5. Dpm – an Acid-Labile Group Orthogonal to Mmt

Dpm (diphenylmethyl) was developed by Alberico et al. as an acid-cleavable protecting group that is fully orthogonal to Mmt. For the targeted synthesis of two disulfide bridges, so far the most commonly used protecting group combination used to be Trt (trityl) and Mmt (4-methoxytrityl). As Mmt can be removed with 1% TFA and Trt requires a higher concentration for removal (ca. 7-10%), in principal a certain degree of orthoganality is given. However, in large scale syntheses it is necessary to utilize 5% TFA for Mmt removal to achieve complete cleavage. At this concentration, it can be observed that significant parts of Trt are already cleaved as well. Therefore, no true orthogonality is provided by this protecting group pair.

Orthogonality between Mmt and Trt (left), and Mmt and Dpm (right).

The situation is different when using Mmt in combination with Dpm. The Dpm group requires at least 60% TFA for cleavage, so it remains fully stable under Mmt cleavage conditions. Thus, using Mmt and Dpm, full orthogonality can be achieved.

Cleavage conditions: Mmt: cleavage with 5% TFA Dpm: min. 60%, usually 90% TFA in DCM to achieve complete cleavage

FAA3190 Fmoc-L-Cys(Dpm)-OH

N-alpha-(9-Fluorenylmethyloxycarbonyl)-S-diphenylmethyl-L-cystei- ne FORMULA: C 31 H 27 NO 4 S MOLECULAR WEIGHT: 509,62 g/mol Article No. Quantity Price

O H N

S O O

(R) OH

FAA3190.0025 25 g € 170,00

FAA3190.0100 100 g € 450,00

References: f Acid-labile Cys-protecting groups for the Fmoc/tBu strategy: filling the gap; M. Gongora-Benitez, L. Mendive-Tapia, I. Ramos-Tomillero, A. C. Breman, J. Tulla-Puche and F. Albericio; Org Lett 2012; 14: 5472-5. doi:10.1021/ol302550p