Method Yamaguchi

Use of 2,4,6-trichlorobenzoyl chloride, Et3N, and DMAP, known as the Yamaguchi method,128 is frequently used to effect macrolactonization. The reaction is believed to involve formation of the mixed anhydride with the aroyl chloride, which then forms an acyl pyridinium ion on reaction with DMAP.129... 

Notes (a) Loaded with the Yamaguchi method, (b) Fmoc-amino acid loaded with DIC/ DMAP, deprotected and reacted with bromo-acid. (c) Symmetric diamine loaded on the nitrophenyl carbonate derivative of Wang resin and subsequently reacted with bromo-acid. (d) Piperazine carboxamide scaffold reacted with the nitrophenyl carbonate derivative of Wang resin. 

Kochetkov and coworkers synthesized erythronolides A (20) and B (21) via a different route [26,27,28]. There have been many reports on the syntheses of erythromycin. Among them, four examples are the Yonemitsu synthesis of erythronolide A (20) [29,30], featuring an extremely efficient macrocyclization (the modified Yamaguchi method) Martin s synthesis of erythromycin B (19) [31,32] Evans synthesis of 6-deoxyerythronolide B [33,34], featuring the aldol-based assemblage of each synthetic segment and the Carreira synthesis of erythronolide A (20), featuring the Mg-mediated cycloadditions of nitrile oxides [35]. 

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Yamaguchi s methynolide synthesis is based on the coupling of the C1-C7 (13) and Cg-Cii (14) segments, both of which are prepared from the resolved compounds, and the macrolactonization using the mixed anhydride prepared by use of 2,4,6-trichlorobenzoyl chloride and dimethylaminopyridine (Yamaguchi method). 

Verbalactone 139 is a novel C2 symmetric macrocycUc dilactone, isolated from the roots of Verhascum undulatum possessing antibacterial activity [95]. It has 1,7-dioxacyclododecane moiety in its ring system and its first chemical total synthesis was reported by Sharma and Reddy [96] The two appropriately protected segments, acid 135 and alcohol 136, were prepared as shown in Scheme 6.23 and coupled by esterification and macrolactonization by the Yamaguchi method. 

Also, the stereoisomers of A22E and the saturated 24-methyl-26-hydroxy steroids 87.8—87.11 (Figure 87) were prepared by Claisen rearrangement and the relative stereochemistries threo or erythro) were deduced by comparison of and C NMR spectra (see Table 10) and application of the Yasunara— Yamaguchi method that established the configuration at C-25. 

---