Determination of the full structure and absolute stereochemistry of the antifungal agent FR-900848: an X-ray crystallographic study of (1R,3S,4R,6S,7S,9R,10S,12R)-quatercyclopropyl-1,12-dimethanediyl di-4-bromobenzoate

Abstract

Degradation studies and partial synthesis are used t o establish the full structure and absolute stereochemistry of the nucleoside antifungal agent FR-900848.

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

“…These conformations must result from energetic compromises between intramolecular van der Waals interactions between hydrogen atoms or simply from crystal packing effects. It is noteworthy that such a conformation has never been observed in the solid state for either of the quater‐ or quinquecyclopropane derivatives along the routes to FR‐900848 ( 1 ) (all‐ gauche conformation10b, 12) and to U‐106305 ( 2 ) ( gauche / trans / gauche / gauche conformation13c), or the macrocyclic compounds containing a quinquecyclopropane fragment (predominating trans / trans / gauche / trans conformation15a).…”

Assembly of the antifungal agent FR-900848 and the CETP inhibitor U-106305: studies on remarkable multicyclopropane natural products

“…Likewise, use of dioxaborolane 13 gave the quatercyclopropane 41 (100%). It was apparent from 1 H and 13 C NMR data that the quatercyclopropanes 40 and 41 were two different C 2 -symmetric isomers, and we rigourously established structures by an X-ray crystallographic study 25 of the bis(4bromobenzoate) ester derived from 40 (Fig. 2).…”

“…We have explored three strategies for the stereoselective construction of quatercyclopropane arrays: (i) a double Yamamoto cyclopropanation followed by a double Charette cyclopropanation, 9,25 (ii) a double Charette cyclopropanation followed by a second double Charette cyclopropanation, 26 and (iii) a tetraene tetracyclopropanation reaction. 21 In the first approach (Scheme 7), acid catalysed hydrolysis of the diacetal 33 gave the corresponding dialdehyde, which was directly homologated using a double Wittig reaction to provide a mixture of the E,Ediester 37 and the E,Z-diester 38 (3.7 : 1).…”

“…The stereochemistry of the quatercyclopropane unit of FR-900848 1 was determined 25,32 by comparison of the acetates prepared from the model diols 40 and 41 with the corresponding degradation product 2 3 derived from the natural product. We were delighted to observe that quatercyclopropane 2 was identical in all respects, including the absolute stereochemistry, with the diacetate from diol 40.…”

Stereochemical Elucidation of the Pentacyclopropane Antifungal Agent FR-900848

“…10 Herein we report full experimental details for the structural elucidation of FR-900848 (1) which was previously reported in communication format. [11][12][13][14] These studies were an essential prerequisite for our total synthesis of FR-900848 (1) also recently reported. 15 After the communications we have published on FR-900848 (1) [11][12][13][14] and during the drafting of this paper, Kuo et al have reported on the isolation and structural determination of U-106305 (8).…”