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.
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
-
, (2008/06/13)
Salts of 3-azabicyclo[3.3.1]nonanes are used in controlling antiarrhythmic processes and precursors thereof are disclosed.
