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Chemical Structure| 266359-42-6 Chemical Structure| 266359-42-6

Structure of 266359-42-6

Chemical Structure| 266359-42-6

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Product Details of [ 266359-42-6 ]

CAS No. :266359-42-6
Formula : C24H27NO5
M.W : 409.47
SMILES Code : O=C([C@H]1N(C(OCC2C3=C(C4=C2C=CC=C4)C=CC=C3)=O)CC[C@@H]1OC(C)(C)C)O
MDL No. :MFCD22375522

Safety of [ 266359-42-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 266359-42-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 266359-42-6 ]

[ 266359-42-6 ] Synthesis Path-Downstream   1~1

  • 1
  • N-(9-fluorenylmethyloxycarbonyl)-3-(cis-4-hydroxycyclohexyl)-D-alanine [ No CAS ]
  • N-(2-(tert-butoxy)-2-oxoethyl)-N-(tert-butoxycarbonyl)-L-phenylalanine [ No CAS ]
  • [ 143824-78-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 147290-11-7 ]
  • [ 266359-42-6 ]
  • (3R,6S,9S,15S)-15-((S)-2-((2-(tert-butoxy)-2-oxoethyl)(tert-butoxycarbonyl)amino)-3-phenylpropanamido)-1-((2S,4R)-4-(tert-butoxy)pyrrolidin-2-yl)-6-((1-(tert-butoxycarbonyl)-1H-indol-3-yl)methyl)-3-((4-hydroxycyclohexyl)methyl)-1,4,7,10-tetraoxo-9-(3-(3-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)guanidino)propyl)-2,5,8,11-tetraazahexadecan-16-oic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% In an SPPS vessel equipped with an overhead mechanical stirrer, CTC resin (1.0-1.7meq/g,1 .0 equiv.) was mixed with a solution of a selected Fmoc-protected amino acid(1.1 equiv.) and DIPEA (6 equiv.) in a mixed solvent of DMF/DCM (1:10 v/v76.6 ml/mmol of CTC resin). The mixture was gently stirred at r.t. for 5 h. Anhydrousmethanol (16 equiv.) was added to cap any unreacted CTC resin. After being stirred atr.t. for another 30 mm, the solution was removed from the resin by vacuum filtration.The resin-bound product was washed with DMF (3x200 ml), DCM (3x200 ml), MeOH(3x200 ml), and DMF (3x200 ml). For Fmoc removal the resin was then treated with20% v/v piperidine in DMF (300 ml) at r.t. with gentle stirring for 30 mm. The resin wasthen filtered under vacuum, washed with DMF (3x200 ml), DCM (3x200 ml), MeOH (3x100 ml) and dried completely under vacuum to afford the CTC resin-bound amino acid which was used in solid phase synthesis directly without any further purification. The resin loading rate was estimated based on the weight increase compared to the non-loaded resin.; The resin-bound pentapeptide or hexapeptide was treated with a solution of HFIPA inDCM (20% v/v7 12 ml/mmol of substrate) in an SPPS vessel with gentle stirring at r.t. for30 mm. The mixture was filtered and filtrate collected. The resin was treated withanother identical volume of 20% v/v HFIPA in DCM at r.t. upon gentle stirring for another 30 mm, and filtered again. The filtrates were combined and evaporated under vacuum to dryness to afford the linear pentapeptide or hexapeptide.; (1.0 equiv.) was loaded onto CTC resin using Method C. In a SPPS vessel equipped with overhead mechanical stirrer, the resin15 bound N6-allyloxycarbonyl-L-ornithine was mixed with a N-protected amino acid(1.3 equiv), HBTU (1.3 equiv.) and DMF (6-6.6 ml/mmol of loaded resin). The mixture was gently stirred at r.t. for about 2 h or until LC-MS indicated the completion of the reaction using Method A. The resin was filtered, washed with DMF (3x200 ml), DCM (3x200 ml) and MeOH (3x100 ml), then dried under vacuum.; Loading.Following Method C, (33.6 g, 76 mmol, 1.5equiv.), CTC resin (1.7 meq, 30.0 g, 51.1 mmol, 1.0 equiv.), DIPEA (72 ml, 406 mmol, 8equiv.) and a mixed solvent of DMF and DCM (1:10 v/v7 330 ml) were used. Themixture was gently stirred at r.t. for 5 h and capped by addition of MeOH (33 ml). Loading rate was estimated to be 81% or 41.3 mmol, based on weight increase of the resin. The resin was then treated with piperidine in DMF (20% v/v) to remove the Fmoc group to afford the CTC resin-bound N6-allyloxycarbonyl-L-ornithine.Side chain amino acid installation.CTC resin-bound N6-allyloxycarbonyl-L-ornithine (46.6 g, 41.3 mmol), N-(2-(tert-butoxy)-2-oxoethyl)-N-(tert-butoxycarbonyl)-L-phenylalanine (20.4 g, 53.7 mmol, 1.30 equiv.),HBTU (21.0 g, 53.7 mmol, 1.30 equiv.), DIPEA (22.6 ml, 128 mmol, 3.1 equiv.) andDMF (250 ml) were gently stirred at r.t. for 120 mm when LC-MS (Method A) indicatedcompletion of the reaction. LC-MS (Method A, 3 mm run): tR 1.92 mm, ESI- [M-H] calculated for C29H41N309 576.6; found 576.5.Alloxycarbonyl removal.The resin-bound dipeptide (S)-5-(((allyloxy)carbonyl)am ino)-2-((S)-2-((2-(tert-butoxy)-2- oxoethyl)(tert-butoxycarbonyl)am ino)-3-phenylpropanam ido)pentanoic acid (47.7 g, 34.2 mmol, 1.0 equiv.) was suspended in DCM (285 ml). The mixture was stirred with phenylsilane (70 ml, 547 mmol, 16 equiv.) and tetrakis(triphenylphosphine)palladium (4.74 g, 4.10 mmol, 0.12 equiv.) at r.t. for 1 h when LC-MS (Method A) indicatedcompletion of the reaction. The resin was filtered out, washed, dried to afford resin- bound (S)-5-am ino-2-((S)-2-((2-(tert-butoxy)-2-oxoethyl)(tert-butoxycarbonyl)am ino)-3- phenylpropanamido)pentanoic acid. LC-MS (Method A, 3 mm run): tR 1.22 mm, ESI[M-H] calculated for C25H37N307 491.6; found 492.4.Further coupling of amino acids and cleavage of linear peptide from the resin.Preparation of (3R,6S,9S, 1 5S)-1 5-((S)-2-((2-(tert-butoxy)-2-oxoethyl)(tert-butoxycarbonyl)am ino)-3-phenylpropanam ido)-1 -((2S,4R)-4-(tert-butoxy)pyrrolidin-2-yl)- 6-((1 -(tert-butoxycarbonyl)-1 H-indol-3-yl)methyl)-3-(((1 s,4S)-4-hydroxycyclohexyl)methyl)-1 4,7,1 0-tetraoxo-9-(3-(3-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yI)sulfonyl)guanidino)propyl)-2,5,8,1 1 -tetraazahexadecan-1 6-oic acid (the linear hexapeptide).Resin-bound (S)-5-am ino-2-((S)-2-((2-(tert-butoxy)-2-oxoethyl)(tert-butoxycarbonyl)amino)-3-phenylpropanamido)pentanoic acid (28.5 mmol, 1.0 equiv.) was subject to the solid phase coupling and Fmoc removal procedures described in Method G sequentially with pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginine (33.3 g, 42 mmol, 1.5 equiv.), -(tert-butoxycarbonyl)-L-tryptophan(30.0 g, 57 mmol, 2.0 equiv.), N-(9-Fluorenylmethyloxycarbonyl)-3-(cis-4- hydroxycyclohexyl)-D-alanine (15.2 g, 37 mmol, 1.3 equiv.), and trans-3-t-butoxy-N-(9- fluorenylmethyloxycarbonyl)-L-proline (15.2 g, 37 mmol, 1.3 equiv.) to afford the...
 

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