Dimethyl Sulfide → HDTrp-Leu-MetNH2 trifluoroacetate
Reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@@H:2]([C:13]([NH:15][C@H:16]([C:21]([NH:23][C@H:24]([C:29]([NH2:31])=[O:30])[CH2:25][CH2:26][S:27][CH3:28])=[O:22])[CH2:17][CH:18]([CH3:20])[CH3:19])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42].CSC.C(S)(S)C>>[NH2:1][C@@H:2]([C:13]([NH:15][C@H:16]([C:21]([NH:23][C@H:24]([C:29]([NH2:31])=[O:30])[CH2:25][CH2:26][S:27][CH3:28])=[O:22])[CH2:17][CH:18]([CH3:20])[CH3:19])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[F:39][C:40]([C:41]([OH:43])=[O:42])([F:45])[F:44]Participants
Procedure
Condensation of BocDTrpOPFP (4.70 g.) and HLeu-MetNH2 hydrochloride salt (Example 1, 2.98 g.) by the activated ester method using ethyldiisopropylamine gave BocDTrp-Leu-MetNH2 in 71% yield. De-t-butoxycarbonylation of BocDTrp-Leu-MetNH2 using trifluoroacetic acid, methyl sulfide, and ethanedithiol gave HDTrp-Leu-MetNH2 trifluoroacetate salt in 100% yield. Condensation of BocD,LBpaOH (2.95 g.) and HDTrp-Leu-MetNH2 trifluoroacetate salt (3.79 g.) by the mixed anhydride method using diphenylphosphinyl chloride and separation of the diastereoisomers by column chromatography on silica gel using chloroform-methanol (91:9) as eluant gave BocLBpa-DTrp-Leu-MetNH2 and BocDBpa-DTrp-Leu-MetNH2 each in 19% yield. De-t-butoxycarbonylation of BocLBpa-DTrp-Leu-MetNH2 (0.875 g.) and BocLBpa-DTrp-Leu-MetNH2 (0.875 g.) using trifluroracetic acid in methyl ethyl sulfide and ethanedithiol gave HLBpa-DTrp-Leu-MetNH2 and HDBpa-DTrp-Leu-MetNH2, both as the trifluoroacetate salts and both in 100% yield.
Sources & evidence
- ORD record
- ord-e4d098d2ddbd48258d4129ea93e95bf0
- Source dataset
- uspto-grants-1984_09
- Patent number
- US04472305
Reaction notes
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