Computation-Assisted Disconnection Approach for the Synthesis of Neoantimycins, 15-Membered Macrocyclic Depsipeptides

Title:Computation-Assisted Disconnection Approach for the Synthesis of Neoantimycins, 15-Membered Macrocyclic Depsipeptides

Volume: 14 Issue: 2

Author(s): Shuhei Yamakoshi, Masako Okamoto, Hiroaki Sawamoto, Yuuki Arai, Eiji Kawanishi, Michiko Sasaki and Kei Takeda*

Affiliation:

• Department of Synthetic Organic Chemistry, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553,Japan

Keywords: Neoantimycin, Prunustatin A, Macrocyclization, DFT calculation, MD simulation.

Abstract: Objective: The objective of this study was to provide experimental chemists with useful guidance for proper choice of a reasonable cyclization precursor in macrolactonization in which there are several options in disconnection analysis.

Method: A combination of DFT calculations and MD simulations was used to achieve the aim. In the former method, (1) structures having a local minimum energy near the macrocyclic structure are located by DFT calculations starting from coordinates generated by breaking the corresponding ester C–O bonds (2) among the structures obtained, the one with the shortest distance between the carbon and oxygen atoms and the carboxylic carbon atom is selected as the most likely candidate for macrolactonization. The latter approach involves that (1) global minimum structures for the possible macrocyclization precursors are located by molecular mechanics calculations (2) each of the structures is subjected to MD simulations and a structure maintaining the shortest distances between the two reacting centers during the simulations is selected as a reasonable cyclization precursor.

Results: The utility of the computation-assisted disconnection approach was verified by the synthesis of prunustatin A, whose synthesis has already been reported by us, and demonstrated by the application to the synthesis of neoantimycin, a 15-membered macrocyclic depsipeptide.

Conclusion: It was demonstrated that the approach provides useful guidance for designing synthetic strategies for synthetic chemists because of the relatively high speed and simplicity of the calculations involved.

Cite this article as:

Yamakoshi Shuhei, Okamoto Masako, Sawamoto Hiroaki, Arai Yuuki, Kawanishi Eiji, Sasaki Michiko and Takeda Kei*, Computation-Assisted Disconnection Approach for the Synthesis of Neoantimycins, 15-Membered Macrocyclic Depsipeptides, Current Organic Synthesis 2017; 14 (2) . https://dx.doi.org/10.2174/1570179413666160624105401

DOI https://dx.doi.org/10.2174/1570179413666160624105401	Print ISSN 1570-1794
Publisher Name Bentham Science Publisher	Online ISSN 1875-6271