A Biomimetic Synthesis of Thiazolines Using Hexaphenyloxodiphosphonium Trifluoromethanesulfonate

Abstract

Most chemical syntheses of thiazolines use serine residues, whereas nature employs cysteine residues. In a biomimetic approach, [(Ph3P+)2O](OTf−)2 was used to promote triphenylmethyl (Tr) deprotection and dehydrocyclization of simple cysteine N‐amides to give thiazolines in excellent chemical and optical yields (see scheme). This mild method was extended to the synthesis of, for example, thiazolines from cysteine‐containing dipeptides in high yield and without significant loss of chirality at the C2‐exomethine carbon atom. TF=trifluoromethanesulfonyl, Cbz=benzyloxycarbonyl

Research Progress of Apratoxin A：A Marine Cyclicdepsipeptide with Significant Anti-cancer Activity

“…[7] . 不久之后, Kelly 组 亦采用了 Kelly 新发展的方法 [15] . 以分为两类: 一类是通过天然药物化学的途径, 通过比 较 apratoxin A 与其它结构相近的天然产物活性差别得 出一定的构效关系; 另一类是通过有目的的理性设计, 从合成药物化学的角度研究其构效关系.…”

Synthesis of Macrocyclic Lactams and Lactones Containing Sulfur and Nitrogen

“…Формирование тиазол-тиазолинового фрагмента в аминокислоте 94 проведено последовательностью ре-акций, включающих замену оксо-группы доступного [59] 2-азидоацетамида 96 на тио-функцию при обработке реагентом Лоусона, взаимодействие с этилбромпирува-том, приводящее к образованию тиазольного фрагмента соединения 97, взаимодействие соответствующей ему кислоты с защищенным α-метилцистеином и циклиза-цию, согласно [60] , полученного функционализированно-го амида 98 с образованием тиазолина 99 (Схема 27).…”

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

“…The structure was conclusively determined by X-ray diffraction crystallography which revealed the anticipated O-bridged bis-phosphonium salt. 7 Furthermore, in order to ensure that the solid-state structure was consistent with the reactive intermediates in solution, the 31 P NMR spectrum of the crystallized bis-phosphonium salt was compared to those of reagents prepared with various stoichiometric amounts of Ph 3 …”

“…7 In this context, dehydrocyclization required activation of the amide group with concurrent deprotection of the trityl protecting group to unveil the nucleophilic thiol group. The thiazoline ring would then form by nucleophilic attack of the free cysteine thiol on the phosphonium-activated amide carbonyl group of the former residue, followed by dehydration via the elimination of Ph 3 PO.…”

“…26 Consequently, the design of enantiospecific routes to imidazolines and their derivatives constitutes an important step toward the construction and biological evaluation of macrolactam natural product analogues containing these heterocycles. Building on their early success of the biomimetic synthesis of thiazolines using 1, 7 Kelly and You showcased the versatility of the 'POP' reagent in the highly efficient enantiospecific synthesis of imidazolines. 27 Therefore, starting from N-acylated β-tosylamino-α-acylamino esters, the proposed formation of imidazolines by the diphosphonium salt 1 was examined under the conditions shown in Table 12.…”