Synthetic Approaches Towards the Total synthesis of tubulysin and its fragments: A review

Background: Tubulysins, linear tetrapeptides show extraordinary cytotoxicity against various cancer cells, with IC50 values in nano or picomolar range. Due to their extremely vigorous anti-proliferative and antiangiogenic characteristics, tubulysins exhibit captivating prospects in the development of anticancer drugs. This review focuses on diverse routes for the total synthesis of natural and synthetic tubulysins as well as their fragments. Objective: The purpose of this review is to present the synthetic strategies for the development of antitumor agents, tubulysins. Conclusion: A range of synthetic pathways adopted for the total synthesis of tubulysins and their fragments have been described in this review. Synthesis of fragments, Tuv, Tup, and Tut can be accomplished by adopting appropriate strategies such as Manganese-mediated synthesis, Ireland-Claisen rearrangement, Mukaiyama aldol reaction, and Mannich process etc. Tubulysin B, D, U, V, and N14-desacetoxytubulysin H have been prepared through Mitsunobu reaction, tert-butanesulfinamide method, Tandem reaction, aza-Barbier reaction, Evans aldol reaction, and C-H activation strategies etc. The remarkable anticancer potential of tubulysins toward a substantiate target make them prominent leads for developing novel drugs against multidrug-resistant cancers.

An Example of Ketone Olefination via Praseodymium-Mediated Barbier Reaction in the Presence of Diethyl Phosphite

The first example of carbon double-bond formation via praseodymium-mediated Barbier type reaction of ketones and allyl halides in the presence of diethyl phosphite is reported. The reaction is highly α-regioselective and conveniently carried out under mild conditions in a one-pot fashion. From a synthetic point of view, a series of conjugated alkenes were obtained in moderate to good yields in this one-pot reaction with practical reaction conditions.

The Role Ionic Liquid [BMIM][PF6] in One-Pot Synthesis of Tetrahydropyran Rings through Tandem Barbier–Prins Reaction

Tetrahydropyran (THP) rings are common in several natural products, therefore, various strategies are being developed to synthesize these rings. The present work described the study of a one-pot synthesis of 2,4,6-trisubstituted tetrahydropyran compounds promoted by the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6] through a Barbier–Prins reaction between allyl bromide and aldehydes. The use of [BMIM][PF6] gave Prins products from several aldehydes in good yields and reaction times. We also found that the anion, PF6-, accelerates the Barbier reaction when used alone, and the excess SnBr2 from the reaction conditions of the Barbier reaction leads to the formation of the THP rings, thus acting as a catalyst for Prins cyclization. Additionally, we demonstrate that ionic liquid can be recovered and reused five times in the preparation of 4-bromo-tetrahydro-2,6-diphenyl-2H-pyran without significant yield loss.

Modeling and Molecular Dyanamics Simulations Study of Enol-carbonates and their Derivatives

In view of the fact that the mechanisms of the interaction of organic molecules with the properties of the drug occur in most cases by their binding to the receptors (proteins), we wanted to examine the interactions of small organic molecules that we synthesized and certain proteins. In this paper the comparison between molecules, modeled by different software packages, and experimental results is performed. The series of new molecules are synthesized using Barbier reaction of allylation of carbonyl compounds with 4-(bromomethyl)-1,3-dioxol-2-one as a highly fictionalized allylic synthon. Their structure was determined by spectroscopic methods (NMR-, IR- and UV/VIS-spectroscopy and MS-spectrometry), while for three individual molecules analysis of x-ray diffraction (X-ray analysis) was also performed, which gave the final confirmation of the exact arrangement of all atoms in the space. The molecules are represented in standard chemical format, visualized and prepared for simulations. In order to obtain datasets that further can be used to examine and analyze interactions with well-known proteins, molecular dynamic simulations are performed. The purpose of this research was to present that using powerful computer infrastructure and appropriate software tools, an accurate molecule models can be created.

Photocatalytic Barbier reaction – visible-light induced allylation and benzylation of aldehydes and ketones

We report a photocatalytic version of the Barbier type reaction using readily available allyl or benzyl bromides and aromatic aldehydes or ketones as starting materials to generate allylic or benzylic alcohols.