Bis[2‐(methylsulfonyl)ethyl] phosphochloridate, a new phosphorylating agent

Abstract

This communication describes the application of the 2‐(methylsulfonyl)ethyl group (Mse) as a base‐labile protecting group for the two hydroxyl functions in phosphoric acid monoesters. Due to its perfect stability towards acids, the Mse group can function as a stable protecting group in a phosphochloridate, providing a suitable phosphorylating agent. Some model phosphorylations are presented, and the reaction is applied to the synthesis of bis[2‐(methylsulfonyl)ethyl] tyrosine phosphate. Removal of the Mse functions is achieved effectively and extremely rapidly in alkaline media. The estimation of the minimum conditions necessary for the removal of one or both Mse functions from bis[2‐(methylsulfonyl)ethyl] p‐nitrophenyl phosphate and from a tyrosine derivative is described.

A Convenient Method to Prepare Labile FMN Derivatives

“…We now present a new method yielding selectively phosphorylated products in pure form, involving only a few synthetic steps. Beld et al [ 5 ] have synthesized a new phosphorylating agent, bis[2-(methylsulfonyl)ethyl] phosphochloridate, which is easily synthesized in almost quantitative yield and exhibits a higher specificity with regard to the phosphorylation site of nucleosides than other agents. Compound 1 ( Scheme 1 ), a versatile chemical for the synthesis of many riboflavin derivatives, was phosphorylated with bis[2-(methylsulfonyl)ethyl] phosphochloridate in pyridine abs.…”

Synthesis of Photoaffinity Derivatives of Adenophostin A

“…Phosphitylation of the alcohol functions in 13 with N,N-diisopropylbis [2-(methylsulfonyl)ethyl] (MSE) phosphoramidite, assisted by 1H-tetrazole, [20] and in situ oxidation of the intermediate phosphite triesters with tert-butyl hydroperoxide, afforded trisphosphate 14. Deprotection of 14 was accomplished by removal of the base-labile groups with Tesser's base, [21] followed by hydrogenolysis of the remaining benzyl ethers to give, after purification by HW-40 gel filtration and Dowex Na ϩ ion-exchange chromatography, the homogeneous 5Ј-amino derivative of adenophostin A (15, Na ϩ salt). The observed low yield (27%) of intermediate 14 may be due to the occurrence of an undesired Staudinger reaction [22] of the 5Ј-azide functionality with the phosphoramidite reagent.…”

Oligomerizations of deoxyadenosine bis-phosphates and of their 3′-5′, 3′-3′, and 5′-5′ dimers: Effects of a pyrophosphate-linked, poly(t) analog

“…Thymidine was first phosphorytated at the 5'-position using 1.1 equivalents of bis [2-(methylsulphonyl)-ethyl]phosphorochloridate in pyridine at 0 °C for 3 hr (Beld et al, 1984). Subsequently the T-position was (Wreesman et at., 1985).…”