title: Revisiting synthetic preparation of the quorum sensing substrate S-D-ribosyl-L-homocysteine (SRH).
abstract: Cleavage of the thioether bond of S-D-ribosyl-L-homocysteine (SRH) by the enzyme S-ribosylhomocysteinase (LuxS) serves as the final biosynthetic step in the generation of the quorum sensing autoinducer AI-2 by bacteria. Herein, a revised chemical synthesis of SRH is presented at convenient scale and purity for in vitro studies of LuxS. Potassium bis(trimethylsilyl)amide (KHMDS) is identified as a judicious base for the formation of the thioether of the target compound from readily-accessible precursors: a thiol nucleophile derived from l-homocystine and a sulfonate-activated d-ribosyl electrophile. The exclusive use of acid-labile protecting groups allows for facile deprotection to the final product, producing the TFA salt of SRH in five synthetic steps and 26% overall yield. The chemically-synthesized material is isolated at high purity and demonstrated to serve as the LuxS substrate by an in vitro assay.
authors: University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA. Electronic address: mebolitho@usfca.edu.
authors: Megan E
authors: ME
authors: Bolitho
authors: University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
authors: Brendan J
authors: BJ
authors: Corcoran
authors: University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
authors: Emily I
authors: EI
authors: Showell-Rouse
authors: University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
authors: Keeshia Q
authors: KQ
authors: Wang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000737:chemistry / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D053038:Quorum Sensing
chemical_list: D001426:Bacterial Proteins; C487472:S-ribosyl-L-homocysteine; D006710:Homocysteine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria
keywords: Autoinducer-2 (AI-2); Quorum sensing (QS); S-Ribosylhomocysteinase (LuxS); S-d-Ribosyl-l-homocysteine (SRH)