[993-12-4] · C2H6ClPS · Dimethylphosphinothioyl Chloride · (MW 128.57)
Alternate Name: Mpt-Cl.
Physical Data: mp 24-25 °C; bp 107-107.5 °C/16 mmHg; bp 69-70 °C/11 mmHg;5 nD20 1.546.
Form Supplied in: liquid; commercially available.
Handling, Storage, and Precautions: stable for several months in a refrigerator.1 Should be handled in the fume hood.
The dimethylphosphinothioyl (Mpt) group has been used to protect N-amino acids. It is more readily removed than t-butoxycarbonyl group, making it a convenient reagent for solid phase synthesis (eq 1).1
This method has been effectively demonstrated in the synthesis of the opioid agonist L-Leu-enkaphalin (L-Tyr-Gly-Gly-L-Phe-L-Leu).
Mpt-Cl also reacts rapidly with N-protected amino acids in the presence of Triethylamine to afford Mpt mixed anhydrides (Mpt-MA). These mixed anhydrides can be isolated by silica-gel column chromatography and stored without decomposition in a freezer. Cbz-Ser-Mpt-MA has been isolated in 17% yield, without protection of the side-chain hydroxy group (eq 2).8,9 As a consequence, these active Mpt-MAs have been used for peptide synthesis in methanol or ethanol rather than the usual dipolar aprotic solvents (HMPA, DMF, or DMSO). Synthesis of a heptapeptide (1) has been completed by this method.2
Hydroxy groups of carbohydrates can be protected using Mpt-Cl in the presence of 1,8-Diazabicyclo[5.4.0]undec-7-ene and catalytic amounts of 4-Dimethylaminopyridine. The Mpt group is stable to acidic hydrolysis conditions that cleave trityl and isopropylidene (acetonide) groups, DBU/MeOH, Bu4NF, Bu3SnH, Grignard reagents, and cat. NaOMe/MeOH. The Mpt group does not migrate as do acyl groups (carboxylate esters) under acidic and basic conditions.4
Mpt-Cl has been used in the stereoselective synthesis of B-glucopyranomides.3
Harjinder S. Bansal
Zeneca Agrochemicals, Bracknell, UK