Synthesis and Protection of Aryl Sulfates Using the 2,2,2-Trichloroethyl Moiety

Abstract

[reaction: see text] The 2,2,2-trichloroethyl (TCE) group was utilized as the first protecting group for aryl sulfates. Aryl sulfates, protected with the TCE group, were prepared in high yield by reacting phenols with chlorosulfuric acid TCE ester. Deprotection was accomplished using Pd/C-ammonium formate or with Zn-ammonium formate to give aryl sulfate monoesters in high yield. This approach to aryl sulfate synthesis was successfully applied to the construction of estrone sulfate derivatives, which could not be prepared by previous methodologies.

Multiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide‐Generating Suicide Inhibitors

“…Several years ago we suggested that estrone sulfate (E1S) derivatives 1-4 could potentially act as suicide inhibitors of STS. [2] Hydrolysis of the SÀO bonds in 1-4 by STS would produce quinone methides in the active site that could react with residues required for catalysis, thus inactivating STS (as illustrated for compound 1 in Scheme 2). Herein we show that several of these compounds are suicide inhibitors of STS.…”

“…[2] Compounds 3 and 4 were prepared by using a similar approach (Scheme 3). [3] A trichloroethyl-protected sulfate group was introduced onto 4-formyl estrone (4-FE1) [4] by using trichloroethylsulfuryl chloride [2] to give compound 5.…”

Introduction of 2,2,2‐Trichloroethyl‐Protected Sulfates into Monosaccharides with a Sulfuryl Imidazolium Salt and Application to the Synthesis of Sulfated Carbohydrates

“…[5] Recently, we described the use of the 2,2,2-trichloroethyl (TCE) group as the first protecting group developed for aryl sulfates. [6] The TCE-protected sulfate esters were prepared in a single step by the reaction of phenols with 2,2,2-trichloroethyl chlorosulfate (TCECS) in the presence of triethylamine. The resulting protected sulfates were stable to a variety of conditions, but were readily deprotected in excellent yields under neutral conditions with Pd/C-ammonium formate or zinc-ammonium formate.…”

Divergent Synthesis of Lamellarin α 13-Sulfate, 20-Sulfate, and 13,20-Disulfate

“…5,6 For the structure-activity relationship studies concerning integrase inhibition and anti-HIV activity, we needed to prepare lamellarin 13-sulfate (2) and 13,20-disulfate (4) also. It was revealed, however, the synthesis of 2 from 5 was difficult because debenzylation at 20-OBn occurred simultaneously during deprotection at 13-Oi-Pr under the standard BCl 3 conditions.…”

“…Thus, we designed a new lamellarin derivative (6) in which 13-OH was protected by a more labile methoxymethyl (MOM) group. In this communication, we report a divergent synthesis of lamellarin sulfate derivatives (1), (2), and (4) from the common intermediate (6) which in turn can be obtained from 3,4-dihydroxypyrrole bistriflate (7) and arylboronic acids (8), (9) using the previously established procedure developed in our laboratories (Scheme 1). …”