Dimethylphosphinothioyl Chloride

[993-12-4]  · C2H6ClPS  · Dimethylphosphinothioyl Chloride  · (MW 128.57)

(reagent for protection in peptide1,2 and carbohydrate3,4 synthesis)

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.

Preparative Method: chlorination of tetramethyldiphosphine disulfide7 with Sulfuryl Chloride.1,6

Handling, Storage, and Precautions: stable for several months in a refrigerator.1 Should be handled in the fume hood.

Peptide Synthesis.

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

Carbohydrate Protection/Synthesis.

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

1. Veki, M.; Inazu, T.; Ikeda, S. BCJ 1979, 52, 2424.
2. Veki, M.; Santo, T.; Sasaya, Jun.; Ikeda, S.; Oyamada, H. BCJ 1988, 61, 3653.
3. Yamanoi, T.; Inazu, T. Noguchi Kenkyusho Jiho 1988, 31, 49 (CA 1989, 111, 7684v).
4. Inazu, T.; Yamanoi, T. Noguchi Kenkyusho Jiho 1988, 31, 43 (CA 1989, 111, 7685w).
5. Dictionary of Organophosphorus Compounds; Chapman & Hall: New York, 1988; p 327.
6. Maier, L. CB 1961, 94, 3051.
7. Parshall, G. W. OSC 1973, 4, 1016.
8. Veki, M.; Okazaki, K.; Sano, Y.; Ikeda, S. Pept., Proc. Eur. Peptide Symp. 1984, 1814.
9. Veki, M.; Inazu, T. CL 1982, 45.

Harjinder S. Bansal

Zeneca Agrochemicals, Bracknell, UK

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