First asymmetric total synthesis of aspergillide D

Abstract

The first asymmetric total synthesis of a 16-membered macrolide, aspergillide D, is described. The chiral centers of the acid are derived from d-ribose and the alcohol subunit from 1,8-octane diol through Sharpless kinetic resolution, respectively. The other key reactions include Yamaguchi esterification, ring-closing metathesis reaction, and Shiina macrolactonization to construct the fully functionalized macrocycle.

Marine natural products

“…270) and asymmetric total synthesis of the azaphilone derivative felinone A (Beauveria felina) resulted in revision of the absolute conguration to 737. 271 Asymmetric total synthesis of aspergillide D, a 16-membered macrolide originally obtained from a gorgonian-derived Aspergillus sp., was achieved using a convergent strategy, 272 while synthesis of the tetramic acid derivative cladosin C (Cladosporium sphaerospermum) was achieved starting with inexpensive, commercially available compounds. 273 The dimeric trans-epoxyamide, chrysamide B (Penicillium chrysogenum) was synthesised utilising a convergent approach 274 and a parallel synthetic approach was used to achieve synthesis of the 1,4-benzoquinones anserinones A and B (Penicillium spp.).…”

A 26-Membered Macrocycle Obtained by a Double Diels–Alder Cycloaddition Between Two 2H-Pyran-2-one Rings and Two 1,1'-(Hexane-1,6-diyl)bis (1H-pyrrole-2,5-dione)s

“…1 H NMR spectra were recorded at 29 °C with a Bruker Avance III 500 spectrometer at 500 MHz using Me 4 Si as an internal standard. 13 C NMR spectra were recorded at 29 °C with a Bruker Avance III 500 spectrometer at 125 MHz and were referenced against the central line of the solvent signal (CDCl 3 triplet at 77.0 ppm or DMSO-d 6 septet at 39.5 ppm).…”

“…3 There were many successful attempts towards the preparation of macrocycles, one of the most-often used being dilution techniques triggering the macrocyclization via lactonization, lactamization, metathesis reaction etc. (that were recently used for the first asymmetric total synthesis of aspergillide D 4 or for the total synthesis of mandelalide A). 5 Other options include the template-induced cyclization (around the host ion) 6 and cyclization on a solid support (like Merrifield-based synthesis of cyclic peptides or such inspired by non-ribosomal peptide aldehydes).…”

“…9 However, even this approach is generally applied just to obtain the requisite linear precursors that are latter assembled via a suitable ring-closing reaction into the final macrocyclic target. [10][11][12][13][14] Of interest are also preparations of calix [4]arene systems linked with 1,2,4-triazole and 1,3,4-oxadiazole derivatives, 15 as well as other tetraaza macrocycles applied as ligands in various coordination compounds. 16 Herein we present another approach, where two double Diels-Alder cycloadditions between two molecules of the substituted 2H-pyran-2-ones (each acting as a "double" diene) 17 and two molecules of the double dienophile provide a 26-membered tetraaza macrocyclic system.…”

Stereoselective synthesis of marine macrolide Aspergillide D

“…The structural confirmation by 1 H, 13 C NMR, NOESY, HRMS-ESI and DEPT spectral analysis was performed by the Qi group. 3 The first asymmetric synthesis of aspergillide D was reported by Mohapatra et al 4…”