170277-79-9

Upstream product

• 67-56-1 methanol 
• 75-09-2 dichloromethane 
• 170277-78-8 1,1',1''-[[[(2S)-4-methyl-2-(2-propen-1-yloxy)-4-penten-1-yl]-oxy]methylidyne]trisbenzene 
• 76-83-5 trityl chloride 
• 172323-66-9 (S)-(-)-(3,6-Dihydro-2H-pyran-2-yl)methanol 
• 42757-04-0 ethyl 3,6-dihydro-2H-pyran-2-carboxylate 
• 233666-31-4 (S)-4-benzyloxy-2-(2-benzyloxyethoxy)-1-trityloxybutane 
• 203250-06-0 (R)-3-chloro-1-O-trityl-1,2-propanediol 
• 129940-50-7 (S)-tritylglycidol 
• 170277-82-4 (2S)-1-triphenylmethoxy-4-pentene-2-ol 
• 3292-82-8 α-trityloxyacetaldehyde 
• 1235-22-9 allyl trityl ether 
• 364730-56-3 (S)-2-trityloxymethyl-3,6-dihydro-2H-pyran 

Downstream Products

• 170277-74-4 (9S)-6,7,10,11-tetrahydro-19-methyl-9-[(triphenylmethoxy)-methyl]-9H,18H-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h]-[1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione 
• 203250-04-8 (S)-4-(triphenylmethoxy)-2-(2-chloroethoxy)-1-chlorobutane 
• 203250-05-9 (S)-4-(triphenylmethoxy)-2-(2-iodoethoxy)-1-iodobutane 
• 203250-03-7 (S)-4-(triphenylmethoxy)-2-(2-bromoethoxy)-1-bromobutane 
• 170277-77-7 (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate 

Relevant academic research and scientific papers

Synthesis and Characterization of the Selective, Reversible PKCβ Inhibitor (9 S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4- h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531)

The demonstrated role of PKCβ in mediating amphetamine-stimulated dopamine efflux, which regulates amphetamine-induced dopamine transporter trafficking and activity, has promoted the research use of the selective, reversible PKCβ inhibitor (9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione, ruboxistaurin. Despite the interest in development of ruboxistaurin as the mesylate monohydrate (Arxxant) for the treatment of diabetic retinopathy, macular edema, and nephoropathy, several crucial details in physicochemical characterization were erroneous or missing. This report describes the synthesis and full characterization of ruboxistaurin free base (as a monohydrate), including X-ray crystallography to confirm the absolute configuration, and of the mesylate salt, isolated as a hydrate containing 1.5 mol of water per mole.

Process for producing butanetriol derivative

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.

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

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

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

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.

Enantioselective allyltitanations. Synthesis of optically active 1,2- diol units: Useful intermediates for the preparation of biologically active compounds

1,2-Diol units were synthesized with excellent enantiomeric excess by using an enantioselective allyltitanation of α-alkoxy-substituted aldehydes.

Macrocyclic bisindolylmaleimides: Synthesis by inter- and intramolecular alkylation

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

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