Bolitho Megan E, Corcoran Brendan J, Showell-Rouse Emily I, Wang Keeshia Q
University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
Carbohydr Res. 2014 Jul 23;394:32-8. doi: 10.1016/j.carres.2014.05.009. Epub 2014 May 22.
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.
通过S - 核糖基高半胱氨酸酶（LuxS）裂解S - D - 核糖基 - L - 高半胱氨酸（SRH）的硫醚键，是细菌产生群体感应自诱导物AI - 2生物合成的最后一步。本文介绍了一种经过改进的SRH化学合成方法，其规模和纯度便于进行LuxS的体外研究。双（三甲基硅基）氨基钾（KHMDS）被确定为一种明智的碱，用于从易于获得的前体形成目标化合物的硫醚：一种由L - 高胱氨酸衍生的硫醇亲核试剂和一种磺酸酯活化的D - 核糖基亲电试剂。仅使用对酸不稳定的保护基团可实现最终产物的简便脱保护，通过五步合成以26%的总收率得到SRH的三氟乙酸盐。化学合成的材料以高纯度分离，并通过体外测定证明可作为LuxS的底物。
