170277-77-7Relevant academic research and scientific papers
Hetero Diels - Alder-biocatalysis approach for the synthesis of (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate, a key intermediate for the synthesis of the PKC inhibitor LY333531
Caille, Jean-Claude,Govindan,Junga, Heiko,Lalonde, Jim,Yao, Yiming
, p. 471 - 476 (2002)
A cost-effective and easily scaled-up process has been developed for the synthesis of (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate, a key intermediate used in the synthesis of a protein kinase C inhibitor drug through a combination of hetero Diels - Alder and biocatalytic reactions. The Diels - Alder reaction between ethyl glyoxylate and bntadiene was used to make racemic 2-ethoxy-carbonyl-3,6-dihydro-2H-pyran. Treatment of the racemic ester with Bacillus lentus protease resulted in the selective hydrolysis of the R-enantiomer and yielded S-2-ethoxycarbonyl-3,6-dihydro-2H-pyran in excellent optical purity, which was reduced to S-3,6-dihdro-2H-pyran-2-yl methanol. Tritylation of this alcohol, followed by reductive ozonolysis and mesylation afforded the product in 10-15% overall yield and with >99% ee and chemical purity. Details of the process development work done on each step are given.
Highly diastereoselective hetero-Diels-Alder reaction of buta-1,3-diene with N-glyoxyloyl-(2R)-bornane-10,2-sultam: An efficient synthesis of homochiral (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate
Kosior, Malgorzata,Malinowska, Malgorzata,Jozwik, Julita,Caille, Jean-Claude,Jurczak, Janusz
, p. 239 - 244 (2003)
The influence of Lewis acid on the diastereoselectivity of [4+2] cycloaddition of buta-1,3-diene to N-glyoxyloyl-(2R)-bornane-10,2-sultam was investigated and high levels of asymmetric induction were achieved. (S)-3-[2-{(Methylsulfonyl)oxy}ethoxy]-4-(trip
Process for producing butanetriol derivative
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, (2008/06/13)
A process for preparing a butanetriol derivative of the formula (1) useful as intermediates of medicines wherein R1is the same defined below, which comprises reacting a compound of the formula (3) wherein R1and R2are the different protecting groups, and an ethylene glycol derivative in a basic condition to prepare a compound of the formula (4) or (4a) wherein R1and R2are the same defined above, and then subjecting the compound (4) or (4a) to selective deprotection reaction.
Macrocyclic bisindolylmaleimides: Synthesis by inter- and intramolecular alkylation
Faul, Margaret M.,Winneroski, Leonard L.,Krumrich, Christine A.,Sullivan, Kevin A.,Gillig, James R.,Neel, David A.,Rito, Christopher J.,Jirousek, Michael R.
, p. 1961 - 1973 (2007/10/03)
Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC β1 and β2 and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active the compound, proceeds in 11 steps and 26% overall yield (> 98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 17 steps and affording 1-4 in lower overall yields of 6.0-8.5%.
Synthesis of bisindolylmaleimides
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, (2008/06/13)
The present invention provides a novel synthesis of the compounds of Formula (I): STR1 The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereosel
