzodiazepine receptor (IC50 = 0.05 μM).
Preparation of t-Butyl 2-(Phenylthiomethyl)propenoate, t-Butyl 3-(Phenylthio)-2-(phenylthiomethyl)propenoate and Related Compounds
Haynes, Richard K.,Katsifis, Andrew,Vonwiller, Simone C.
, p. 1571 - 1578 (2007/10/02)
The preparation of t-butyl 2-(phenylthiomethyl)propenoate, t-butyl and methyl 3-(phenylthio)-2-(phenylthiomethyl)propenoate, the corresponding carboxylic acids, and 3-(phenylthio)-2-(phenylsulfinylmethyl)propenoate from 3-bromo-2-(bromomethyl)propionic acid is described.
