181023-08-5Relevant articles and documents
Enantio- And Chemoselective Intramolecular Iridium-Catalyzed O-Allylation of Oximes
Sandmeier, Tobias,Carreira, Erick M.
, p. 2643 - 2647 (2021)
A method for the enantio- and chemoselective iridium-catalyzed O-allylation of oximes is described. Kinetic resolution in an intramolecular setting provides enantioenriched oxime ethers and aliphatic allylic alcohols. The synthetic potential of the products generated with this method is showcased by their elaboration into a series of heterocyclic compounds and the formal synthesis of glycoprotein GP IIb-IIIa receptor antagonist (-)-roxifiban. Preliminary mechanistic experiments and computational data shed light on the remarkable chemoselectivity of the reaction.
Novel chiral auxiliary for attempted resolution of key roxifiban intermediate: A simple diastereoselective coupling approach for the synthesis of roxifiban
Gangopadhyay, Ashok K.,Gole, Gopal V.,Jadhav, Ravindra D.,Lal, Bansi
, p. 4157 - 4171 (2008/03/13)
This article describes a simple method for the synthesis of roxifiban, a potent glycoprotein GP IIb-IIIa receptor antagonist, by a diastereoselective coupling approach to give >99.9% optical purity. We have also described an attempt to resolve the key syn
Efficient Preparation of a Key Intermediate in the Synthesis of Roxifiban by Enzymatic Dynamic Kinetic Resolution on Large Scale
Pesti, Jaan A.,Yin, Jinguao,Zhang, Lin-Hua,Anzalone, Luigi,Waltermire, Robert E.,Ma, Philip,Gorko, Edward,Confalone, Pat N.,Fortunak, Joseph,Silverman, Charlotte,Blackwell, John,Chung,Hrytsak, Michael D.,Cooke, Mary,Powell, Lakisha,Ray, Charles
, p. 22 - 27 (2013/09/04)
Additional information is presented for the transformation of a kinetic resolution into a dynamic kinetic resolution of the isobutyl ester 5b to form the acid 2 in high yield and ee via the intermediacy of a thioester 6c, (Pesti, J. A.; Yin, J.; Zhang, L.-H; Anzalone, L. J. Am. Chem. Soc. 2001, 123, 11075-11076.). The development of optimized reaction conditions for the preparation of 6c, its dynamic kinetic resolution to 2, and the scale-up of both reactions into a pilot plant are described.
The enantiospecific synthesis of an isoxazoline. A RGD mimic platelet GPIIb/IIIa antagonist
Zhang, Lin-Hua,Chung,Costello,Valvis,Ma,Kauffman,Ward
, p. 2466 - 2470 (2007/10/03)
A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and > 99.6% optical purity, starting from L-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of N(α)-n-Boc-L-asparagine with iodosobenzene diacetate provides optically pure N(α)-n-Boc-L-α,β-diaminopropionic acid (8) in 75% yield. A process of lipase resolution-base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.
Discovery of potent isoxazoline glycoprotein IIb/IIIa receptor antagonists
Wityak, John,Sielecki, Thais M.,Pinto, Donald J.,Emmett, George,Sze, Jean Y.,Liu, Jie,Tobin, A. Ewa,Wang, Shuaige,Jiang, Biao,Ma, Philip,Mousa, Shaker A.,Wexler, Ruth R.,Olson, Richard E.
, p. 50 - 60 (2007/10/03)
Using the isoxazoline as a common structural feature, three series of glycoprotein IIb/IIIa receptor antagonists were evaluated, culminating in the discovery of XR299 (30). In an in vitro assay of platelet inhibition, XR299 had an IC50 of 0.24 μM and was a potent antiplatelet agent when dosed intravenously in a canine model. It was shown through X-ray studies of the cinchonidine salt 49 that the receptor required the 5(R)-stereochemistry for high potency. The ethyl ester prodrug of XR299, XR300 (29), was orally active in the dog.
Discovery of an orally active series of isoxazoline glycoprotein IIb/IIIa antagonists
Xue, Chu-Biao,Wityak, John,Sielecki, Thais M.,Pinto, Donald J.,Batt, Douglas G.,Cain, Gary A.,Sworin, Michael,Rockwell, Arlene L.,Roderick, John J.,Wang, Shuaige,Orwat, Michael J.,Frietze, William E.,Bostrom, Lori L.,Liu, Jie,Higley, C. Anne,Rankin, F. Wayne,Tobin, A. Ewa,Emmett, George,Lalka, George K.,Sze, Jean Y.,Di Meo, Susan V.,Mousa, Shaker A.,Thoolen, Martin J.,Racanelli, Adrienne L.,Hausner, Elizabeth A.,Reilly, Thomas M.,DeGrado, William F.,Wexler, Ruth R.,Olson, Richard E.
, p. 2064 - 2084 (2007/10/03)
Using isoxazoline XR299 (la) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions α and β to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u1,2 exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of the benzamidin-4-yl moiety with alternative basic groups, elimination of the isoxazoline stereocenter, and reversal of the orientation of the isoxazoline ring resulted in lowered potency and/or duration of action.
The chiral specific synthesis of DMP 754, a platelet GP IIb/IIIa antagonist
Zhang, Lin-Hua,Anzalone,Ma,Kauffman,Storace,Ward
, p. 4455 - 4458 (2007/10/03)
An effective and chiral specific synthesis of DMP 754 (1), a non- peptide platelet GP IIb/IIIa antagonist, is reported.
