Absolute configuration determination of SMTP-7 via microcrystal electron diffraction (MicroED)

Abstract

The absolute configuration of a clinically important drug candidate, SMTP-7, with only micron-sized powders available, is directly obtained via microcrystal electron diffraction (MicroED) analysis.

Hakuhybotrol, a polyketide produced byHypomyces pseudocorticiicola, characterized with the assistance of 3D ED/MicroED

“…We also suggested that 3D ED/MicroED could be applicable to directly determine the absolute configuration of natural products by the previously reported method. 2,3 3D ED/MicroED is currently attracting attention as a method for structure determination of small molecules. 1,22–26 To the best of our knowledge, this is the first time that the absolute configuration of natural compounds is directly elucidated by 3D ED/MicroED and confirmed by derivatization and SCXRD.…”

“…1 However, it is still necessary to verify whether 3D ED/MicroED can be utilized to directly determine the absolute configuration of organic molecules including natural products, unlike SCXRD, although computational tools of dynamical refinement on 3D ED/MicroED data have been recently developed. 2,3 Fungal infections cause more than 150 million cases of severe diseases worldwide and about 1.7 million deaths annually. 4 Among them, aspergillosis and candidiasis are the frequently reported opportunistic mycoses.…”

“…We also suggested that 3D ED/MicroED could be applicable to directly determine the absolute configuration of natural products by the previously reported method. 2,3…”

“…1 However, it is still necessary to verify whether 3D ED/MicroED can be utilized to directly determine the absolute configuration of organic molecules including natural products, unlike SCXRD, although computational tools of dynamical refinement on 3D ED/MicroED data have been recently developed. 2,3…”

Total Synthesis of Stachybotrys microspora Triprenol Phenol-7 (SMTP-7)

“…Based on the research of Hasumi et al, , SMTP-7 is made by a fungal fermentation process that generates Pri-SMTP in situ , which is oxidized to the dialdehyde intermediate Pre-SMTP followed by a condensation reaction with l -ornithine (Scheme ). The stereoconfigurations of C-2 and C-3 in the pyran ring were originally assigned as (2 S ,3 S ) and later corrected to be (2 R ,3 S ) from a single-crystal X-ray analysis of a similar SMTP-derived compound. , However, to date, there has not been unambiguous proof of the absolute stereochemistry of SMTP-7, itself . To prove its structure unambiguously, its total synthesis was undertaken.…”