Transannular O-Heterocyclization: A Useful Tool for the Total Synthesis of Murisolin and 16,19-cis-Murisolin

Abstract

Transannular O-heterocyclization is applied as a key step in a total synthesis. This highly stereoselective and metal-free transformation introduces four stereocenters in one step. It was chosen to be the pivotal step in the synthesis of Murisolin and 16,19-cis-Murisolin, two annonaceous acetogenins. The efficiency of this synthesis is further illustrated by a stereodivergent late-stage separation of both synthetic routes.

Recent Advances in Total Synthesis via Metathesis Reactions

“…Despite the excellent functional group tolerance and the low sensitivity to steric hindrances displayed by these catalysts, we can find in the literature numerous examples in which steric factors appear to play a crucial role in unsuccessful ring-closure reactions. This is the case for compound 105, which was devised as a potential precursor for the synthesis of the natural product pseudotabersonine (106) by Martin and co-workers (Scheme 9). 91 Thus, when 105 was treated with different ruthenium catalysts, including Grubbs I (3), Grubbs II (4), H-G II (6), or even the Grubbs-Stewart catalyst (12), which is especially reactive towards sterically hindered olefins, the desired product 107, resulting from a double RCM process was not observed, instead obtaining the monocyclized product 108 in moderate yields, together with degradation products.…”

“…Within the field of total synthesis, several interesting syntheses of natural products have been reported in which the CM represented the key step for the coupling of the important fragments of the molecule, thus allowing the completion of the synthesis. Among the most outstanding contributions of the last few years are the total syntheses of the fluorinated cryptophycin (155), 104 FD-891 (156), 105 murisolin (157), 106 ledoglucomides A (158) and B (159), 107 epicoccamide D (160), 108 synargentolide B (161), 109 homaline (162), 110 bitungolide F (163), 111 penarolide (164), 112 cytospolide D (165), 113 goniocin (166), 114 cryptomoscatone F1 167, 115 curvicollide C (168), 116 proposed structures for cryptorigidifoliol K 169a-d, 117 and alotaketal A (170) 118 ( Figure 6).…”

Recent advances of desymmetrization protocol applied in natural product total synthesis

“…16b In 2012, Haufe group developed a novel Lego-like building block strategy toward the total synthesis of 26 and 27 in 1.6% or 0.2% overall yields. 17 In their strategy, desymmetrization of inseparable diols 28a, b mixture, gave a 62:38 mixture of intermediates 29a (96% ee) and 29b (76% ee) by using Candida rugosa lipase and vinyl acetate (Scheme 9).…”

Stereoselective Total Synthesis of (+)‐Giganin and Its C10 Epimer by Using Late‐Stage Lithiation–Borylation Methodology

“…A common strategy towards this family of molecules has been to first add a functional group (an alkene) somewhere between the remote hydroxy groups and then to use it to aid disconnection. [6][7][8][9] However, this is wasteful as the functional group has to be introduced and then removed at the end. An alternative approach would be to disconnect the molecule directly at a secondary alcohol as this would not only enable C À C bond formation but also potentially control stereochemistry in the process.…”