23518-25-4Relevant articles and documents
Stereocontrolled organocatalytic synthesis of prostaglandin PGF 2α in seven steps
Coulthard, Graeme,Erb, William,Aggarwal, Varinder K.
, p. 278 - 281,4 (2020/07/31)
Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made prostaglandins popular targets for synthetic organic chemists for over 40 years. Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma, have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF 2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups. Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.
BF3-MEDIATED REACTION OF A SULPHONE WITH ALDEHYDES. A METHOD FOR STEREOSPECIFIC CONSTRUCTION OF PROSTAGLANDIN ω-CHAIN
Achmatowicz, B.,Baranowska, E.,Daniewski, A. R.,Pankowski, J.,Wicha, J.
, p. 4989 - 4998 (2007/10/02)
A new method for stereospecific construction of the allylic alcohol moiety of prostaglandins, based on application of optically active α-hydroxy aldehydes, is described.In the presence of BF3*Et2O, lithiated sulphones 1 prepared from Corey aldehyde, and carbonyl compounds 2 give the corresponding adducts 3 in moderate to excellent yields, while in the absence of the Lewis acid either no products or only their traces were formed.The addition products 3, in the form of benzoates, mesylates or free alcohols, were subjected to reductive elimination by means of sodium amalgam to give the alkenes 4.Compounds 4d and 4f were transformed into racemic and natural PGF2α, respectively, in line with the known method.
A NOVEL APPROACH TO PROSTAGLANDINS FROM THE COREY LACTONE INVOLVING BF3-MEDIATED REACTIONS OF A SULPHONE AND ALDEHYDES
Achmatowicz, B.,Baranowska, E.,Daniewski, A. R.,Pankowski, J.,Wicha, J.
, p. 5597 - 5600 (2007/10/02)
Transformation of the diol 1 via epimeric sulphones 7 to PGF2α is described.Alkylation of lithiated sulphones 7 with aldehydes 8a, 8b or 8c in the presence of BF3 efficiently gives corresponding adducts.
