Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.
Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006 Logroño, La Rioja, Spain.
Org Lett. 2022 Sep 23;24(37):6810-6815. doi: 10.1021/acs.orglett.2c02715. Epub 2022 Sep 9.
Efficient methodologies for synthesizing enantiopure α-deuterated derivatives of serine, cysteine, selenocysteine, and 2,3-diaminopropanoic acid have been developed. H/D exchange was achieved by deprotonation of a chiral bicyclic serine equivalent followed by selective deuteration. Additionally, diastereoselective additions of thiols, selenols, and amines to a chiral bicyclic dehydroalanine in deuterated alcohols allowed site-selective deuteration at the Cα atom of cysteine, selenocysteine, and 2,3-diaminopropanoic acid derivatives. A deuterated analogue of carbocysteine, a drug for the treatment of bronchiectasis, was synthesized.
已开发出高效的方法来合成丝氨酸、半胱氨酸、硒代半胱氨酸和 2,3-二氨基丙酸的对映纯α-氘代衍生物。通过手性双环丝氨酸等价物的去质子化，然后进行选择性氘代反应实现 H/D 交换。此外，在手性双环脱氢丙氨酸的氘代醇中，硫醇、硒醇和胺的立体选择性加成允许在半胱氨酸、硒代半胱氨酸和 2,3-二氨基丙酸衍生物的 Cα 原子上进行位点选择性氘代。一种用于治疗支气管扩张症的药物卡络磺钠的氘代类似物被合成。
