A Versatile Chemoenzymatic Synthesis for the Discovery of Potent Cryptophycin Analogs was written by Schmidt, Jennifer J.;Khatri, Yogan;Brody, Scott I.;Zhu, Catherine;Pietraszkiewicz, Halina;Valeriote, Frederick A.;Sherman, David H.. And the article was included in ACS Chemical Biology in 2020.Formula: C4H5IN2 This article mentions the following:
The cryptophycins are a family of macrocyclic depsipeptide natural products that display exceptionally potent antiproliferative activity against drug-resistant cancers. Unique challenges facing the synthesis and derivatization of this complex group of mols. motivated us to investigate a chemoenzymic synthesis designed to access new analogs for biol. evaluation. The cryptophycin thioesterase (CrpTE) and the cryptophycin epoxidase (CrpE) are a versatile set of enzymes that catalyze macrocyclization and epoxidation of over 20 natural cryptophycin metabolites. Thus, we envisioned a drug development strategy involving their use as standalone biocatalysts for production of unnatural derivatives Herein, we developed a scalable synthesis of 12 new unit A-B-C-D linear chain elongation intermediates containing heterocyclic aromatic groups as alternatives to the native unit A benzyl group. N-Acetyl cysteamine activated forms of each intermediate were assessed for conversion to macrocyclic products using wild type CrpTE, which demonstrated the exceptional flexibility of this enzyme. Semipreparative scale reactions were conducted for isolation and structural characterization of new cryptophycins. Each was then evaluated as a substrate for CrpE P 450 and its ability to generate the epoxidized products from these substrates that possess altered electronics at the unit A styrenyl double bond position. Finally, biol. evaluation of the new cryptophycins revealed a des-β-epoxy analog with low picomolar potency, previously limited to cryptophycins bearing epoxide functionality. In the experiment, the researchers used many compounds, for example, 5-Iodo-1-methyl-1H-pyrazole (cas: 34091-51-5Formula: C4H5IN2).
5-Iodo-1-methyl-1H-pyrazole (cas: 34091-51-5) belongs to iodide derivatives. Organoiodine compounds occur widely in organic chemistry, but are relatively rare in nature. A typical method for synthesis of aromatic iodides is diazotization of primary aromatic amines followed by treatment of potassium iodide. Aliphatic alcohols are converted to alkyl iodides by treating with hydrogen iodide.Formula: C4H5IN2
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com