Convergent Synthesis of (−)-Mirabazole C Using a Chloroimidazolidium Coupling Reagent, CIP

Abstract

Convergent synthesis of (−)-mirabazole C (1), a tetra thiazoline/thiazole alkaloid isolated from blue-green alga, has been described. The successive thiazoline rings of (−)-mirabazole C were formed by a single-step cyclization mediated by TiCl4 treatment of tripeptide amide 4. Convergent synthesis of the key intermediate 33 derived from three 2-methylcysteine residues was first achieved using a newly developed coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate (CIP). The effectiveness of CIP for the coupling of α,α-dialkyl amino acids and the reaction pathway of the activation were clarified by the syntheses of model peptides containing an α,α-dimethylamino acid. A practical method of asymmetric synthesis of 2-methylcysteine by alkylation of 2,4-cis-oxazolidinone 23 has also been described.

Chemical Synthesis of Natural Product Peptides: Coupling Methods for the Incorporation of Noncoded Amino Acids into Peptides

“…Carpino's HATU reagent (Chart ) also gives excellent results for Aib couplings and has the advantage over the amino acid fluorides of being commercially available and enabling one-pot coupling protocols. HATU permits the linkage of adjacent Aib residues in quantitative yield, whereas HOBt protocols give less than satisfactory results. , Another similarly based method is CIP (Chart ) in the presence of additive HOAt, which mediates solution phase Aib couplings in good to excellent yield (82−90% for Z-Aib-Aib-OMe). , The yields for these couplings in the absence of HOAt were comparable with those obtained from PyBrop (10−60%), but the additive HOAt improved them dramatically …”

Epimerization in peptide thioester condensation

“…The excess reagent was removed by evaporation under a stream of Ar gas. The resulting slurry was dissolved in CH 2 Cl 2 , filtered through a cotton plug, and subjected to GC on an L‐Val‐coated capillary CHROMPACK™ column . The sample was eluted with a temperature gradient.…”

Peptide Synthesis

“…Interestingly, it has been reported that in the synthesis of analogs of mosapride [329] CDI was more efficient than 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (EDC). The imidazolium reagent BOI 74 and its precursor CIP 75 were developed by Kisos group [331]. The imidazolium reagent BOI 74 and its precursor CIP 75 were developed by Kisos group [331].…”