181023-09-6Relevant articles and documents
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 (2004)
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.
Enantioselective enzymatic aminolysis of a racemic 2-isoxazolylacetate alkyl ester
Sigmund, Amy E.,McNulty, Kenneth C.,Nguyen, Dzuy,Silverman, Charlotte E.,Ma, Philip,Pesti, Jaan A.,DiCosimo, Robert
, p. 608 - 612 (2002)
Pseudomonas cepacia lipase or Candida antartica lipase B catalyzes the enantioselective aminolysis of a racemic 2-isoxazolylacetate alkyl ester, isobutyl 2-[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate, by 3-amino-N-(butoxycarbonyl)-L-alanine methyl ester, mono(4-methylbenzenesulfonate) to produce the corresponding amide, (R)-methyl-3-[[[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetyl]amino]-N- (butoxycarbonyl)-L-alanine, which is an intermediate in the preparation of an isoxazoline-based platelet glycoprotein IIb/IIIa antagonist.
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.
