title: Chemoselective Preparation of Clickable Aryl Sulfonyl Fluoride Monomers: A Toolbox of Highly Functionalized Intermediates for Chemical Biology Probe Synthesis.
abstract: Sulfonyl fluoride (SF)-based activity probes have become important tools in chemical biology. Herein, exploiting the relative chemical stability of SF to carry out a number of unprecedented SF-sparing functional group manipulations, we report the chemoselective synthesis of a toolbox of highly functionalized aryl SF monomers that we used to quickly prepare SF chemical biology probes. In addition to SF, the monomers bear an embedded click handle (a terminal alkyne that can perform copper(I)-mediated azide-alkyne cycloaddition). The monomers can be used either as fragments to prepare clickable SF analogues of drugs (biologically active compounds) bearing an aryl ring or, alternatively, attached to drugs as minimalist clickable aryl SF substituents.
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors: Olugbeminiyi
authors: O
authors: Fadeyi
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors: Mihir D
authors: MD
authors: Parikh
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors: Ming Z
authors: MZ
authors: Chen
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors: Robert E
authors: RE
authors: Kyne
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors: Alexandria P
authors: AP
authors: Taylor
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Inish
authors: I
authors: O'Doherty
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Stephen E
authors: SE
authors: Kaiser
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Sabrina
authors: S
authors: Barbas
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Sherry
authors: S
authors: Niessen
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Manli
authors: M
authors: Shi
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: Scott L
authors: SL
authors: Weinrich
authors: Oncology RU Medicinal Chemistry, Pfizer Inc., 10770 Science Center Drive, San Diego, CA, 92121, USA.
authors: John C
authors: JC
authors: Kath
authors: Medicine Design, Pfizer Inc., 610 Main Street, Cambridge, MA, 02139, USA.
authors: Lyn H
authors: LH
authors: Jones
authors: Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA. ralph.p.robinson@pfizer.com.
authors: Ralph P
authors: 0000-0002-4066-5299
authors: RP
authors: Robinson
mesh_terms: D057930:Click Chemistry; D008958:Models, Molecular; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013441:Sulfinic Acids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D015335:Molecular Probes; D013441:Sulfinic Acids; C048899:sulfuryl fluoride
keywords: chemical biology; click chemistry; medicinal chemistry; proteomics; sulfonyl fluoride